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Search for "diol" in Full Text gives 384 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis
- Prodip Howlader and
- Michael Schmittel
Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62
- enantioselectivity (94% ee). Using similar reaction conditions, the non-assembled BINOL derivative (S)-3,3'-dibromo-[1,1'-binaphthyl]-2,2'-diol acted as a superior catalyst (99% yield) but achieved a lower enantioselectivity (84% ee). Therefore, this result indicates that the incorporation of multiple catalytic
Graphical Abstract
Figure 1: Butterfly 1 (Figure was reprinted with permission from [45]. Copyright 2012 American Chemical Society. ...
Figure 2: Synthesis of the three-component heteroleptic molecular boat 8 and its use as a catalyst for the Kn...
Figure 3: Synthesis of the two-component triangle 14 and three-component heteroleptic prism 15 [59]. Figure was a...
Figure 4: Catalytic Michael addition reaction using the urea-decorated molecular prism 15 [59].
Figure 5: Self-assembly of two-component tetragonal prismatic architectures with different cavity size. Figur...
Figure 6: Construction of artificial LHS using rhodamine B as an acceptor and 24b as donor generating a photo...
Figure 7: Synthesis of supramolecular spheres with varying [AuCl] concentration inside the cavity. Figure was...
Figure 8: Hydroalkoxylation reaction of γ-allenol 34 in the presence of [AuCl]-encapsulated molecular spheres ...
Figure 9: Two-component heteroleptic triangles of different size containing a BINOL functionality. Figure was...
Figure 10: Asymmetric conjugate addition of chalcone 42 with trans-styrylboronic acid (43) catalyzed by BINOL-...
Figure 11: Encapsulation of monophosphoramidite-Rh(I) catalyst into a heteroleptic tetragonal prismatic cage 47...
Figure 12: (a) Representations of the basic HETPYP, HETPHEN, and HETTAP complex motifs. (b) The three-componen...
Figure 13: Two representative four-component rotors, with a (top) two-arm stator and (bottom) a four-arm stato...
Figure 14: Four-component rotors with a monohead rotator. Figure was adapted with permission from [94]. Copyright ...
Figure 15: (left) Click reaction catalyzed by rotors [Cu2(55)(60)(X)]2+. (right) Yield as a function of the ro...
Figure 16: A supramolecular AND gate. a) In truth table state (0,0) two nanoswitches serve as the receptor ens...
Figure 17: Two supramolecular double rotors (each has two rotational axes) and reference complex [Cu(78)]+ for...
Figure 18: The slider-on-deck system (82•X) (X = 83, 84, or 85). Figure is from [98] and was reprinted from the jo...
Figure 19: Catalysis of a conjugated addition reaction in the presence of the slider-on-deck system (82•X) (X ...
Figure 20: A rotating catalyst builds a catalytic machinery. For catalysis of the catalytic machinery, see Figure 21. F...
Figure 21: Catalytic machinery. Figure was adapted from [100] (“Evolution of catalytic machinery: three-component n...
Figure 22: An information system based on (re)shuffling components between supramolecular structures [99]. Figure ...
Figure 23: Switching between dimeric heteroleptic and homoleptic complex for OFF/ON catalytic formation of rot...
Figure 24: A chemically fueled catalytic system [112]. Figure was adapted from [112]. Copyright 2021 American Chemical S...
Figure 25: (Top) Operation of a fuel acid. (Bottom) Knoevenagel addition [112].
Figure 26: Development of the yield of Knoevenagel product 118 in a fueled system [112]. Figure was reprinted with ...
Figure 27: Weak-link strategy to increased catalytic activity in epoxide opening [119]. Figure was adapted from [24]. C...
Figure 28: A ON/OFF polymerization switch based on the weak-link approach [118]. Figure was reprinted with permissi...
Figure 29: A weak-link switch turning ON/OFF a Diels–Alder reaction [132]. Figure was reprinted with permission fro...
Figure 30: A catalyst duo allowing selective activation of one of two catalytic acylation reactions [133] upon subs...
Figure 31: A four-state switchable nanoswitch (redrawn from [134]).
Figure 32: Sequential catalysis as regulated by nanoswitch 138 and catalyst 139 in the presence of metal ions ...
Figure 33: Remote control of ON/OFF catalysis administrated by two nanoswitches through ion signaling (redrawn...
A study of the photochemical behavior of terarylenes containing allomaltol and pyrazole fragments
- Constantine V. Milyutin,
- Andrey N. Komogortsev,
- Boris V. Lichitsky and
- Valeriya G. Melekhina
Beilstein J. Org. Chem. 2022, 18, 588–596, doi:10.3762/bjoc.18.61
- diastereospecificity of the studied process, which leads to the formation of a trans-diastereomer (mixture of S/S- and R/R-enantiomers). The structure of vicinal diol 18 was unambiguously established by single-crystal X-ray diffraction (Figure 4). Conclusion In summary, we have studied the photochemical behavior of
Graphical Abstract
Scheme 1: Photochemical transformations of 3-hydroxypyran-4-one derivatives.
Scheme 2: Synthesis and study of the photochemical behavior of compound 16.
Scheme 3: Photoreaction of compound 12a.
Figure 1: 1H NMR monitoring of the photoreaction of compound 12a under UV irradiation (365 nm) in DMSO-d6 sol...
Scheme 4: Proposed mechanism for the photoreaction of compound 11a.
Scheme 5: Synthesis of compounds 15a–l. Reaction conditions: 1) 12a–l (0.5 mmol), AcOH (25 mL), UV irradiatio...
Figure 2: The X-ray crystal structure of compound 15a.
Scheme 6: Synthesis of compounds 15m–o. Reaction conditions: 1) 12m–o (0.5 mmol), AcOH (25 mL), UV irradiatio...
Figure 3: The X-ray crystal structure of compound 15m.
Scheme 7: Synthesis of compound 18.
Figure 4: The X-ray crystal structure of compound 18.
BINOL as a chiral element in mechanically interlocked molecules
- Matthias Krajnc and
- Jochen Niemeyer
Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53
- '-binaphthyl-2,2'-diol (BINOL) unit as a stereogenic element in mechanically interlocked molecules (MIMs). We describe the synthesis and properties of such BINOL-based chiral MIMs, together with their use in further diastereoselective modifications, their application in asymmetric catalysis, and their use in
- planar chirality into at least one of the subcomponents. One of the most important chiral molecular frameworks in general is the 1,1'-binaphthyl-2,2'-diol unit (BINOL, see Figure 1). BINOL is an axially chiral molecule with a high configurational stability and a well-established synthetic chemistry
Graphical Abstract
Figure 1: Molecular structures of (R)-BINOL (left) and (S)-BINOL (right).
Figure 2: Synthesis of Sauvage´s [2]catenanes (S,S)-5 and (S,S)-6 containing two BINOL units by the passive m...
Figure 3: Synthesis of Saito´s [2]rotaxane (R)-10 from a BINOL-based macrocycle by the active metal template ...
Figure 4: Synthesis of Stoddart´s [2]rotaxane (rac)-14 by an ammonium crown ether template.
Figure 5: Synthesis of Stoddart´s BINOL-containing [2]catenanes 18/20/22/24 by π–π recognition.
Figure 6: Synthesis of Takata´s rotaxanes featuring chiral centers on the axle: a) rotaxane (R,R,R/S)-27 obta...
Figure 7: Takata´s chiral polyacetylenes 32/33 featuring BINOL-based [2]rotaxane side chains.
Figure 8: Synthesis of Takata´s chiral thiazolium [2]rotaxanes (R)-35a/b and (R)-38.
Figure 9: Results for the asymmetric benzoin condensation of benzaldehyde (39) with catalysts (R)-35a/b and (R...
Figure 10: Synthesis of Takata´s pyridine-based [2]rotaxane (R)-42.
Figure 11: The asymmetric desymmetrization reaction of meso-1,2-diols with rotaxane (R)-42.
Figure 12: Synthesis of Niemeyer´s axially chiral [2]catenane (S,S)-47.
Figure 13: Results for the enantioselective transfer hydrogenation of 2-phenylquinoline with catalysts (S,S)-47...
Figure 14: Synthesis of Niemeyer´s chiral [2]rotaxanes (S)-56/57.
Figure 15: Results for the enantioselective Michael addition with different rotaxane catalysts (S)-56a/56b/57a/...
Figure 16: Synthesis of Beer´s [2]rotaxanes 64a/b for anion recognition.
Figure 17: Association constants of different anions (used as the Bu4N+ salts) to the [2]rotaxanes (S)-64a/b a...
Figure 18: Synthesis of Beer´s [3]rotaxane (S)-68.
Figure 19: Association constants of different anions (used as the Bu4N+-salts) to the [2]rotaxane (S)-68 and a...
The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban
- Martin Vrbický,
- Karel Macek,
- Jaroslav Pochobradský,
- Jan Svoboda,
- Miloš Sedlák and
- Pavel Drabina
Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46
- -1,2-diol, etc.) [11]. Beside this, approaches in which asymmetric synthesis is included are also applicable. Recently, the utilization of an asymmetric Henry reaction for the preparation of two oxazolidine-type drugs, namely linezolid (1) and rivaroxaban (2), has been described [12][13]. These
Graphical Abstract
Figure 1: The structure of the oxazolidine-2-one-containing drugs linezolid (1) and rivaroxaban (2).
Figure 2: Overview of the chiral ligands that were used for the study of the asymmetric Henry reaction.
Scheme 1: Syntheses of aldehydes 15–20.
Scheme 2: Synthesis of linezolid (1) and rivaroxaban (2) from nitroaldols 24 or 26.
Menadione: a platform and a target to valuable compounds synthesis
- Acácio S. de Souza,
- Ruan Carlos B. Ribeiro,
- Dora C. S. Costa,
- Fernanda P. Pauli,
- David R. Pinho,
- Matheus G. de Moraes,
- Fernando de C. da Silva,
- Luana da S. M. Forezi and
- Vitor F. Ferreira
Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43
Graphical Abstract
Figure 1: Natural bioactive naphthoquinones.
Figure 2: Chemical structures of vitamins K.
Figure 3: Redox cycle of menadione.
Scheme 1: Selected approaches for menadione synthesis using silver(I) as a catalyst.
Scheme 2: Methylation approaches for the preparation of menadione from 1,4-naphthoquinone using tert-butyl hy...
Scheme 3: Methylation approach of 1,4-naphthoquinone using i) rhodium complexes/methylboronic acid and ii) bi...
Scheme 4: Synthesis of menadione (10) from itaconic acid.
Scheme 5: Menadione synthesis via Diels–Alder reaction.
Scheme 6: Synthesis of menadione (10) using p-cresol as a synthetic precursor.
Scheme 7: Synthesis of menadione (10) via demethoxycarbonylating annulation of methyl methacrylate.
Scheme 8: Furan 34 used as a diene in a Diels–Alder reaction for the synthesis of menadione (10).
Scheme 9: o-Toluidine as a dienophile in a Diels–Alder reaction for the synthesis of menadione (10).
Scheme 10: Representation of electrochemical synthesis of menadione.
Figure 4: Reaction sites and reaction types of menadione as substrate.
Scheme 11: DBU-catalyzed epoxidation of menadione (10).
Scheme 12: Phase-transfer catalysis for the epoxidation of menadione.
Scheme 13: Menadione epoxidation using a hydroperoxide derived from (+)-norcamphor.
Scheme 14: Enantioselective Diels–Alder reaction for the synthesis of asymmetric quinone 50 catalyzed by a chi...
Scheme 15: Optimized reaction conditions for the synthesis of anthra[9,1-bc]pyranone.
Scheme 16: Synthesis of anthra[9,1-bc]furanone, anthra[9,1-bc]pyridine, and anthra[9,1-bc]pyrrole derivatives.
Scheme 17: Synthesis of derivatives employing protected trienes.
Scheme 18: Synthesis of cyclobutene derivatives of menadione.
Scheme 19: Menadione reduction reactions using sodium hydrosulfite.
Scheme 20: Green methodology for menadiol synthesis and pegylation.
Scheme 21: Menadione reduction by 5,6-O-isopropylidene-ʟ-ascorbic acid under UV light irradiation.
Scheme 22: Selected approaches of menadione hydroacetylation to diacetylated menadiol.
Scheme 23: Thiele–Winter reaction catalyzed by Bi(OTf)3.
Scheme 24: Carbonyl condensation of menadione using resorcinol and a hydrazone derivative.
Scheme 25: Condensation reaction of menadione with thiosemicarbazide.
Scheme 26: Condensation reaction of menadione with acylhydrazides.
Scheme 27: Menadione derivatives functionalized with organochalcogens.
Scheme 28: Synthesis of selenium-menadione conjugates derived from chloromethylated menadione 84.
Scheme 29: Menadione alkylation by the Kochi–Anderson method.
Scheme 30: Menadione alkylation by diacids.
Scheme 31: Menadione alkylation by heterocycles-substituted carboxylic acids.
Scheme 32: Menadione alkylation by bromoalkyl-substituted carboxylic acids.
Scheme 33: Menadione alkylation by complex carboxylic acids.
Scheme 34: Kochi–Anderson method variations for the menadione alkylation via oxidative decarboxylation of carb...
Scheme 35: Copper-catalyzed menadione alkylation via free radicals.
Scheme 36: Nickel-catalyzed menadione cyanoalkylation.
Scheme 37: Iron-catalyzed alkylation of menadione.
Scheme 38: Selected approaches to menadione alkylation.
Scheme 39: Menadione acylation by photo-Friedel–Crafts acylation reported by Waske and co-workers.
Scheme 40: Menadione acylation by Westwood procedure.
Scheme 41: Synthesis of 3-benzoylmenadione via metal-free TBAI/TBHP system.
Scheme 42: Michael-type addition of amines to menadione reported by Kallmayer.
Scheme 43: Synthesis of amino-menadione derivatives using polyalkylamines.
Scheme 44: Selected examples for the synthesis of different amino-substituted menadione derivatives.
Scheme 45: Selected examples of Michael-type addition of complex amines to menadione (10).
Scheme 46: Addition of different natural α-amino acids to menadione.
Scheme 47: Michael-type addition of amines to menadione using silica-supported perchloric acid.
Scheme 48: Indolylnaphthoquinone or indolylnaphthalene-1,4-diol synthesis reported by Yadav et al.
Scheme 49: Indolylnaphthoquinone synthesis reported by Tanoue and co-workers.
Scheme 50: Indolylnaphthoquinone synthesis from menadione by Escobeto-González and co-workers.
Scheme 51: Synthesis of menadione analogues functionalized with thiols.
Scheme 52: Synthesis of menadione-derived symmetrical derivatives through reaction with dithiols.
Scheme 53: Mercaptoalkyl acids as nucleophiles in Michael-type addition reaction to menadione.
Scheme 54: Reactions of menadione (10) with cysteine derivatives for the synthesis of quinoproteins.
Scheme 55: Synthesis of menadione-glutathione conjugate 152 by Michael-type addition.
Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues
- Sandeep Kumar,
- Jyotirmoy Maity,
- Banty Kumar,
- Sumit Kumar and
- Ashok K. Prasad
Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10
- its extraction in the organic phase during work up procedure. So, the classical chemical route to synthesize nucleosides 9a,b started with the conversion of diacetone ᴅ-glucofuranose 10 to 3′-azido-3′-deoxy-β-ᴅ-allofuranoside 11, which on acidification with 80% acetic acid gave furanoside diol 17. The
- regioselective protection of the primary hydroxy group of diol 17 using TBDPS-Cl in pyridine at room temperature afforded TBDPS-protected furanoside 18, which on acetolysis using AcOH/Ac2O/H2SO4 (100:10:0.1) afforded the anomeric mixture of coupling sugar 19a,b in 80% yield. The Vorbrüggen coupling [29] of
Graphical Abstract
Figure 1: Structure of AZT and representative related bicyclic nucleosides.
Scheme 1: Retrosynthetic routes for the synthesis of (5′R)-3′-azido-3′-deoxy-2′-O,5′-C-bridged-β-ᴅ-homoarabin...
Scheme 2: Synthesis of 3′-azido-3′-deoxy-β-ᴅ-allofuranosylthymine (14a) and -uracil (14b).
Scheme 3: Biocatalytic acetylation of the primary hydroxy group of nucleosides 14a,b.
Scheme 4: Synthesis of (5'R)-3′-azido-3′-deoxy-2′-O,5′-C-bridged-β-ᴅ-homoarabinofuranosyl nucleosides 9a,b.
Scheme 5: Chemical synthesis of nucleosides 9a,b starting from diacetone ᴅ-glucofuranose.
Figure 2: Structure elucidation of (5′R)-3′-azido-3′-deoxy-2′-O,5′-C-bridged-β-ᴅ-homoarabinofuranosylthymine (...
Scheme 6: a) Plausible mechanism for the synthesis of (5′R)-3′-azido-3′-deoxy-2′-O,5′-C-bridged-β-ᴅ-homoarabi...
Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives
- İlknur Polat,
- Selçuk Eşsiz,
- Uğur Bozkaya and
- Emine Salamci
Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7
- diol 5 as a single isomer in 91% yield. We assume that the trans selectivity of hydroxylation in ester 4 is due to the steric effect of the presence of the bulky Boc group. The structure of 5 was determined with the help of 1D (1H and 13C) and 2D (COSY and HMQC) NMR spectra. The diagonal peak at 4.10
- expected product 9 failed. The product 8 was obtained as the major product in 80% yield, and the expected product 9 was formed as the minor product in 4% yield. We propose that diol isomer mixture 9 can be formed by solvolysis. The presence of the lactone ring in 8 was determined by 2D NMR spectroscopic
- a mixture of products 10 and 11 in a 7:3 ratio was determined by NMR spectroscopy. The reaction mixture was purified using preparative silica gel TLC on a chromatotron with ethyl acetate/hexane (50:50) as the eluent to give carbamate 10 and diol isomer mixture 11 in 65% and 25% yields, respectively
Graphical Abstract
Figure 1: Examples of natural products containing β-amino acids.
Scheme 1: Synthesis of cyclic β-amino acid 6.
Scheme 2: Epoxidation of Boc-protected amino ester 4 and hydrolysis of epoxide 7 with HCl(g)–MeOH.
Scheme 3: Reaction of epoxide 7 with NaHSO4 in methylene chloride/MeOH.
Figure 2: The X-ray crystal structure of 10.
Scheme 4: Synthesis of cyclic β-amino acid derivative 8.
Scheme 5: Suggested mechanism for the reaction of epoxide 7 with NaHSO4.
Figure 3: Solvent-corrected relative free energy profile at 298.15 K for the reaction mechanism of 14 shown i...
Figure 4: Solvent-corrected relative free energy profile at 298.15 K for the reaction mechanism of 17 shown i...
Figure 5: The optimized geometries of the conformers 7a and 7b with selected interatomic distances at the B3L...
Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation
- Lukáš Ďurina,
- Anna Ďurinová,
- František Trejtnar,
- Ľuboš Janotka,
- Lucia Messingerová,
- Jana Doháňošová,
- Ján Moncol and
- Róbert Fischer
Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188
- -stereoselective epoxidation of 2,3-dihydroisoxazole with in situ-generated DMDO, the syn-selective α-chelation-controlled addition of vinyl-MgBr/CeCl3 to the isoxazolidine-4,5-diol intermediate, and the substrate-directed epoxidation of the terminal double bond of the corresponding γ-amino-α,β-diol with aqueous
- cancer cell lines [14]. For this reason, the compounds 1 and 2 were prepared first in their racemic form to begin the initial biological studies. Results and Discussion The starting isoxazolidine-4,5-diol 3, possessing the desired 3,4-trans configuration (Scheme 1), will be prepared by using our
- isoxazolidine-4,5-diols in the presence of anhydrous cerium chloride [17], which proceeded in a highly syn-diastereoselective manner due to the presence of the unprotected hydroxy group in the α-position. Accordingly, the diol 3 will be examined in the reaction with vinylmagnesium bromide with an emphasis on
Graphical Abstract
Figure 1: (−)-Codonopsinol B (1) and its N-nor-methyl analogue 2; known inhibition activities against α-gluco...
Scheme 1: Synthetic approach towards (±)-codonopsinol B (1) and its N-nor-methyl analogue 2.
Scheme 2: Synthesis of isoxazolidine-4,5-diol (±)-3. Reagents and conditions: (a) ᴅʟ-proline, CHCl3, rt, 48 h...
Scheme 3: Synthesis of final pyrrolidines (±)-1 and (±)-2. Reagents and conditions: (a) vinyl-MgBr, CeCl3, TH...
Figure 2: Molecular structure of N-Cbz-protected pyrrolidine 12 confirmed by single-crystal X-ray crystallogr...
Synthetic strategies toward 1,3-oxathiolane nucleoside analogues
- Umesh P. Aher,
- Dhananjai Srivastava,
- Girij P. Singh and
- Jayashree B. S
Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182
- % aqueous sulfuric acid, the isopropylidene group of 13 was selectively deprotected at 70 °C in dioxane to obtain diol 14. This diol was further cleaved using lead tetraacetate, and further reduction with sodium borohydride produced compound 15. The 5'-hydroxy group of 15 was then treated with tert
- ). Sodium periodate was used for oxidative cleavage of cis-diol 3d. The subsequent aldehyde was then converted to a vicinal diol by reduction with sodium borohydride. Further, it was protected by 2,2-dimethoxypropane to give the 1,3-oxathiolane derivative 21. The benzoylated compound 22 was obtained by
- reaction of benzoyl chloride in pyridine to protect the hydroxy group, which results in a high yield. The isopropylidene group was selectively deprotected using 10% HCl, followed by oxidative breakage of the carbon–carbon bond of the resulting diol using sodium periodate. Further reduction of the aldehyde
Graphical Abstract
Figure 1: Representative modified 1,3-oxathiolane nucleoside analogues.
Figure 2: Mechanism of antiviral action of 1,3-oxathiolane nucleosides, 3TC (1) and FTC (2), as chain termina...
Figure 3: Synthetic strategies for the construction of the 1,3-oxathiolane sugar ring.
Scheme 1: Synthesis of 4 from benzoyloxyacetaldehyde (3a) and 2-mercapto-substituted dimethyl acetal 3na.
Scheme 2: Synthesis of 8 from protected glycolic aldehyde 3b and 2-mercaptoacetic acid (3o).
Scheme 3: Synthesis of 20 from ᴅ-mannose (3c).
Scheme 4: Synthesis of 20 from 1,6-thioanhydro-ᴅ-galactose (3d).
Scheme 5: Synthesis of 8 from 2-(tert-butyldiphenylsilyloxy)methyl-5-oxo-1,2-oxathiolane (3m).
Scheme 6: Synthesis of 20a from ʟ-gulose derivative 3f.
Scheme 7: Synthesis of 31 from (+)-thiolactic acid 3p and 2-benzoyloxyacetaldehyde (3a).
Scheme 8: Synthesis of 35a from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g) hydrate.
Scheme 9: Synthetic routes toward 41 through Pummerer reaction from methyl 2-mercaptoacetate (3j) and bromoac...
Scheme 10: Strategy for the synthesis of 2,5-substituted 1,3-oxathiolane 41a using 4-nitrobenzyl glyoxylate an...
Scheme 11: Synthesis of 44 by a resolution method using Mucor miehei lipase.
Scheme 12: Synthesis of 45 from benzoyloxyacetaldehyde (3a) and 2-mercaptoacetaldehyde bis(2-methoxyethyl) ace...
Scheme 13: Synthesis of 46 from 2-mercaptoacetaldehyde bis(2-methoxyethyl) acetal (3nc) and diethyl 3-phosphon...
Scheme 14: Synthesis of 48 from 1,3-dihydroxyacetone dimer 3l.
Scheme 15: Approach toward 52 from protected alkene 3rb and lactic acid derivative 51 developed by Snead et al....
Scheme 16: Recent approach toward 56a developed by Kashinath et al.
Scheme 17: Synthesis of 56a from ʟ-menthyl glyoxylate (3h) hydrate by DKR.
Scheme 18: Possible mechanism with catalytic TEA for rapid interconversion of isomers.
Scheme 19: Synthesis of 35a by a classical resolution method through norephedrine salt 58 formation.
Scheme 20: Synthesis of 63 via [1,2]-Brook rearrangement from silyl glyoxylate 61 and thiol 3nb.
Scheme 21: Combined use of STS and CAL-B as catalysts to synthesize an enantiopure oxathiolane precursor 65.
Scheme 22: Synthesis of 1 and 1a from glycolaldehyde dimer 64 and 1,4-dithiane-2,5-diol (3q) using STS and CAL...
Scheme 23: Synthesis of 68 by using Klebsiella oxytoca.
Scheme 24: Synthesis of 71 and 72 using Trichosporon taibachii lipase and kinetic resolution.
Scheme 25: Synthesis of 1,3-oxathiolan-5-ones 77 and 78 via dynamic covalent kinetic resolution.
Figure 4: Pathway for glycosidic bond formation.
Scheme 26: First synthesis of (±)-BCH-189 (1c) by Belleau et al.
Scheme 27: Enantioselective synthesis of 3TC (1).
Scheme 28: Synthesis of cis-diastereomer 3TC (1) from oxathiolane propionate 44.
Scheme 29: Synthesis of (±)-BCH-189 (1c) via SnCl4-mediated N-glycosylation of 8.
Scheme 30: Synthesis of (+)-BCH-189 (1a) via TMSOTf-mediated N-glycosylation of 20.
Scheme 31: Synthesis of 3TC (1) from oxathiolane precursor 20a.
Scheme 32: Synthesis of 83 via N-glycosylation of 20 with pyrimidine bases.
Scheme 33: Synthesis of 85 via N-glycosylation of 20 with purine bases.
Scheme 34: Synthesis of 86 and 87 via N-glycosylation using TMSOTf and pyrimidines.
Scheme 35: Synthesis of 90 and 91 via N-glycosylation using TMSOTf and purines.
Scheme 36: Synthesis of 3TC (1) via TMSI-mediated N-glycosylation.
Scheme 37: Stereoselective N-glycosylation for the synthesis of 1 by anchimeric assistance of a chiral auxilia...
Scheme 38: Whitehead and co-workers’ approach for the synthesis of 1 via direct N-glycosylation without an act...
Scheme 39: ZrCl4-mediated stereoselective N-glycosylation.
Scheme 40: Plausible reaction mechanism for stereoselective N-glycosylation using ZrCl4.
Scheme 41: Synthesis of enantiomerically pure oxathiolane nucleosides 1 and 2.
Scheme 42: Synthesis of tetrazole analogues of 1,3-oxathiolane nucleosides 97.
Scheme 43: Synthetic approach toward 99 from 1,3-oxathiolane 45 by Camplo et al.
Scheme 44: Synthesis of 100 from oxathiolane phosphonate analogue 46.
Scheme 45: Synthetic approach toward 102 and the corresponding cyclic thianucleoside monophosphate 102a by Cha...
Scheme 46: Synthesis of emtricitabine (2) from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g).
Scheme 47: Synthesis of 1 and 2, respectively, from 56a–d using iodine-mediated N-glycosylation.
Scheme 48: Plausible mechanism for silane- and I2-mediated N-glycosylation.
Scheme 49: Pyridinium triflate-mediated N-glycosylation of 35a.
Scheme 50: Possible pathway for stereoselective N-glycosylation via in situ chelation with a metal ligand.
Scheme 51: Synthesis of novel 1,3-oxathiolane nucleoside 108 from oxathiolane precursor 8 and 3-benzyloxy-2-me...
Scheme 52: Synthesis of 110 using T-705 as a nucleobase and 1,3-oxathiolane derivative 8 via N-glycosylation.
Scheme 53: Synthesis of 1 using an asymmetric leaving group and N-glycosylation with bromine and mesitylene.
Scheme 54: Cytidine deaminase for enzymatic separation of 1c.
Scheme 55: Enzymatic resolution of the monophosphate derivative 116 for the synthesis of (−)-BCH-189 (1) and (...
Scheme 56: Enantioselective resolution by PLE-mediated hydrolysis to obtain FTC (2).
Scheme 57: (+)-Menthyl chloroformate as a resolving agent to separate a racemic mixture 120.
Scheme 58: Separation of racemic mixture 1c by cocrystal 123 formation with (S)-(−)-BINOL.
α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions
- Scott Benz and
- Andrew S. Murkin
Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172
- enzymatic base (B), ring opens and subsequently rearranges to 74. AuaH uses NADH to reduce the ketone to diol 75, which undergoes dehydration to give aurachin B (76). The conversion of asperfloroid (73) to asperflotone (72), featuring the ring-expanding α-ketol rearrangement of 74 to form 75. Hypothetical
Graphical Abstract
Figure 1: Generalized α-ketol or α-iminol rearrangement.
Figure 2: Nickel(II)-catalyzed enantioselective rearrangement of ketol 3 to form the ring-expanded and chiral...
Figure 3: Enantioselective ring expansion of β-hydroxy-α-dicarbonyl 6 catalyzed by a chiral copper-bisoxazoli...
Figure 4: Enantioselective rearrangement of ketols 9 and 12 and hydroxyaldimine 14 catalyzed by Al(III) or Sc...
Figure 5: Asymmetric rearrangement of α,α-dialkyl-α-siloxyaldehydes 16 to α-siloxyketones 17 catalyzed by chi...
Figure 6: BF3-promoted diastereospecific rearrangement of α-ketol 21 to difluoroalkoxyborane 22.
Figure 7: In the presence of a gold catalyst and water in 1,4-dioxane, 1-alkynylbutanol derivatives undergo t...
Figure 8: The diastereospecific α-ketol rearrangement of 32 to 33, part of the total synthesis of periconiano...
Figure 9: Two α-ketol rearrangements, one catalyzed by silica gel on 38 and the other by NaOMe on both 38 and ...
Figure 10: α-Ketol rearrangement of triumphalone (41) to isotriumphalone (42) via ring contraction.
Figure 11: Tandem reaction of strophasterol A synthetic intermediate 43 to 44 through a vinylogous α-ketol rea...
Figure 12: Tandem reaction consisting of a Diels–Alder cycloaddition followed by an α-ketol rearrangement, par...
Figure 13: Single-pot reaction consisting of Claisen and α-ketol rearrangements, part of the total synthesis o...
Figure 14: Enzyme-catalyzed α-ketol rearrangements. a) Ketol-acid reductoisomerase (KAR) catalyzes the rearran...
Figure 15: The conversion of asperfloroid (73) to asperflotone (72), featuring the ring-expanding α-ketol rear...
Figure 16: Hypothetical interconversion of natural products prekinamycin (76) and isoprekinamycin (77) and che...
Figure 17: Proposed biosynthetic pathway converting acylphloroglucinol (87) to isolated elodeoidins A–H 92–96....
Figure 18: α-Iminol rearrangements catalyzed by VANOL Zr (99). The rearrangement can be conducted with preform...
Figure 19: α-Iminol rearrangements catalyzed by silica gel and montmorillonite K 10. a) For 102a (102 with R =...
Figure 20: Synthesis of tryptamines 110 via a ring-contracting α‑iminol rearrangement. A mechanism for the fin...
Figure 21: Tandem synthesis of functionalized α-amino cyclopentanones 119 from heteroarenes 115 and cyclobutan...
Figure 22: Four eburnane-type alkaloid natural products 122–125 were synthesized from common intermediate 127,...
Strategies for the synthesis of brevipolides
- Yudhi D. Kurniawan and
- A'liyatur Rosyidah
Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157
- reduced in a stereoselective manner adopting Luche conditions to provide diol 24 (dr 97:3), which after masking the primary alcohol moiety as a silyl ether, allowed isolation of the desired product 25 in 86% yield. This intermediate possessed the correct chirality on the free secondary alcohol to
- desired epoxide 30 after one hour in 85% yield (dr 10:1). This species was next converted to the terminal carbonate derivative 31 to transform the epoxy functionality to a vicinal diol through a two-step manipulation involving protection of the terminal alcohol as Boc derivative followed by BF3·Et2O
- acid (17) (Scheme 4). The β-hydroxy moiety in 44 can be installed via Sharpless dihydroxylation of the silyl enol ether derived from ketone 45. The 5,6-dihydro-α-pyrone group in ketone 45 is envisaged from protected diol 46 by the sequence of Mitsunobu esterification, ring-closing metathesis, and base
Graphical Abstract
Figure 1: Structures of brevipolides A–O (1 – 15).
Scheme 1: Retrosynthetic analysis of brevipolide H (8) by Kumaraswamy.
Scheme 2: Attempt to synthesize brevipolide H (8) by Kumaraswamy. (R,R)-Noyori cat. = RuCl[N-(tosyl)-1,2-diph...
Scheme 3: Attempt to synthesize brevipolide H (8) by Kumaraswamy (continued).
Scheme 4: Retrosynthetic analysis of brevipolide H (8) by Hou.
Scheme 5: Synthesis ent-brevipolide H (ent-8) by Hou.
Scheme 6: Retrosynthetic analysis of brevipolide H (8) by Mohapatra.
Scheme 7: Attempt to synthesize brevipolide H (8) by Mohapatra.
Scheme 8: Attempt to synthesize brevipolide H (8) by Mohapatra (continued). (+)-(IPC)2-BCl = (+)-B-chloro-dii...
Scheme 9: Retrosynthetic analysis of brevipolide H (8) by Hou.
Scheme 10: Synthesis of brevipolide H (8) by Hou.
Scheme 11: Retrosynthetic analysis of brevipolide M (13) by Sabitha.
Scheme 12: Synthesis of brevipolide M (13) by Sabitha.
Scheme 13: Retrosynthetic analysis of brevipolides M (13) and N (14) by Sabitha.
Scheme 14: Synthesis of brevipolides M (13) and N (14) by Sabitha.
Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds
- Sumana Mandal,
- Raju D. Chaudhari and
- Goutam Biswas
Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153
- ) [101]. Later it was shown that alkynyl diol 150 when treated with 20 mol % Hg(OTf)2 followed by Et3SiH afforded bispyranoyl ketone 151, but when Hg(OTf)2 was increased (1 equiv) then fused pyran-oxocane derivative 152 was isolated [102]. Six-membered morpholine derivatives were also synthesized by
- , hippuristanol and some analogs were successfully synthesized utilizing a Hg(OTf)2-catalyzed cascade spiroketalization step of the 3-alkyne-1,7-diol motif. The Hg(OTf)2-catalyzed cascade spiroketalization step was proved to be more convenient than Suárez cyclization. A Hg(TFA)2-mediated cyclization was
Graphical Abstract
Scheme 1: Schematic representation of Hg(II)-mediated addition to an unsaturated bond.
Scheme 2: First report of Hg(II)-mediated synthesis of 2,5-dioxane derivatives from allyl alcohol.
Scheme 3: Stepwise synthesis of 2,6-distubstituted dioxane derivatives.
Scheme 4: Cyclization of carbohydrate alkene precursor.
Scheme 5: Hg(II)-mediated synthesis of C-glucopyranosyl derivatives.
Scheme 6: Synthesis of C-glycosyl amino acid derivative using Hg(TFA)2.
Scheme 7: Hg(OAc)2-mediated synthesis of α-ᴅ-ribose derivative.
Scheme 8: Synthesis of β-ᴅ-arabinose derivative 18.
Scheme 9: Hg(OAc)2-mediated synthesis of tetrahydrofuran derivatives.
Scheme 10: Synthesis of Hg(TFA)2-mediated bicyclic nucleoside derivative.
Scheme 11: Synthesis of pyrrolidine and piperidine derivatives.
Scheme 12: HgCl2-mediated synthesis of diastereomeric pyrrolidine derivatives.
Scheme 13: HgCl2-mediated cyclization of alkenyl α-aminophosphonates.
Scheme 14: Cyclization of 4-cycloocten-1-ol with Hg(OAc)2 forming fused bicyclic products.
Scheme 15: trans-Amino alcohol formation through Hg(II)-salt-mediated cyclization.
Scheme 16: Hg(OAc)2-mediated 2-aza- or 2-oxa-bicyclic ring formations.
Scheme 17: Hg(II)-salt-induced cyclic peroxide formation.
Scheme 18: Hg(OAc)2-mediated formation of 1,2,4-trioxanes.
Scheme 19: Endocyclic enol ether derivative formation through Hg(II) salts.
Scheme 20: Synthesis of optically active cyclic alanine derivatives.
Scheme 21: Hg(II)-salt-mediated formation of tetrahydropyrimidin-4(1H)-one derivatives.
Scheme 22: Cyclization of ether derivatives to form stereoselective oxazolidine derivatives.
Scheme 23: Cyclization of amide derivatives induced by Hg(OAc)2.
Scheme 24: Hg(OAc)2/Hg(TFA)2-promoted cyclization of salicylamide-derived amidal auxiliary derivatives.
Scheme 25: Hg(II)-salt-mediated cyclization to form dihydrobenzopyrans.
Scheme 26: HgCl2-induced cyclization of acetylenic silyl enol ether derivatives.
Scheme 27: Synthesis of exocyclic and endocyclic enol ether derivatives.
Scheme 28: Cyclization of trans-acetylenic alcohol by treatment with HgCl2.
Scheme 29: Synthesis of benzofuran derivatives in presence of HgCl2.
Scheme 30: a) Hg(II)-salt-mediated cyclization of 4-hydroxy-2-alkyn-1-ones to furan derivatives and b) its mec...
Scheme 31: Cyclization of arylacetylenes to synthesize carbocyclic and heterocyclic derivatives.
Scheme 32: Hg(II)-salt-promoted cyclization–rearrangement to form heterocyclic compounds.
Scheme 33: a) HgCl2-mediated cyclization reaction of tethered alkyne dithioacetals; and b) proposed mechanism.
Scheme 34: Cyclization of aryl allenic ethers on treatment with Hg(OTf)2.
Scheme 35: Hg(TFA)2-mediated cyclization of allene.
Scheme 36: Hg(II)-catalyzed intramolecular trans-etherification reaction of 2-hydroxy-1-(γ-methoxyallyl)tetrah...
Scheme 37: a) Cyclization of alkene derivatives by catalytic Hg(OTf)2 salts and b) mechanism of cyclization.
Scheme 38: a) Synthesis of 1,4-dihydroquinoline derivatives by Hg(OTf)2 and b) plausible mechanism of formatio...
Scheme 39: Synthesis of Hg(II)-salt-catalyzed heteroaromatic derivatives.
Scheme 40: Hg(II)-salt-catalyzed synthesis of dihydropyranone derivatives.
Scheme 41: Hg(II)-salt-catalyzed cyclization of alkynoic acids.
Scheme 42: Hg(II)-salt-mediated cyclization of alkyne carboxylic acids and alcohol to furan, pyran, and spiroc...
Scheme 43: Hg(II)-salt-mediated cyclization of 1,4-dihydroxy-5-alkyne derivatives.
Scheme 44: Six-membered morpholine derivative formation by catalytic Hg(II)-salt-induced cyclization.
Scheme 45: Hg(OTf)2-catalyzed hydroxylative carbocyclization of 1,6-enyne.
Scheme 46: a) Hg(OTf)2-catalyzed hydroxylative carbocyclization of 1,6-enyne. b) Proposed mechanism.
Scheme 47: a) Synthesis of carbocyclic derivatives using a catalytic amount of Hg(II) salt. b) Proposed mechan...
Scheme 48: Cyclization of 1-alkyn-5-ones to 2-methylfuran derivatives.
Scheme 49: Hg(NO3)2-catalyzed synthesis of 2-methylenepiperidine.
Scheme 50: a) Preparation of indole derivatives through cycloisomerization of 2-ethynylaniline and b) its mech...
Scheme 51: a) Hg(OTf)2-catalyzed synthesis of 3-indolinones and 3-coumaranones and b) simplified mechanism.
Scheme 52: a) Hg(OTf)2-catalyzed one pot cyclization of nitroalkyne and b) its plausible mechanism.
Scheme 53: Synthesis of tricyclic heterocyclic scaffolds.
Scheme 54: HgCl2-mediated cyclization of 2-alkynylphenyl alkyl sulfoxide.
Scheme 55: a) Hg(OTf)2-catalyzed cyclization of allenes and alkynes. b) Proposed mechanism of cyclization.
Scheme 56: Stereoselective synthesis of tetrahydropyran derivatives.
Scheme 57: a) Hg(ClO4)2-catalyzed cyclization of α-allenol derivatives. b) Simplified mechanism.
Scheme 58: Hg(TFA)2-promoted cyclization of a γ-hydroxy alkene derivative.
Scheme 59: Synthesis Hg(II)-salt-mediated cyclization of allyl alcohol for the construction of ventiloquinone ...
Scheme 60: Hg(OAc)2-mediated cyclization as a key step for the synthesis of hongconin.
Scheme 61: Examples of Hg(II)-salt-mediated cyclized ring formation in the syntheses of (±)-fastigilin C and (...
Scheme 62: Formal synthesis of (±)-thallusin.
Scheme 63: Total synthesis of hippuristanol and its analog.
Scheme 64: Total synthesis of solanoeclepin A.
Scheme 65: a) Synthesis of Hg(OTf)2-catalyzed azaspiro structure for the formation of natural products. b) Pro...
Recent advances in the syntheses of anthracene derivatives
- Giovanni S. Baviera and
- Paulo M. Donate
Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131
- yields (89–94%) and mild reaction conditions [53]. In a related approach, in 2015, Mohanakrishnan and his group reported the synthesis of anthracene derivatives and other annulated products via the regioselective cyclization of asymmetric 1,2-diarylmethine diol 83b by using a HBr/AcOH system (Scheme 20
- converted to the substituted anthracenes 109 and 110 by varying the acidic workup procedures. In addition, they prepared 9-chloro-10-phenylanthracene (112) in good yield (87%) through diol 111 [59]. Synthesis of substituted benzo[a]anthracene and dibenzoanthracene derivatives Metal-catalyzed C–H bond
Graphical Abstract
Figure 1: Examples of anthracene derivatives and their applications.
Scheme 1: Rhodium-catalyzed oxidative coupling reactions of arylboronic acids with internal alkynes.
Scheme 2: Rhodium-catalyzed oxidative benzannulation reactions of 1-adamantoyl-1-naphthylamines with internal...
Scheme 3: Gold/bismuth-catalyzed cyclization of o-alkynyldiarylmethanes.
Scheme 4: [2 + 2 + 2] Cyclotrimerization reactions with alkynes/nitriles in the presence of nickel and cobalt...
Scheme 5: Cobalt-catalyzed [2 + 2 + 2] cyclotrimerization reactions with bis(trimethylsilyl)acetylene (23).
Scheme 6: [2 + 2 + 2] Alkyne-cyclotrimerization reactions catalyzed by a CoCl2·6H2O/Zn reagent.
Scheme 7: Pd(II)-catalyzed sp3 C–H alkenylation of diphenyl carboxylic acids with acrylates.
Scheme 8: Pd(II)-catalyzed sp3 C–H arylation with o-tolualdehydes and aryl iodides.
Scheme 9: Alkylation of arenes with aromatic aldehydes in the presence of acetyl bromide and ZnBr2/SiO2.
Scheme 10: BF3·H2O-catalyzed hydroxyalkylation of arenes with aromatic dialdehyde 44.
Scheme 11: Bi(OTf)3-promoted Friedel–Crafts alkylation of triarylmethanes and aromatic acylals and of arenes a...
Scheme 12: Reduction of anthraquinones by using Zn/pyridine or Zn/NaOH reductive methods.
Scheme 13: Two-step route to novel substituted Indenoanthracenes.
Scheme 14: Synthesis of 1,8-diarylanthracenes through Suzuki–Miyaura coupling reaction in the presence of Pd-P...
Scheme 15: Synthesis of five new substituted anthracenes by using LAH as reducing agent.
Scheme 16: One-pot procedure to synthesize substituted 9,10-dicyanoanthracenes.
Scheme 17: Reduction of bromoanthraquinones with NaBH4 in alkaline medium.
Scheme 18: In(III)-catalyzed reductive-dehydration intramolecular cycloaromatization of 2-benzylic aromatic al...
Scheme 19: Acid-catalyzed cyclization of new O-protected ortho-acetal diarylmethanols.
Scheme 20: Lewis acid-mediated regioselective cyclization of asymmetric diarylmethine dipivalates and diarylme...
Scheme 21: BF3·OEt2/CF3SO3H-mediated cyclodehydration reactions of 2-(arylmethyl)benzaldehydes and 2-(arylmeth...
Scheme 22: Synthesis of 2,3,6,7-anthracenetetracarbonitrile (90) by double Wittig reaction followed by deprote...
Scheme 23: Homo-elongation protocol for the synthesis of substituted acene diesters/dinitriles.
Scheme 24: Synthesis of two new parental BN anthracenes via borylative cyclization.
Scheme 25: Synthesis of substituted anthracenes from a bifunctional organomagnesium alkoxide.
Scheme 26: Palladium-catalyzed tandem C–H activation/bis-cyclization of propargylic carbonates.
Scheme 27: Ruthenium-catalyzed C–H arylation of acetophenone derivatives with arenediboronates.
Scheme 28: Pd-catalyzed intramolecular cyclization of (Z,Z)-p-styrylstilbene derivatives.
Scheme 29: AuCl-catalyzed double cyclization of diiodoethynylterphenyl compounds.
Scheme 30: Iodonium-induced electrophilic cyclization of terphenyl derivatives.
Scheme 31: Oxidative photocyclization of 1,3-distyrylbenzene derivatives.
Scheme 32: Oxidative cyclization of 2,3-diphenylnaphthalenes.
Scheme 33: Suzuki-Miyaura/isomerization/ring closing metathesis strategy to synthesize benz[a]anthracenes.
Scheme 34: Green synthesis of oxa-aza-benzo[a]anthracene and oxa-aza-phenanthrene derivatives.
Scheme 35: Triple benzannulation of substituted naphtalene via a 1,3,6-naphthotriyne synthetic equivalent.
Scheme 36: Zinc iodide-catalyzed Diels–Alder reactions with 1,3-dienes and aroyl propiolates followed by intra...
Scheme 37: H3PO4-promoted intramolecular cyclization of substituted benzoic acids.
Scheme 38: Palladium-catalyzed intermolecular direct acylation of aromatic aldehydes and o-iodoesters.
Scheme 39: Cycloaddition/oxidative aromatization of quinone and β-enamino esters.
Scheme 40: ʟ-Proline-catalyzed [4 + 2] cycloaddition reaction of naphthoquinones and α,β-unsaturated aldehydes....
Scheme 41: Iridium-catalyzed [2 + 2 + 2] cycloaddition of a 1,2-bis(propiolyl)benzene derivative with alkynes.
Scheme 42: Synthesis of several anthraquinone derivatives by using InCl3 and molecular iodine.
Scheme 43: Indium-catalyzed multicomponent reactions employing 2-hydroxy-1,4-naphthoquinone (186), β-naphthol (...
Scheme 44: Synthesis of substituted anthraquinones catalyzed by an AlCl3/MeSO3H system.
Scheme 45: Palladium(II)-catalyzed/visible light-mediated synthesis of anthraquinones.
Scheme 46: [4 + 2] Anionic annulation reaction for the synthesis of substituted anthraquinones.
Progress and challenges in the synthesis of sequence controlled polysaccharides
- Giulio Fittolani,
- Theodore Tyrikos-Ergas,
- Denisa Vargová,
- Manishkumar A. Chaube and
- Martina Delbianco
Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129
- resulting 2,3-diol as acceptor in the following glycosylation [131]. A regioselective glycosylation strategy was developed to obtain a collection of linear glucans (8mer to 16mer) (Scheme 4), as well as a branched 9mer and 17mer [137][138]. A similar strategy based on the regioselective glycosylation of a
- 2,3-diol 4,6-O-benzylidene acceptor permitted to access various β(1–3)-glucans, ranging from trimer to 13mer [126]. Regioselectivity was also achieved using a gold-catalyzed glycosylation, to give a linear β(1–3)-linked 11mer and a branched 14mer in a convergent manner [139]. Collection of linear as
Graphical Abstract
Figure 1: Overview of the methods available for the synthesis of polysaccharides. For each method, advantages...
Figure 2: Overview of the classes of polysaccharides discussed in this review. Each section deals with polysa...
Scheme 1: Enzymatic and chemical polymerization approaches provide cellulose oligomers with a non-uniform dis...
Scheme 2: AGA of a collection of cellulose analogues obtained using BBs 6–9. Specifically placed modification...
Figure 3: Chemical structure of the different branches G, X, L, F commonly found in XGs. Names are given foll...
Scheme 3: AGA of XG analogues with defined side chains. The AGA cycle includes coupling (TMSOTf), Fmoc deprot...
Figure 4: Synthetic strategies and issues associated to the formation of the β(1–3) linkage.
Scheme 4: Convergent synthesis of β(1–3)-glucans using a regioselective glycosylation strategy.
Scheme 5: DMF-mediated 1,2-cis glycosylation. A) General mechanism and B) examples of α-glucans prepared usin...
Scheme 6: Synergistic glycosylation strategy employing a nucleophilic modulation strategy (TMSI and Ph3PO) in...
Scheme 7: Different approaches to produce xylans. A) Polymerization techniques including ROP, and B) enzymati...
Scheme 8: A) Synthesis of arabinofuranosyl-decorated xylan oligosaccharides using AGA. Representative compoun...
Scheme 9: Chemoenzymatic synthesis of COS utilizing a lysozyme-catalyzed transglycosylation reaction followed...
Scheme 10: Synthesis of COS using an orthogonal glycosylation strategy based on the use of two different LGs.
Scheme 11: Orthogonal N-PGs permitted the synthesis of COS with different PA.
Scheme 12: AGA of well-defined COS with different PA using two orthogonally protected BBs. The AGA cycle inclu...
Scheme 13: A) AGA of β(1–6)-N-acetylglucosamine hexasaccharide and dodecasaccharide. AGA includes cycles of co...
Figure 5: ‘Double-faced’ chemistry exemplified for ᴅ-Man and ʟ-Rha. Constructing β-Man linkages is considerab...
Figure 6: Implementation of a capping step after each glycosylation cycle for the AGA of a 50mer oligomannosi...
Scheme 14: AGA enabled the synthesis of a linear α(1–6)-mannoside 100mer 93 within 188 h and with an average s...
Scheme 15: The 151mer branched polymannoside was synthesized by a [30 + 30 + 30 + 30 + 31] fragment coupling. ...
Figure 7: PG stereocontrol strategy to obtain β-mannosides. A) The mechanism of the β-mannosylation reaction ...
Scheme 16: A) Mechanism of 1,2-cis stereoselective glycosylation using ManA donors. Once the ManA donor is act...
Figure 8: A) The preferred 4H3 conformation of the gulosyl oxocarbenium ion favors the attack of the alcohol ...
Scheme 17: AGA of type I rhamnans up to 16mer using disaccharide BB 115 and CNPiv PG. The AGA cycle includes c...
Figure 9: Key BBs for the synthesis of the O-antigen of Bacteroides vulgatus up to a 128mer (A) and the CPS o...
Figure 10: Examples of type I and type II galactans synthesized to date.
Figure 11: A) The DTBS PG stabilizes the 3H4 conformation of the Gal oxocarbenium ion favoring the attack of t...
Figure 12: Homogalacturonan oligosaccharides synthesized to date. Access to different patterns of methyl-ester...
Figure 13: GlfT2 from Mycobacterium tuberculosis catalyzes the sequential addition of UPD-Galf donor to a grow...
Figure 14: The poor reactivity of acceptor 137 hindered a stepwise synthesis of the linear galactan backbone a...
Scheme 18: AGA of a linear β(1–5) and β(1–6)-linked galactan 20mer. The AGA cycle includes coupling (NIS/TfOH)...
Figure 15: The 92mer arabinogalactan was synthesized using a [31 + 31 + 30] fragment coupling between a 31mer ...
Scheme 19: Synthesis of the branched arabinofuranose fragment using a six component one-pot synthesis. i) TTBP...
Figure 16: A) Chemical structure and SNFG of the representative disaccharide units forming the GAG backbones, ...
Figure 17: Synthetic challenges associated to the H/HS synthesis.
Scheme 20: Degradation of natural heparin and heparosan generated valuable disaccharides 150 and 151 that can ...
Scheme 21: A) The one-step conversion of cyanohydrin 156 to ʟ-iduronamide 157 represent the key step for the s...
Scheme 22: A) Chemoenzymatic synthesis of heparin structures, using different types of UDP activated natural a...
Scheme 23: Synthesis of the longest synthetic CS chain 181 (24mer) using donor 179 and acceptor 180 in an iter...
Scheme 24: AGA of a collection of HA with different lengths. The AGA cycle includes coupling (TfOH) and Lev de...
On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets
- Renato L. Carvalho,
- Amanda S. de Miranda,
- Mateus P. Nunes,
- Roberto S. Gomes,
- Guilherme A. M. Jardim and
- Eufrânio N. da Silva Júnior
Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126
- [158]. The synthesis started with a cyclopentene derivative, obtained after two steps from a diol via tosylation/displacement strategy with Me2CuLi·LiI. Then, after a Lewis acid-promoted cycloaddition, the alkylation of the α-carbon atom followed by regioselective Baeyer–Villiger oxidation provided the
Graphical Abstract
Scheme 1: Schematic overview of transition metals studied in C–H activation processes.
Scheme 2: (A) Known biological activities related to benzimidazole-based compounds; (B and C) an example of a...
Scheme 3: (A) Known biological activities related to quinoline-based compounds; (B and C) an example of a sca...
Scheme 4: (A) Known biological activities related to sulfur-containing compounds; (B and C) an example of a s...
Scheme 5: (A) Known biological activities related to aminoindane derivatives; (B and C) an example of a scand...
Scheme 6: (A) Known biological activities related to norbornane derivatives; (B and C) an example of a scandi...
Scheme 7: (A) Known biological activities related to aniline derivatives; (B and C) an example of a titanium-...
Scheme 8: (A) Known biological activities related to cyclohexylamine derivatives; (B) an example of an intram...
Scheme 9: (A) Known biologically active benzophenone derivatives; (B and C) photocatalytic oxidation of benzy...
Scheme 10: (A) Known bioactive fluorine-containing compounds; (B and C) vanadium-mediated C(sp3)–H fluorinatio...
Scheme 11: (A) Known biologically active Lythraceae alkaloids; (B) synthesis of (±)-decinine (30).
Scheme 12: (A) Synthesis of (R)- and (S)-boehmeriasin (31); (B) synthesis of phenanthroindolizidines by vanadi...
Scheme 13: (A) Known bioactive BINOL derivatives; (B and C) vanadium-mediated oxidative coupling of 2-naphthol...
Scheme 14: (A) Known antiplasmodial imidazopyridazines; (B) practical synthesis of 41.
Scheme 15: (A) Gold-catalyzed drug-release mechanism using 2-alkynylbenzamides; (B and C) chromium-mediated al...
Scheme 16: (A) Examples of anti-inflammatory benzaldehyde derivatives; (B and C) chromium-mediated difunctiona...
Scheme 17: (A and B) Manganese-catalyzed chemoselective intramolecular C(sp3)–H amination; (C) late-stage modi...
Scheme 18: (A and B) Manganese-catalyzed C(sp3)–H amination; (C) late-stage modification of a leelamine deriva...
Scheme 19: (A) Known bioactive compounds containing substituted N-heterocycles; (B and C) manganese-catalyzed ...
Scheme 20: (A) Known indoles that present GPR40 full agonist activity; (B and C) manganese-catalyzed C–H alkyl...
Scheme 21: (A) Examples of known biaryl-containing drugs; (B and C) manganese-catalyzed C–H arylation through ...
Scheme 22: (A) Known zidovudine derivatives with potent anti-HIV properties; (B and C) manganese-catalyzed C–H...
Scheme 23: (A and B) Manganese-catalyzed C–H organic photo-electrosynthesis; (C) late-stage modification.
Scheme 24: (A) Example of a known antibacterial silylated dendrimer; (B and C) manganese-catalyzed C–H silylat...
Scheme 25: (A and B) Fe-based small molecule catalyst applied for selective aliphatic C–H oxidations; (C) late...
Scheme 26: (A) Examples of naturally occurring gracilioethers; (B) the first total synthesis of gracilioether ...
Scheme 27: (A and B) Selective aliphatic C–H oxidation of amino acids; (C) late-stage modification of proline-...
Scheme 28: (A) Examples of Illicium sesquiterpenes; (B) first chemical synthesis of (+)-pseudoanisatin (80) in...
Scheme 29: (A and B) Fe-catalyzed deuteration; (C) late-stage modification of pharmaceuticals.
Scheme 30: (A and B) Biomimetic Fe-catalyzed aerobic oxidation of methylarenes to benzaldehydes (PMHS, polymet...
Scheme 31: (A) Known tetrahydroquinolines with potential biological activities; (B and C) redox-selective Fe c...
Scheme 32: (A) Known drugs containing a benzofuran unit; (B and C) Fe/Cu-catalyzed tandem O-arylation to acces...
Scheme 33: (A) Known azaindolines that act as M4 muscarinic acetylcholine receptor agonists; (B and C) intramo...
Scheme 34: (A) Known indolinones with anticholinesterase activity; (B and C) oxidative C(sp3)–H cross coupling...
Scheme 35: (A and B) Cobalt-catalyzed C–H alkenylation of C-3-peptide-containing indoles; (C) derivatization b...
Scheme 36: (A) Cobalt-Cp*-catalyzed C–H methylation of known drugs; (B and C) scope of the o-methylated deriva...
Scheme 37: (A) Known lasalocid A analogues; (B and C) three-component cobalt-catalyzed C–H bond addition; (D) ...
Scheme 38: (A and B) Cobalt-catalyzed C(sp2)–H amidation of thiostrepton.
Scheme 39: (A) Known 4H-benzo[d][1,3]oxazin-4-one derivatives with hypolipidemic activity; (B and C) cobalt-ca...
Scheme 40: (A and B) Cobalt-catalyzed C–H arylation of pyrrole derivatives; (C) application for the synthesis ...
Scheme 41: (A) Known 2-phenoxypyridine derivatives with potent herbicidal activity; (B and C) cobalt-catalyzed...
Scheme 42: (A) Natural cinnamic acid derivatives; (B and C) cobalt-catalyzed C–H carboxylation of terminal alk...
Scheme 43: (A and B) Cobalt-catalyzed C–H borylation; (C) application to the synthesis of flurbiprofen.
Scheme 44: (A) Benzothiazoles known to present anticonvulsant activities; (B and C) cobalt/ruthenium-catalyzed...
Scheme 45: (A and B) Cobalt-catalyzed oxygenation of methylene groups towards ketone synthesis; (C) synthesis ...
Scheme 46: (A) Known anticancer tetralone derivatives; (B and C) cobalt-catalyzed C–H difluoroalkylation of ar...
Scheme 47: (A and B) Cobalt-catalyzed C–H thiolation; (C) application in the synthesis of quetiapine (153).
Scheme 48: (A) Known benzoxazole derivatives with anticancer, antifungal, and antibacterial activities; (B and...
Scheme 49: (A and B) Cobalt-catalyzed C–H carbonylation of naphthylamides; (C) BET inhibitors 158 and 159 tota...
Scheme 50: (A) Known bioactive pyrrolo[1,2-a]quinoxalin-4(5H)-one derivatives; (B and C) cobalt-catalyzed C–H ...
Scheme 51: (A) Known antibacterial cyclic sulfonamides; (B and C) cobalt-catalyzed C–H amination of propargyli...
Scheme 52: (A and B) Cobalt-catalyzed intramolecular 1,5-C(sp3)–H amination; (C) late-stage functionalization ...
Scheme 53: (A and B) Cobalt-catalyzed C–H/C–H cross-coupling between benzamides and oximes; (C) late-state syn...
Scheme 54: (A) Known anticancer natural isoquinoline derivatives; (B and C) cobalt-catalyzed C(sp2)–H annulati...
Scheme 55: (A) Enantioselective intramolecular nickel-catalyzed C–H activation; (B) bioactive obtained motifs;...
Scheme 56: (A and B) Nickel-catalyzed α-C(sp3)–H arylation of ketones; (C) application of the method using kno...
Scheme 57: (A and B) Nickel-catalyzed C(sp3)–H acylation of pyrrolidine derivatives; (C) exploring the use of ...
Scheme 58: (A) Nickel-catalyzed C(sp3)–H arylation of dioxolane; (B) library of products obtained from biologi...
Scheme 59: (A) Intramolecular enantioselective nickel-catalyzed C–H cycloalkylation; (B) product examples, inc...
Scheme 60: (A and B) Nickel-catalyzed C–H deoxy-arylation of azole derivatives; (C) late-stage functionalizati...
Scheme 61: (A and B) Nickel-catalyzed decarbonylative C–H arylation of azole derivatives; (C) application of t...
Scheme 62: (A and B) Another important example of nickel-catalyzed C–H arylation of azole derivatives; (C) app...
Scheme 63: (A and B) Another notable example of a nickel-catalyzed C–H arylation of azole derivatives; (C) lat...
Scheme 64: (A and B) Nickel-based metalorganic framework (MOF-74-Ni)-catalyzed C–H arylation of azole derivati...
Scheme 65: (A) Known commercially available benzothiophene-based drugs; (B and C) nickel-catalyzed C–H arylati...
Scheme 66: (A) Known natural tetrahydrofuran-containing substances; (B and C) nickel-catalyzed photoredox C(sp3...
Scheme 67: (A and B) Another notable example of a nickel-catalyzed photoredox C(sp3)–H alkylation/arylation; (...
Scheme 68: (A) Electrochemical/nickel-catalyzed C–H alkoxylation; (B) achieved scope, including three using na...
Scheme 69: (A) Enantioselective photoredox/nickel catalyzed C(sp3)–H arylation; (B) achieved scope, including ...
Scheme 70: (A) Known commercially available trifluoromethylated drugs; (B and C) nickel-catalyzed C–H trifluor...
Scheme 71: (A and B) Stereoselective nickel-catalyzed C–H difluoroalkylation; (C) late-stage functionalization...
Scheme 72: (A) Cu-mediated ortho-amination of oxalamides; (B) achieved scope, including derivatives obtained f...
Scheme 73: (A) Electro-oxidative copper-mediated amination of 8-aminoquinoline-derived amides; (B) achieved sc...
Scheme 74: (A and B) Cu(I)-mediated C–H amination with oximes; (C) derivatization using telmisartan (241) as s...
Scheme 75: (A and B) Cu-mediated amination of aryl amides using ammonia; (C) late-stage modification of proben...
Scheme 76: (A and B) Synthesis of purine nucleoside analogues using copper-mediated C(sp2)–H activation.
Scheme 77: (A) Copper-mediated annulation of acrylamide; (B) achieved scope, including the synthesis of the co...
Scheme 78: (A) Known bioactive compounds containing a naphthyl aryl ether motif; (B and C) copper-mediated eth...
Scheme 79: (A and B) Cu-mediated alkylation of N-oxide-heteroarenes; (C) late-stage modification.
Scheme 80: (A) Cu-mediated cross-dehydrogenative coupling of polyfluoroarenes and alkanes; (B) scope from know...
Scheme 81: (A) Known anticancer acrylonitrile compounds; (B and C) Copper-mediated cyanation of unactivated al...
Scheme 82: (A) Cu-mediated radiofluorination of 8-aminoquinoline-derived aryl amides; (B) achieved scope, incl...
Scheme 83: (A) Examples of natural β-carbolines; (B and C) an example of a zinc-catalyzed C–H functionalizatio...
Scheme 84: (A) Examples of anticancer α-aminophosphonic acid derivatives; (B and C) an example of a zinc-catal...
Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus
- Jana M. Boysen,
- Nauman Saeed and
- Falk Hillmann
Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124
- more likely to survive internalization by lung epithelial cells [147][154][155]. Although DHN-melanin is generally associated with immune evasion it was recently found to be recognized in higher animals via the C-type lectin receptor (MelLec) which interacts with the naphthalene-diol domain of DHN
Graphical Abstract
Figure 1: Schematic overview of fungal interactions in the environment. Fungi can be found in essentially all...
Figure 2: Fungal derived bioactive natural compounds with ecological and/or economic relevance.
Figure 3: Gliotoxin biosynthetic gene cluster and it major biosynthetic transformations: Gliotoxin (5) is the...
Figure 4: Amoebicidal secondary metabolites trypacidin and fumagillin of Aspergillus fumigatus.
Figure 5: Intermediates of the DHN-melanin biosynthesis in Aspergillus fumigatus.
Figure 6: Intermediates and products of the fumigaclavine C biosynthesis.
Figure 7: Bioactive secondary metabolites of Aspergillus fumigatus.
Figure 8: Helvolic acid gene cluster of A. fumigatus.
Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols
- Jie Zheng,
- Shuyu Meng and
- Quanrui Wang
Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104
- alkynyl-Prins cyclization, Friedel–Crafts alkenylation, and dehydration/aromatization reaction between 1-aryl-3-hexyne-2,6-diol derivatives and aldehydes, that led to the formation of 1,4-dihydro-2H-benzo[f]isochromenes [16]. The Prins reaction-induced cyclization, inter alia, became a versatile tool for
Graphical Abstract
Figure 1: Parent structure of 2,4-disubstituted tetralins (1) and selected medicinally useful derivatives 2–4....
Scheme 1: Reported strategies for the synthesis of tetralin-2-ol ring systems.
Scheme 2: Designed cascade reactions to 4-substituted tetralin-2-ols.
Scheme 3: The documented synthesis of 2-(2-vinylphenyl)acetaldehyde (13a).
Scheme 4: Modified synthesis of 2-(2-vinylphenyl)acetaldehydes 13a–g and 1-vinyl-2-naphthaldehyde (13h).
Scheme 5: Lewis acid-catalyzed Prins/Friedel–Crafts reaction of 13a with veratrole.
Figure 2: The speculated stereostructures of compound cis-14aa and trans-14aa.
Scheme 6: Use of different nucleophiles for the cascade reaction with 13a. Reaction conditions: a mixture of ...
Scheme 7: Reaction of aldehydes 13b–h with veratrole or furan. Reaction conditions: a mixture of 13b–h (1.40 ...
Scheme 8: Synthesis of 5-aryltetrahydro-5H-benzo[7]annulen-7-ols 20a, b.
Scheme 9: Conversion of 2-hydroxy-4-(2-furyl)tetralin (14af) into PAT analogue 22.
Figure 3: Crystal structure of the tosylate 21. The displacement ellipsoids are drawn at the 30% probability ...
Total synthesis of ent-pavettamine
- Memory Zimuwandeyi,
- Manuel A. Fernandes,
- Amanda L. Rousseau and
- Moira L. Bode
Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99
- 1995, was previously identified as a polyamine with C2 symmetry and a 1,3-syn-diol moiety on a C10 carbon backbone – one of very few substituted polyamines to be isolated from nature. Its absolute configuration was later established by our first reported total synthesis in 2010. Herein we report the
- -pavettamine rather than pavettamine. Chain extension and stereoselective ketone reduction were achieved using the (R)-methyl p-tolyl sulfoxide chiral auxiliary to give the desired 1,3-syn-diol C5 unit. A protecting-group strategy was also developed for the orthogonal protection of the alcohol and amine
- yield. The first step involved esterification of malic acid using methanol, followed by selective reduction of the resulting dimethyl ester using borane dimethyl sulfide (BMS) yielding diol 5 (Scheme 2) [1][14][15]. The step achieved chemo-differentiation of the carboxyl groups present in 3 whilst
Graphical Abstract
Figure 1: Structure of pavettamine 1 and its enantiomer 2.
Scheme 1: Established route for the synthesis of intermediate 4 [1].
Scheme 2: Alternative route. Reaction conditions: a) TrCl, pyridine, rt, overnight, 100%; b) DMAP, imidazole,...
Figure 2: Crystal structure of compound 9.
Scheme 3: Sequence showing the source of compound 9.
Scheme 4: Stereoselective reduction of intermediate 8 as key step towards intermediate 4. Reaction conditions...
Figure 3: Single crystal X-ray structure of compound 4.
Scheme 5: Synthesis of the C5 fragments from intermediate 4. Reaction conditions: a) i) TFAA, collidine, 0 °C...
Scheme 6: Synthesis of ent-pavettamine as the TFA salt 28. Reaction conditions: a) IBX, DMSO, rt, overnight, ...
Double-headed nucleosides: Synthesis and applications
- Vineet Verma,
- Jyotirmoy Maity,
- Vipin K. Maikhuri,
- Ritika Sharma,
- Himal K. Ganguly and
- Ashok K. Prasad
Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98
- -headed nucleosides 151a–d starting from LNA uridine diol 147 which in turn was synthesized from diacetone-α-ᴅ-allose following a procedure reported in the literature [76]. LNA uridine diol 147 was reacted with iodine and ceric ammonium nitrate (CAN) in acetic acid to afford the nucleoside 148. Nucleoside
Graphical Abstract
Figure 1: Double-headed nucleosides. B1 and B2 = nucleobases or heterocyclic/carbocyclic moieties; L = linker....
Scheme 1: Synthesis of 2′-(pyrimidin-1-yl)methyl- or 2′-(purin-9-yl)methyl-substituted double-headed nucleosi...
Scheme 2: Synthesis of double-headed nucleoside 7 having two cytosine moieties.
Scheme 3: Synthesis of double-headed nucleoside 2′-deoxy-2′-C-(2-(thymine-1-yl)ethyl)-uridine (11).
Scheme 4: Double-headed nucleosides 14 and 15 obtained by click reaction.
Scheme 5: Synthesis of the double-headed nucleoside 19.
Scheme 6: Synthesis of the double-headed nucleosides 24 and 25.
Scheme 7: Synthesis of double-headed nucleosides 28 and 29.
Scheme 8: Synthesis of double-headed nucleoside 33.
Scheme 9: Synthesis of double-headed nucleoside 37.
Scheme 10: Synthesis of the double-headed nucleoside 1-(5′-O-(4,4′-dimethoxytrityl)-2′-C-((4-(pyren-1-yl)-1,2,...
Scheme 11: Synthesis of triazole-containing double-headed ribonucleosides 46a–c and 50a–e.
Scheme 12: Synthesis of double-headed nucleosides 54a–g.
Scheme 13: Synthesis of double-headed nucleosides 59 and 60.
Scheme 14: Synthesis of the double-headed nucleosides 63 and 64.
Scheme 15: Synthesis of double-headed nucleosides 66a–c.
Scheme 16: Synthesis of benzoxazole-containing double-headed nucleosides 69 and 71 from 5′-amino-5′-deoxynucle...
Scheme 17: Synthesis of 4′-C-((N6-benzoyladenin-9-yl)methyl)thymidine (75) and 4′-C-((thymin-1-yl)methyl)thymi...
Scheme 18: Synthesis of double-headed nucleosides 5′-(adenine-9-yl)-5′-deoxythymidine (79) and 5′-(adenine-9-y...
Scheme 19: Synthesis of double-headed nucleosides 85–87 via reversed nucleosides methodology.
Scheme 20: Double-headed nucleosides 91 and 92 derived from ω-terminal-acetylenic sugar derivatives 90a,b.
Scheme 21: Synthesis of double-headed nucleosides 96a–g.
Scheme 22: Synthesis of double-headed nucleosides 100 and 103.
Scheme 23: Double-headed nucleosides 104 and 105 with a triazole motif.
Scheme 24: Synthesis of the double-headed nucleosides 107 and 108.
Scheme 25: Synthesis of double-headed nucleoside 110 with additional nucleobase in 5′-(S)-C-position joined th...
Scheme 26: Synthesis of double-headed nucleosides 111–113 with additional nucleobases in the 5′-(S)-C-position...
Scheme 27: Synthesis of double-headed nucleoside 114 by click reaction.
Scheme 28: Synthesis of double-headed nucleosides 118 with an additional nucleobase at the 5′-(S)-C-position.
Scheme 29: Synthesis of bicyclic double-headed nucleoside 122.
Scheme 30: Synthesis of double-headed nucleosides 125a–c derived from 2′-amino-LNA.
Scheme 31: Double-headed nucleoside 127 obtained by click reaction.
Scheme 32: Synthesis of double-headed nucleoside 130.
Scheme 33: Double-headed nucleosides 132a–d and 134a–d synthesized by Sonogashira cross coupling reaction.
Scheme 34: Synthesis of double-headed nucleosides 137 and 138 via Suzuki coupling.
Scheme 35: Synthesis of double-headed nucleosides 140 and 141 via Sonogashira cross coupling reaction.
Scheme 36: Synthesis of double-headed nucleoside 143.
Scheme 37: Synthesis of the double-headed nucleoside 146.
Scheme 38: Synthesis of 5-C-alkynyl-functionalized double-headed nucleosides 151a–d.
Scheme 39: Synthesis of 5-C-triazolyl-functionalized double-headed nucleosides 154a, b.
Scheme 40: Synthesis of double-headed nucleosides 157a–c.
Scheme 41: Synthesis of double-headed nucleoside 159, phosphoramidite 160 and the corresponding nucleotide mon...
Scheme 42: Synthesis of double-headed nucleoside 163, phosphoramidite 164 and the corresponding nucleotide mon...
Scheme 43: Synthesis of double-headed nucleoside 167, phosphoramidite 168, and the corresponding nucleotide mo...
Scheme 44: Synthesis of double-headed nucleoside 171, phosphoramidite 172, and the corresponding nucleotide mo...
Scheme 45: Synthesis of double-headed nucleoside 175, phosphoramidite 176, and the corresponding nucleotide mo...
Scheme 46: Synthesis of double-headed nucleoside 178.
Scheme 47: Synthesis of the double-headed nucleosides 181 and 183.
Scheme 48: Alternative synthesis of the double-headed nucleoside 183.
Scheme 49: Synthesis of double-headed nucleoside 188 through thermal [2 + 3] sydnone–alkyne cycloaddition reac...
Scheme 50: Synthesis of the double-headed nucleosides 190 and 191.
Scheme 51: Synthesis of 1-((5S)-2,3,4-tri-O-acetyl-5-(2,6-dichloropurin-9-yl)-β-ᴅ-xylopyranosyl)uracil (195).
Scheme 52: Synthesis of hexopyranosyl double-headed pyrimidine homonucleosides 200a–c.
Figure 2: 3′-C-Ethynyl-β-ᴅ-allopyranonucleoside derivatives 201a–f.
Scheme 53: Synthesis of 3′-C-(1,4-disubstituted-1,2,3-triazolyl)-double-headed pyranonucleosides 203–207.
Scheme 54: Synthesis of 3′-C-(1,4-disubstituted-1,2,3-triazolyl)-double-headed pyranonucleosides 208 and 209.
Scheme 55: Synthesis of 3′-C-(1,4-disubstituted-1,2,3-triazolyl)-double-headed pyranonucleoside 210.
Scheme 56: Synthesis of double-headed acyclic nucleosides (2S,3R)-1,4-bis(thymine-1-yl)butane-2,3-diol (213a) ...
Scheme 57: Synthesis of double-headed acyclic nucleosides (2R,3S)-1,4-bis(thymine-1-yl)butane-2,3-diol (213c) ...
Scheme 58: Synthesis of double-headed acetylated 1,3,4-oxadiazino[6,5-b]indolium-substituted C-nucleosides 218b...
Scheme 59: Synthesis of double-headed acyclic nucleoside 222.
Scheme 60: Synthesis of functionalized 1,2-bis(1,2,4-triazol-3-yl)ethane-1,2-diols 223a–f.
Scheme 61: Synthesis of acyclic double-headed 1,2,4-triazino[5,6-b]indole C-nucleosides 226–231.
Scheme 62: Synthesis of double-headed 1,3,4-thiadiazoline, 1,3,4-oxadiazoline, and 1,2,4-triazoline acyclo C-n...
Scheme 63: Synthesis of double-headed acyclo C-nucleosides 240–242.
Scheme 64: Synthesis of double-headed acyclo C-nucleoside 246.
Scheme 65: Synthesis of acyclo double-headed nucleoside 250.
Scheme 66: Synthesis of acyclo double-headed nucleoside 253.
Scheme 67: Synthesis of acyclo double-headed nucleosides 259a–d.
Scheme 68: Synthesis of acyclo double-headed nucleoside 261.
N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles
- Joseane A. Mendes,
- Paulo R. R. Costa,
- Miguel Yus,
- Francisco Foubelo and
- Camilla D. Buarque
Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86
- trimethylsilyl cyanide (TMSCN) in THF at −10 °C. The reaction product 142 was obtained in quantitative yield and good diastereomeric ratio. Further hydrolysis of the cyclic acetal, and subsequent epoxidation of the resulting diol under typical Mitsunobu conditions led to epoxide derivative 143. The piperidine
Graphical Abstract
Scheme 1: General strategy for the enantioselective synthesis of N-containing heterocycles from N-tert-butane...
Scheme 2: Methodologies for condensation of aldehydes and ketones with tert-butanesulfinamides (1).
Scheme 3: Transition models for cis-aziridines and trans-aziridines.
Scheme 4: Mechanism for the reduction of N-tert-butanesulfinyl imines.
Scheme 5: Transition models for the addition of organomagnesium and organolithium compounds to N-tert-butanes...
Scheme 6: Synthesis of 2,2-dibromoaziridines 15 from aldimines 14 and bromoform, and proposed non-chelation-c...
Scheme 7: Diastereoselective synthesis of aziridines from tert-butanesulfinyl imines.
Scheme 8: Synthesis of vinylaziridines 22 from aldimines 14 and 1,3-dibromopropene 23, and proposed chelation...
Scheme 9: Synthesis of vinylaziridines 27 from aldimines 14 and α-bromoesters 26, and proposed transition sta...
Scheme 10: Synthesis of 2-chloroaziridines 28 from aldimines 14 and dichloromethane, and proposed transition s...
Scheme 11: Synthesis of cis-vinylaziridines 30 and 31 from aldimines 14 and bromomethylbutenolide 29.
Scheme 12: Synthesis of 2-chloro-2-aroylaziridines 36 and 32 from aldimines 14, arylnitriles 34, and silyldich...
Scheme 13: Synthesis of trifluoromethylaziridines 39 and proposed transition state of the aziridination.
Scheme 14: Synthesis of aziridines 42 and proposed state transition.
Scheme 15: Synthesis of 1-substituted 2-azaspiro[3.3]heptanes, 1-phenyl-2-azaspiro[3.4]octane and 1-phenyl-2-a...
Scheme 16: Synthesis of 1-substituted 2,6-diazaspiro[3.3]heptanes 48 from chiral imines 14 and 1-Boc-azetidine...
Scheme 17: Synthesis of β-lactams 52 from chiral imines 14 and dimethyl malonate (49).
Scheme 18: Synthesis of spiro-β-lactam 57 from chiral (RS)-N-tert-butanesulfinyl isatin ketimine 53 and ethyl ...
Scheme 19: Synthesis of β-lactam 60, a precursor of (−)-batzelladine D (61) and (−)-13-epi-batzelladine D (62)...
Scheme 20: Rhodium-catalyzed asymmetric synthesis of 3-substituted pyrrolidines 66 from chiral imine (RS)-63 a...
Scheme 21: Asymmetric synthesis of 1,3-disubstituted isoindolines 69 and 70 from chiral imine 67.
Scheme 22: Asymmetric synthesis of cis-2,5-disubstituted pyrrolidines 73 from chiral imine (RS)-71.
Scheme 23: Asymmetric synthesis of 3-hydroxy-5-substituted pyrrolidin-2-ones 77 from chiral imine (RS)-74.
Scheme 24: Asymmetric synthesis of 4-hydroxy-5-substituted pyrrolidin-2-ones 80 from chiral imines 79.
Scheme 25: Asymmetric synthesis of 3-pyrrolines 82 from chiral imines 14 and ethyl 4-bromocrotonate (81).
Scheme 26: Asymmetric synthesis of γ-amino esters 84, and tetramic acid derivative 86 from chiral imines (RS)-...
Scheme 27: Asymmetric synthesis of α-methylene-γ-butyrolactams 90 from chiral imines (Z,SS)-87 and ethyl 2-bro...
Scheme 28: Asymmetric synthesis of methylenepyrrolidines 92 from chiral imines (RS)-14 and 2-(trimethysilylmet...
Scheme 29: Synthesis of dibenzoazaspirodecanes from cyclic N-tert-butanesulfinyl imines.
Scheme 30: Stereoselective synthesis of cyclopenta[c]proline derivatives 103 from β,γ-unsaturated α-amino acid...
Scheme 31: Stereoselective synthesis of alkaloids (−)-angustureine (107) and (−)-cuspareine (108).
Scheme 32: Stereoselective synthesis of alkaloids (−)-pelletierine (112) and (+)-coniine (117).
Scheme 33: Synthesis of piperidine alkaloids (+)-dihydropinidine (122a), (+)-isosolenopsin (122b) and (+)-isos...
Scheme 34: Stereoselective synthesis of the alkaloids(+)-sedamine (125) from chiral imine (SS)-119.
Scheme 35: Stereoselective synthesis of trans-5-hydroxy-6-substituted-2-piperidinones 127 and 129 from chiral ...
Scheme 36: Stereoselective synthesis of trans-5-hydroxy-6-substituted ethanone-2-piperidinones 132 from chiral...
Scheme 37: Stereoselective synthesis of trans-3-benzyl-5-hydroxy-6-substituted-2-piperidinones 136 from chiral...
Scheme 38: Stereoselective synthesis of trans-5-hydroxy-6-substituted 2-piperidinones 139 from chiral imine 138...
Scheme 39: Stereoselective synthesis of ʟ-hydroxypipecolic acid 145 from chiral imine 144.
Scheme 40: Synthesis of 1-substituted isoquinolones 147, 149 and 151.
Scheme 41: Stereoselective synthesis of 3-substituted dihydrobenzo[de]isoquinolinones 154.
Scheme 42: Enantioselective synthesis of alkaloids (S)-1-benzyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (...
Scheme 43: Enantioselective synthesis of alkaloids (−)-cermizine B (171) and (+)-serratezomine E (172) develop...
Scheme 44: Stereoselective synthesis of (+)-isosolepnosin (177) and (+)-solepnosin (178) from homoallylamine d...
Scheme 45: Stereoselective synthesis of tetrahydroquinoline derivatives 184, 185 and 187 from chiral imines (RS...
Scheme 46: Stereoselective synthesis of pyridobenzofuran and pyridoindole derivatives 193 from homopropargylam...
Scheme 47: Stereoselective synthesis of 2-substituted 1,2,5,6-tetrahydropyridines 196 from chiral imines (RS)-...
Scheme 48: Stereoselective synthesis of 2-substituted trans-2,6-disubstituted piperidine 199 from chiral imine...
Scheme 49: Stereoselective synthesis of cis-2,6-disubstituted piperidines 200, and alkaloid (+)-241D, from chi...
Scheme 50: Stereoselective synthesis of 6-substituted piperidines-2,5-diones 206 and 1,7-diazaspiro[4.5]decane...
Scheme 51: Stereoselective synthesis of spirocyclic oxindoles 210 from chiral imines (RS)-53.
Scheme 52: Stereoselective synthesis of azaspiro compound 213 from chiral imine 211.
Scheme 53: Stereoselective synthesis of tetrahydroisoquinoline derivatives from chiral imines (RS)-214.
Scheme 54: Stereoselective synthesis of (−)-crispine A 223 from chiral imine (RS)-214.
Scheme 55: Synthesis of (−)-harmicine (228) using tert-butanesulfinamide through haloamide cyclization.
Scheme 56: Stereoselective synthesis of tetraponerines T1–T8.
Scheme 57: Stereoselective synthesis of phenanthroindolizidines 246a and (−)-tylophorine (246b), and phenanthr...
Scheme 58: Stereoselective synthesis of indoline, tetrahydroquinoline and tetrahydrobenzazepine derivatives 253...
Scheme 59: Stereoselective synthesis of (+)-epohelmin A (258) and (+)-epohelmin B (260) from aldimine (RS)-79.
Scheme 60: Stereoselective synthesis of (−)-epiquinamide (266) from chiral aldimine (SS)-261.
Scheme 61: Synthesis synthesis of (–)-hippodamine (273) and (+)-epi-hippodamine (272) using chiral sulfinyl am...
Scheme 62: Stereoselective synthesis of (+)-grandisine D (279) and (+)-amabiline (283).
Scheme 63: Stereoselective synthesis of (−)-epiquinamide (266) and (+)-swaisonine (291) from aldimine (SS)-126....
Scheme 64: Stereoselective synthesis of (+)-C(9a)-epi-epiquinamide (294).
Scheme 65: Stereoselective synthesis of (+)-lasubine II (298) from chiral aldimine (SS)-109.
Scheme 66: Stereoselective synthesis of (−)-epimyrtine (300a) and (−)-lasubine II (ent-302) from β-amino keton...
Scheme 67: Stereoselective synthesis of (−)-tabersonine (310), (−)-vincadifformine (311), and (−)-aspidospermi...
Scheme 68: Stereoselective synthesis of (+)-epohelmin A (258) and (+)-epohelmin B (260) from aldehyde 313 and ...
Scheme 69: Total synthesis of (+)-lysergic acid (323) from N-tert-butanesulfinamide (RS)-1.
Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides
- Vojtěch Hamala,
- Lucie Červenková Šťastná,
- Martin Kurfiřt,
- Petra Cuřínová,
- Martin Dračínský and
- Jindřich Karban
Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85
- thioglycosides 27–31 (Scheme 3). As the 3,4-difluorinated thiogalactoside could not be accessed from compound 13 by reaction with PhSTMS/ZnI2 (Scheme 2), it was necessary to obtain 3,4-difluoro and 3,4,6-trifluoro analogs of GalNAc from 3-fluoro-4,6-diol 18. According to precedents in the literature [53
- ], deoxyfluorination of the C4-hydroxy group in compound 18 was expected to occur with inversion of configuration to give the desired galacto-configured 4-fluoro products. Accordingly, treatment of diol 18 with DAST resulted in deoxyfluorination of both hydroxy groups to yield trifluoro thiogalactosazide 34 (Scheme 3
- ). 4,6-O-Benzylidenation of diol 18 followed by regioselective opening of the benzylidene acetal produced compound 35. Subsequent DAST deoxyfluorination delivered the desired thioglycoside 36 (Scheme 3). For both compounds 18 and 35, deoxyfluorination of the C4 hydroxy group occurred with inversion of
Graphical Abstract
Scheme 1: Retrosynthetic analysis of the target fluoro analogs.
Scheme 2: Conversion of 1,6-anhydro derivatives into thioglycosides, and a possible mechanism for the formati...
Scheme 3: Deoxyfluorination and O-benzylation of thioglycosides and thioaglycone migration.
Scheme 4: Thioglycoside hydrolysis.
Scheme 5: Synthesis of the target compounds by azide/acetamide conversion and debenzylation.
Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols
- Ákos Bajtel,
- Mounir Raji,
- Matti Haukka,
- Ferenc Fülöp and
- Zsolt Szakonyi
Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80
- -amino-1,3-diols, which underwent a regioselective ring closure with formaldehyde or benzaldehyde delivering pinane-condensed oxazolidines. During the preparation of 2-phenyliminooxazolidine, an interesting ring–ring tautomerism was observed in CDCl3. Keywords: 2-amino-1,2-diol; monoterpene; oxazolidin
- -2-one; stereoselective; tautomerism; Introduction The best known 2-amino-1,3-diol derivative sphingosine (1) plays a crucial role in intracellular signaling as second messenger, and its derivatives called sphingolipids are also critical for cell growth, cell differentiation, cell recognition, and
- the lack of a readily available natural sources and the high biological importance of sphingolipid analogues, their synthesis has been the subject of numerous studies [16]. The key step for the synthesis is the stereoselective construction of the 2-amino-1,3-diol moiety of the molecules. Generally
Graphical Abstract
Figure 1: Biologically active 2-amino-1,3-diols.
Scheme 1: Stereoselective synthesis of the pinane-fused oxazolidin-2-one 9.
Figure 2: NOESY experiments and X-ray structure elucidation of oxazolidin-2-one 9.
Scheme 2: Stereoselective synthesis of the pinane spiro-fused oxazolidin-2-one 12.
Scheme 3: Parallel synthesis of 2-amino-1,3-diols.
Scheme 4: Synthesis of N-benzyl-2-amino-1,3-diol 16.
Scheme 5: Synthesis of 2-amino-1,3-diols.
Figure 3: NOESY experiments and X-ray structure proofment of the structure of oxazolidine 17.
Scheme 6: Synthesis of 2-phenyliminooxazolidines.
Figure 4: Proposed pathway for the ring–ring tautomerism.
Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years
- Asha Budakoti,
- Pradip Kumar Mondal,
- Prachi Verma and
- Jagadish Khamrai
Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77
- the synthesis of diol by the condensation of styrene and paraformaldehyde in the presence of a Brønsted acid [23][24]. The major breakthrough for this reaction was reported by Hanschke in 1955, when the THP ring was selectively constructed through a Prins reaction involving 3-butene-1-ol and a variety
Graphical Abstract
Scheme 1: General strategy for the synthesis of THPs.
Scheme 2: Developments towards the Prins cyclization.
Scheme 3: General stereochemical outcome of the Prins cyclization.
Scheme 4: Regioselectivity in the Prins cyclization.
Scheme 5: Mechanism of the oxonia-Cope reaction in the Prins cyclization.
Scheme 6: Cyclization of electron-deficient enantioenriched alcohol 27.
Scheme 7: Partial racemization through 2-oxonia-Cope allyl transfer.
Scheme 8: Partial racemization by reversible 2-oxonia-Cope rearrangement.
Scheme 9: Rychnovsky modification of the Prins cyclization.
Scheme 10: Synthesis of (−)-centrolobine and the C22–C26 unit of phorboxazole A.
Scheme 11: Axially selective Prins cyclization by Rychnovsky et al.
Scheme 12: Mechanism for the axially selectivity Prins cyclization.
Scheme 13: Mukaiyama aldol–Prins cyclization reaction.
Scheme 14: Application of the aldol–Prins reaction.
Scheme 15: Hart and Bennet's acid-promoted Prins cyclization.
Scheme 16: Tetrahydropyran core of polycarvernoside A as well as (−)-clavoslide A and D.
Scheme 17: Scheidt and co-workers’ route to tetrahydropyran-4-one.
Scheme 18: Mechanism for the Lewis acid-catalyzed synthesis of tetrahydropyran-4-one.
Scheme 19: Hoveyda and co-workers’ strategy for 2,6-disubstituted 4-methylenetetrahydropyran.
Scheme 20: Funk and Cossey’s ene-carbamates strategy.
Scheme 21: Yadav and Kumar’s cyclopropane strategy for THP synthesis.
Scheme 22: 2-Arylcylopropylmethanolin in centrolobine synthesis.
Scheme 23: Yadav and co-workers’ strategy for the synthesis of THP.
Scheme 24: Yadav and co-workers’ Prins–Ritter reaction sequence for 4-amidotetrahydropyran.
Scheme 25: Yadav and co-workers’ strategy to prelactones B, C, and V.
Scheme 26: Yadav and co-workers’ strategy for the synthesis of (±)-centrolobine.
Scheme 27: Loh and co-workers’ strategy for the synthesis of zampanolide and dactylolide.
Scheme 28: Loh and Chan’s strategy for THP synthesis.
Scheme 29: Prins cyclization of cyclohexanecarboxaldehyde.
Scheme 30: Prins cyclization of methyl ricinoleate (127) and benzaldehyde (88).
Scheme 31: AlCl3-catalyzed cyclization of homoallylic alcohol 129 and aldehyde 130.
Scheme 32: Martín and co-workers’ stereoselective approach for the synthesis of highly substituted tetrahydrop...
Scheme 33: Ene-IMSC strategy by Marko and Leroy for the synthesis of tetrahydropyran.
Scheme 34: Marko and Leroy’s strategy for the synthesis of tetrahydropyrans 146.
Scheme 35: Sakurai dimerization/macrolactonization reaction for the synthesis of cyanolide A.
Scheme 36: Hoye and Hu’s synthesis of (−)-dactyloide by intramolecular Sakurai cyclization.
Scheme 37: Minehan and co-workers’ strategy for the synthesis of THPs 157.
Scheme 38: Yu and co-workers’ allylic transfer strategy for the construction of tetrahydropyran 161.
Scheme 39: Reactivity enhancement in intramolecular Prins cyclization.
Scheme 40: Floreancig and co-workers’ Prins cyclization strategy to (+)-dactyloide.
Scheme 41: Panek and Huang’s DHP synthesis from crotylsilanes: a general strategy.
Scheme 42: Panek and Huang’s DHP synthesis from syn-crotylsilanes.
Scheme 43: Panek and Huang’s DHP synthesis from anti-crotylsilanes.
Scheme 44: Roush and co-workers’ [4 + 2]-annulation strategy for DHP synthesis [82].
Scheme 45: TMSOTf-promoted annulation reaction.
Scheme 46: Dobb and co-workers’ synthesis of DHP.
Scheme 47: BiBr3-promoted tandem silyl-Prins reaction by Hinkle et al.
Scheme 48: Substrate scope of Hinkle and co-workers’ strategy.
Scheme 49: Cho and co-workers’ strategy for 2,6 disubstituted 3,4-dimethylene-THP.
Scheme 50: Furman and co-workers’ THP synthesis from propargylsilane.
Scheme 51: THP synthesis from silyl enol ethers.
Scheme 52: Rychnovsky and co-workers’ strategy for THP synthesis from hydroxy-substituted silyl enol ethers.
Scheme 53: Li and co-workers’ germinal bissilyl Prins cyclization strategy to (−)-exiguolide.
Scheme 54: Xu and co-workers’ hydroiodination strategy for THP.
Scheme 55: Wang and co-workers’ strategy for tetrahydropyran synthesis.
Scheme 56: FeCl3-catalyzed synthesis of DHP from alkynylsilane alcohol.
Scheme 57: Martín, Padrón, and co-workers’ proposed mechanism of alkynylsilane Prins cyclization for the synth...
Scheme 58: Marko and co-workers’ synthesis of 2,6-anti-configured tetrahydropyran.
Scheme 59: Loh and co-workers’ strategy for 2,6-syn-tetrahydropyrans.
Scheme 60: Loh and co-workers’ strategy for anti-THP synthesis.
Scheme 61: Cha and co-workers’ strategy for trans-2,6-tetrahydropyran.
Scheme 62: Mechanism proposed by Cha et al.
Scheme 63: TiCl4-mediated cyclization to trans-THP.
Scheme 64: Feng and co-workers’ FeCl3-catalyzed Prins cyclization strategy to 4-hydroxy-substituted THP.
Scheme 65: Selectivity profile of the Prins cyclization under participation of an iron ligand.
Scheme 66: Sequential reactions involving Prins cyclization.
Scheme 67: Banerjee and co-workers’ strategy of Prins cyclization from cyclopropane carbaldehydes and propargy...
Scheme 68: Mullen and Gagné's (R)-[(tolBINAP)Pt(NC6F5)2][SbF6]2-catalyzed asymmetric Prins cyclization strateg...
Scheme 69: Yu and co-workers’ DDQ-catalyzed asymmetric Prins cyclization strategy to trisubstituted THPs.
Scheme 70: Lalli and Weghe’s chiral-Brønsted-acid- and achiral-Lewis-acid-promoted asymmetric Prins cyclizatio...
Scheme 71: List and co-workers’ iIDP Brønsted acid-promoted asymmetric Prins cyclization strategy.
Scheme 72: Zhou and co-workers’ strategy for chiral phosphoric acid (CPA)-catalyzed cascade Prins cyclization.
Scheme 73: List and co-workers’ approach for asymmetric Prins cyclization using chiral imidodiphosphoric acid ...
Kinetics of enzyme-catalysed desymmetrisation of prochiral substrates: product enantiomeric excess is not always constant
- Peter J. Halling
Beilstein J. Org. Chem. 2021, 17, 873–884, doi:10.3762/bjoc.17.73
- -pong second (ketone amination, diol esterification, desymmetrisation in the second half reaction); ping-pong first (diol ester hydrolysis) and ping-pong both (prochiral diacids). For plausible values of enzyme kinetic parameters, the product enantiomeric excess (ee) can decline substantially as the
- prochiral diols. The enzyme reacts with an amino or acyl donor, releasing a first co-product, to give an aminated or acylated enzyme intermediate. This then reacts with the prochiral ketone or diol to generate the chiral products. “Ping-pong, first”. Followed in most lipase or esterase hydrolyses of
- prochiral diol esters. The enzyme reacts enantiospecifically with the ester to release a chiral product, leaving the acyl group attached to the active site. In a second stage the achiral acyl group undergoes hydrolysis by water. In the desymmetrisation of diols (and diacids, below) kinetic amplification can
Graphical Abstract
Scheme 1: Kinetic mechanisms. In each case E represents the free enzyme, other species starting E are other e...
Figure 1: Reaction progress for “ordered, second” kinetics and the effect of D/Q (e.g., NADH/NAD+) ratio. S0 ...
Figure 2: Effect of the initial starting material concentration and enzyme E value for “ordered, second” kine...
Figure 3: Effects of key enzyme parameters on the fall in product ee during reaction for “ordered, second” ki...
Figure 4: Reaction progress for “ping-pong, second” kinetics, and the effect of the ratio of donor to prochir...
Figure 5: Effect of the key ee decline parameter (eeDP) of the enzyme on the product ee for “ping-pong, secon...
Figure 6: Effects of prochiral substrate concentration and its KM value for “ping-pong, first” kinetics. Inpu...
Figure 7: Effect of eeDP and k−4 · Keq/k4 on the product ee at high conversion for “ping-pong, first” kinetic...
Figure 8: Progress curves for “ping-pong, both” kinetics, diacid esterification. The plot shows the increasin...
Figure 9: Effects on the ee of the product formed early in the reaction for “ping-pong, both” kinetics, diaci...
Figure 10: Increase in the product ee as the reaction proceeds for “ping-pong, both” kinetics, diacid esterifi...
Figure 11: Effects on the ee at high conversion for diacid ester synthesis, “ping-pong, both” kinetics. Parame...
A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent
- Ke Wu,
- Yichen Ling,
- An Ding,
- Liqun Jin,
- Nan Sun,
- Baoxiang Hu,
- Zhenlu Shen and
- Xinquan Hu
Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69
- reckoned that converting compound A to a more polar derivative could probably be a breakthrough. As common knowledge, the more polarized alcohols over EtOH are those diols or polyols, while MeOH was previously ruled out. Ethylene glycol, a basic chemical and the simplest diol, is slightly soluble in
Graphical Abstract
Figure 1: Generation of the six-membered byproduct A from thionation reactions using Lawesson’s reagent.
Figure 2: Work-up procedure for the reaction with LR.
Figure 3: Modified process for the synthesis of 2e via phase separation.
Scheme 1: Modified process for the synthesis of pincer ligand 4.
Scheme 2: Modified process for the synthesis of pincer-type ligand 6.
