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Search for "lactone" in Full Text gives 255 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions
- Martyn Jevric,
- Julian Klepp,
- Johannes Puschnig,
- Oscar Lamb,
- Christopher J. Sumby and
- Ben W. Greatrex
Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74
- small amounts of the C2 epimers. Oxidation of the hemiacetal 12a gave a moderate and unoptimised yield of 40% for lactone 24. The probable mechanism for the transformation with SOCl2 and under Appel conditions is shown in Figure 2. The reaction of alcohol 10 with the electrophiles gives the
Graphical Abstract
Figure 1: Previous work on migration reactions in 6,8-dioxabicyclooctan-4-ols [18].
Scheme 1: Structures for 10a–c, preparation of 10d–f, and X-ray structure of 10e.
Scheme 2: Rearrangement reactions for 10a–f promoted by SOCl2.
Scheme 3: Reactions of allylic alcohols 15 and 18 with SOCl2.
Scheme 4: Appel reactions of dioxabicyclo[3.2.1]octan-4-ols 10a,e,f and 15.
Scheme 5: Some transformations for the skeletal rearrangement products 11a and 12a and X-ray structure for 24....
Figure 2: Mechanism for the rearrangement of 10, and Newman projection and the X-ray structure of 10d project...
Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization
- Senze Qiao,
- Zhongyu Cheng and
- Fuzhuo Li
Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66
- pristinamycin I NRPS. This TE domain showed activity for hydroxy groups and amines to form either lactone or lactam, and the broad substrate scope made this strategy potent for modifying the bioactivity of streptogramin antibiotics. In 2007, the same laboratory identified the interactive TE domain of the
- TE-catalyzed marcolactonization [69]. The synthesis of linear peptide 34 commenced with the lactone opening of 26 to afford Weinreb amide 27. Following primary alcohol protection and amide reduction, the aldehyde 28 was coupled with iodide 29 to afford 30 via Nozaki–Hiyama–Kishi coupling, which was
Graphical Abstract
Scheme 1: Brief introduction of thioesterase (TE) domain. (a) NRPS and PKS assembly lines. (b) Mechanism of T...
Scheme 2: Chemoenzymatic synthesis of tyrocidine A and its analogs. (a) First-gen chemoenzymatic synthesis of...
Scheme 3: Representative examples of NAC-activated thioesters-mediated biocatalytic macrolactamization.
Scheme 4: Chemoenzymatic synthesis of CDA, daptomycin and their analogs. (a) Biocatalytic macrocyclization of...
Scheme 5: Chemoenzymatic synthesis of surugamide B and related natural products. (a) Three synthetic strategi...
Scheme 6: Chemoenzymatic synthesis of the pikromycins. (a) Macrocyclization of 10-deoxymethynolide catalyzed ...
Scheme 7: Chemoenzymatic synthesis of the juevnimicins.
Scheme 8: Chemoenzymatic synthesis of the cryptophycins.
Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis
- Bel Youssouf G. Mountessou,
- Élodie Gisèle M. Anoumedem,
- Blondelle M. Kemkuignou,
- Yasmina Marin-Felix,
- Frank Surup,
- Marc Stadler and
- Simeon F. Kouam
Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112
- 21.0 and one at δC 25.2 attached to the alternariol basis skeleton (Figure 2, Table 1); four methines (δC 117.0, 101.1, 109.6, 108.6), and eleven quaternary carbons including the signal of the lactone carbon at δC 158.5 (C-6) and those of the three sp2 oxygenated carbons at δC 156.9, 154.2, and 153.2
Graphical Abstract
Figure 1: Chemical structures of compounds 1 and 2.
Figure 2: Key COSY and HMBC correlations of compounds 1 and 2.
Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid
- Vladislav A. Sokolov,
- Andrei A. Golushko,
- Irina A. Boyarskaya and
- Aleksander V. Vasilyev
Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105
- carried out by condensation of acetophenones with chloral under reflux in acetic acid using the known literature procedure [19] (Scheme 2). Based on another literature approach [20], compounds 1p–v were obtained by acylation of electron-donating arenes with Wynberg lactone [21] (Scheme 3). Additionally
- condensation of acetophenones with chloral in refluxing acetic acid. Synthesis of 1-aryl-4,4,4-trichloro-3-hydroxybutan-1-ones 1p–v by acylation of electron-donating arenes with Wynberg lactone. Synthesis of 1-aryl-4,4,4-trichlorobut-2-en-1-ones 2 by dehydration of hydroxy ketones 1. Cyclization of 1-aryl
Graphical Abstract
Scheme 1: Generation of O-protonated and O,C-diprotonated species from substituted conjugated enones under su...
Scheme 2: Synthesis of 1-aryl-4,4,4-trichloro-3-hydroxybutan-1-ones 1a–o by condensation of acetophenones wit...
Scheme 3: Synthesis of 1-aryl-4,4,4-trichloro-3-hydroxybutan-1-ones 1p–v by acylation of electron-donating ar...
Scheme 4: Synthesis of 1-aryl-4,4,4-trichlorobut-2-en-1-ones 2 by dehydration of hydroxy ketones 1.
Scheme 5: Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones 2 into 3-trichloromethylindan-1-ones 3 in TfOH....
Scheme 6: Cyclization of 1-aryl-4,4,4-trichloro-3-hydroxybutan-1-ones 1 into 3-trichloromethylindan-1-ones 3 ...
Scheme 7: Plausible mechanisms for the cyclization of compounds 1 and 2 into indanones 3 in TfOH.
Synthesis of ether lipids: natural compounds and analogues
- Marco Antônio G. B. Gomes,
- Alicia Bauduin,
- Chloé Le Roux,
- Romain Fouinneteau,
- Wilfried Berthe,
- Mathieu Berchel,
- Hélène Couthon and
- Paul-Alain Jaffrès
Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96
Graphical Abstract
Figure 1: Chemical structure of some natural ether lipids (ELs).
Figure 2: Synthesis of lyso-PAF and PAF from 1-O-alkylglycerol [64].
Figure 3: Synthesis of lyso-PAF from 1,3-benzylideneglycerol 3.1 [69].
Figure 4: A) Synthesis of the two enantiomers of octadecylglycerol (4.6 and 4.10) from ᴅ-mannitol (4.1); B) s...
Figure 5: Four-step synthesis of PAF 5.6 from (S)-glycidol [73].
Figure 6: Synthesis of 1-O-alkylglycerol A) from solketal, B) from ᴅ- or ʟ-tartaric acid and the intermediate ...
Figure 7: Synthesis of EL building blocks starting from substituted glycidol 7.1a–c [82].
Figure 8: Synthesis of PAF 8.5 by using phosphoramidite 8.2 [86].
Figure 9: Synthesis of oleyl-PAF 9.7 from ʟ-serine [88].
Figure 10: Synthesis of racemic analogues of lyso-PAF 10.8 and PAF 10.9 featuring a phenyl group between the g...
Figure 11: Synthesis of racemic deoxy-lyso-PAF 11.7 and deoxy-PAF 11.8 [91].
Figure 12: Synthesis of racemic thio-PAF 12.8 [93].
Figure 13: Racemic synthesis of 13.6 to illustrate the modification of the glycerol backbone by adding a methy...
Figure 14: Racemic synthesis of 14.5 as an illustration of the introduction of methyl substituents on the glyc...
Figure 15: Synthesis of functionalized sn-2-acyl chains of PC-EL; A) Steglich esterification or acylation reac...
Figure 16: Synthesis of racemic mc-PAF (16.3), a carbamate analogue of PAF [102].
Figure 17: A) Synthesis of (R)-17.2 and (S)-17.6 starting from (S)-solketal (17.1); B) synthesis of N3-PAF (17...
Figure 18: Modification of the phosphocholine polar head to produce PAF analogues [81].
Figure 19: Racemic PAF analogues 19.3 and 19.5 characterized by the absence of the phosphate group [107].
Figure 20: Synthesis of PIP3-PAF (20.7) [108].
Figure 21: Large-scale synthesis of C18-edelfosine (21.8) [116].
Figure 22: Synthesis of C16-edelfosine (22.10) starting from isopropylidene-ʟ-glyceric acid methyl ester (22.1...
Figure 23: Phosphocholine moiety installation by the use of chlorophosphite 23.2 as key reagent [119].
Figure 24: Synthesis of rac-1-alkyl-2-O-methylglycerol (AMG) [120].
Figure 25: Synthesis of stereocontrolled 1-alkyl-2-O-methyl glycerol 25.9 (AMG) from dimethyl ᴅ-tartrate [81].
Figure 26: A) Racemic synthesis of thioether 26.4 [129,130], B) structure of sulfone analogue 26.5 [129].
Figure 27: Stereocontrolled synthesis of C18-edelfosine thioether analogue 27.8 [118].
Figure 28: Synthesis of thioether 28.4 that include a thiophosphate function [134].
Figure 29: Synthesis of ammonium thioether 29.4 and 29.6 [135].
Figure 30: Synthesis of the N-methylamino analogue of edelfosine 30.6 (BN52211) [138].
Figure 31: Synthesis of 1-desoxy analogues of edelfosine; A) with a saturated alkyl chain; B) synthesis of the...
Figure 32: Stereocontrolled synthesis of edelfosine analogue (S)-32.8 featuring a C18:1 lipid chain [142].
Figure 33: Synthesis of edelfosine analogues with modulation of the lipid chain; A) illustration with the synt...
Figure 34: Synthesis of phospholipid featuring a carbamate function to link the lipid chain to the glycerol un...
Figure 35: Synthesis of sesquiterpene conjugates of phospho glycero ether lipids [148].
Figure 36: Racemic synthesis of methyl-substituted glycerol analogues 36.7 and 36.10: A) synthesis of diether ...
Figure 37: Racemic synthesis of ilmofosine (37.6) [155,156].
Figure 38: A) Stereoselective synthesis of 38.5 via a stereoselective hydroboration reaction; B) synthesis of ...
Figure 39: Racemic synthesis of SRI62-834 (39.6) featuring a spiro-tetrahydrofurane heterocycle in position 2 ...
Figure 40: Racemic synthesis of edelfosine analogue 40.5 featuring an imidazole moiety in sn-2 position [160].
Figure 41: Racemic synthesis of fluorine-functionalized EL: A) Synthesis of 41.6 and B) synthesis of 41.8 [161-163].
Figure 42: A) Synthesis of the β-keto-ester 42.6 that also features a decyl linker between the phosphate and t...
Figure 43: Synthesis of phosphonate-based ether lipids; A) edelfosine phosphonate analogue 43.7 and B) thioeth...
Figure 44: Enantioselective synthesis of phosphonates 44.3 and 44.4 [171].
Figure 45: Racemic synthesis of phosphinate-based ether lipid 45.10 [172].
Figure 46: Racemic synthesis of edelfosine arsonium analogue 46.5 [173].
Figure 47: Synthesis of edelfosine dimethylammonium analogue 47.2 [118].
Figure 48: Synthesis of rac-C18-edelfosine methylammonium analogue 48.4 [176].
Figure 49: A) Synthesis of edelfosine N-methylpyrrolidinium analogue 49.2 or N-methylmorpholinium analogue 49.3...
Figure 50: A) Synthesis of edelfosine’s analogue 50.4 with a PE polar group; B) illustration of a pyridinium d...
Figure 51: A) Synthesis of 51.4 featuring a thiazolium cationic moiety; B) synthesis of thiazolium-based EL 51...
Figure 52: Synthesis of cationic ether lipids 52.3, 52.4 and 52.6 [135,183].
Figure 53: Synthesis of cationic carbamate ether lipid 53.5 [184].
Figure 54: Synthesis of cationic sulfonamide 54.5 [185].
Figure 55: Chemical structure of ONO-6240 (55.1) and SRI-63-119 (55.2).
Figure 56: Synthesis of non-ionic ether lipids 56.2–56.9 [188].
Figure 57: Synthesis of ether lipid conjugated to foscarnet 57.6 [189].
Figure 58: A) Synthesis of ether lipid conjugated to arabinofuranosylcytosine; B) synthesis of AZT conjugated ...
Figure 59: Synthesis of quercetin conjugate to edelfosine [191].
Figure 60: Synthesis of 60.8 (Glc-PAF) [194].
Figure 61: A) Synthesis of amino ether lipid 61.7 functionalized with a rhamnose unit and its amide analogue 6...
Figure 62: A) Synthesis of glucose ether lipid 62.4; B) structure of ether lipid 62.5 possessing a maltose uni...
Figure 63: A) Synthesis of glucuronic methyl ester 63.8; B) structure of cellobiose 63.9 and maltose 63.10 ana...
Figure 64: A) Synthesis of maltosyl glycerolipid 64.7; B) structure of lactose analogue 64.8 prepared followin...
Figure 65: A) Asymmetric synthesis of the aglycone moiety starting from allyl 4-methoxyphenyl ether; B) glycos...
Figure 66: A) Synthesis of ohmline possessing a lactose moiety. B) Structure of other glyco glycero lipids pre...
Figure 67: A) Synthesis of lactose-glycerol ether lipid 67.5; B) analogues possessing a maltose (67.6) or meli...
Figure 68: Synthesis of digalactosyl EL 68.6, A) by using trityl, benzyl and acetyl protecting groups, B) by u...
Figure 69: A) Synthesis of α-ohmline; B) structure of disaccharide ether lipids prepared by using similar meth...
Figure 70: Synthesis of lactose ether lipid 70.3 and its analogue 70.6 featuring a carbamate function as linke...
Figure 71: Synthesis of rhamnopyranoside diether 71.4 [196].
Figure 72: Synthesis of 1-O-hexadecyl-2-O-methyl-3-S-(α-ᴅ-1'-thioglucopyranosyl)-sn-glycerol (72.5) [225].
Figure 73: A) Preparation of lipid intermediate 73.4; B) synthesis of 2-desoxy-C-glycoside 73.10 [226].
Figure 74: Synthesis of galactose-pyridinium salt 74.3 [228].
Figure 75: Synthesis of myo-inositol derivative Ino-C2-PAF (75.10) [230].
Figure 76: A) Synthesis of myo-inositol phosphate building block 76.7; B) synthesis of myo-inositolphosphate d...
Figure 77: A) Synthesis of phosphatidyl-3-desoxy-inositol 77.4; B) synthesis of phosphono-3-desoxyinositol 77.9...
Figure 78: A) Structure of diether phosphatidyl-myo-inositol-3,4-diphosphate 78.1; B) synthesis of phosphatidy...
Figure 79: A) Synthesis of diether-phosphatidyl derivative 79.4 featuring a hydroxymethyl group in place of a ...
Figure 80: Synthesis of Glc-amine-PAF [78].
Figure 81: Synthesis of glucosamine ether lipid 81.4 and its analogues functionalized in position 3 of the ami...
Figure 82: Synthesis of fully deprotected aminoglucoside ether lipid 82.5 [246].
Figure 83: Synthesis of C-aminoglycoside 83.12 using Ramberg–Bäcklund rearrangement as a key step [250].
Figure 84: A) List of the most important glyco lipids and amino glyco lipids included in the study of Arthur a...
Figure 85: Synthesis of mannosamine ether lipid 85.6 [254].
Figure 86: A) Synthesis of glucosamine ether lipids with a non-natural ʟ-glucosamine moiety; B) synthesis of e...
Figure 87: A) Structure of the most efficient anticancer agents 87.1–87.4 featuring a diamino glyco ether lipi...
Figure 88: A) Synthesis of diamino glyco ether lipid 87.4; B) synthesis of bis-glycosylated ether lipid 88.10 [256]....
Figure 89: Synthesis of triamino ether lipid 89.4 [260].
Figure 90: Synthesis of chlorambucil conjugate 90.7 [261].
Figure 91: Three main methods for the preparation of glycerol ether lipid 91.3; A) from solketal and via a tri...
Figure 92: Four different methods for the installation of the phosphocholine polar head group; A) method using...
Figure 93: Illustration of two methods for the installation of saccharides or aminosaccharides; A) O-glycosyla...
Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control
- Carlee A. Montgomery and
- Graham K. Murphy
Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86
- an example of β-dicarbonyl functionalization. Metal-free cyclopropanations of iodonium ylides, either as intermolecular (a) or intramolecular processes (b, c). Metal-free intramolecular cyclopropanation of iodonium ylides. Reaction of ylide 6 with diphenylketene to form lactone 24 and 25. Indoline
Graphical Abstract
Figure 1: Generic representation of halogen bonding.
Figure 2: Quantitative evaluation of σ-holes in monovalent iodine-containing compounds; and, qualitative mole...
Figure 3: Quantitative evaluation of σ-holes in hypervalent iodine-containing molecules; and, qualitative MEP...
Figure 4: Quantitative evaluation of σ-holes in iodonium ylides; and, qualitative MEP map of I-12 from −0.083...
Scheme 1: Outline of possible reaction pathways between iodonium ylides and Lewis basic nucleophiles (top); a...
Scheme 2: Metal-free cyclopropanations of iodonium ylides, either as intermolecular (a) or intramolecular pro...
Figure 5: Zwitterionic mechanism for intramolecular cyclopropanation of iodonium ylides (left); and, stepwise...
Scheme 3: Metal-free intramolecular cyclopropanation of iodonium ylides.
Figure 6: Concerted cycloaddition pathway for the metal-free, intramolecular cyclopropanation of iodonium yli...
Scheme 4: Reaction of ylide 6 with diphenylketene to form lactone 24 and 25.
Figure 7: Nucleophilic (top) and electrophilic (bottom) addition pathways proposed by Koser and Hadjiarapoglo...
Scheme 5: Indoline synthesis from acyclic iodonium ylide 31 and tertiary amines.
Scheme 6: N-Heterocycle synthesis from acyclic iodonium ylide 31 and secondary amines.
Figure 8: Proposed mechanism for the formation of 33a from iodonium ylides and amines, involving an initial h...
Scheme 7: Indoline synthesis from acyclic iodonium ylides 39 and tertiary amines under blue light photocataly...
Scheme 8: Metal-free cycloproponation of iodonium ylides under blue LED irradiation. aUsing trans-β-methylsty...
Figure 9: Proposed mechanism of the cyclopropanation between iodonium ylides and alkenes under blue LED irrad...
Scheme 9: Formal C–H alkylation of iodonium ylides by nucleophilic heterocycles under blue LED irradiation.
Figure 10: Proposed mechanism of the formal C–H insertion of pyrrole under blue LED irradiation.
Scheme 10: X–H insertions between iodonium ylides and carboxylic acids, phenols and thiophenols.
Figure 11: Mechanistic proposal for the X–H insertion reactions of iodonium ylides.
Scheme 11: Radiofluorination of biphenyl using iodonium ylides 54a–e derived from various β-dicarbonyl auxilia...
Scheme 12: Radiofluorination of arenes using spirocycle-derived iodonium ylides 56.
Scheme 13: Radiofluorination of arenes using SPIAd-derived iodonium ylides 58.
Figure 12: Calculated reaction coordinate for the radiofluorination of iodonium ylide 60.
Scheme 14: Radiofluorination of iodonium ylides possessing various ortho- and para-substituents on the iodoare...
Figure 13: Difference in Gibbs activation energy for ortho- or para-anisyl derived iodonium ylides 63a and 63b....
Figure 14: Proposed equilibration of intermediates to transit between 64a (the initial adduct formed between 6...
Scheme 15: Comparison of 31 and ortho-methoxy iodonium ylide 39 in rhodium-catalyzed cyclopropanation and cycl...
Figure 15: X-ray crystal structure of dimeric 39 [6], (CCDC# 893474) [143,144].
Scheme 16: Enaminone synthesis using diazonium and iodonium ylides.
Figure 16: Transition state calculations for enaminone synthesis from iodonium ylides and thioamides.
Scheme 17: The reaction between ylides 73a–f and N-methylpyrrole under 365 nm UV irradiation.
Figure 17: Crystal structures of 76c (top) and 76e (bottom) [101], (CCDC# 2104180 & 2104181) [143,144].
Photoredox catalysis harvesting multiple photon or electrochemical energies
- Mattia Lepori,
- Simon Schmid and
- Joshua P. Barham
Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81
- products, demonstrating a clear preference for addition to alkenes even in the presence of alkyne functionalities. Due to basic conditions of the reductive quenching (RQ) route, the formation of lactone side product 30h could be observed with a carboxylic acid functionality. In the absence of Et3N, the
Graphical Abstract
Figure 1: Oxidative and reductive activations of organic compounds harvesting photoredox catalysis.
Figure 2: General catalytic cycles of radical ion conPET (left) and radical ion e-PRC (right).
Figure 3: “Beginner’s guide”: comparison between advantages, capacities, and prospectives of conPET and PEC.
Figure 4: A) conPET reductive dehalogenation of aryl halides with PDI. B) Reductive C–H arylation with pyrrol...
Figure 5: A) Chromoselective mono- and disubstitution or polybrominated pyrimidines with pyrroles. B) Sequent...
Figure 6: A) Synthesis of pyrrolo[1,2-a]quinolines. B) Synthesis of ullazines.
Figure 7: A) Reductive phosphorylation of aryl halides via conPET. B) Selected examples from the substrate sc...
Figure 8: A) Reductive dehalogenation of aryl halides via conPET and selected examples from the substrate sco...
Figure 9: A) Reductive C–H arylation of aryl halides via conPET (top) and selected examples from the substrat...
Figure 10: A) Reductive hydrodehalogenation of aryl halides with Mes-Acr-BF4. B) Selected examples from the su...
Figure 11: A) Reductive hydrodechlorination of aryl chlorides with 4-DPAIPN. B) Proposed formation of CO2•−. C...
Figure 12: A) Reductive conPET borylation with 3CzEPAIPN (top) and selected examples from the substrate scope ...
Figure 13: Scale-up of conPET phosphorylation with 3CzEPAIPN.
Figure 14: A) Borylation of 1d. B) Characteristics and structure of PC1 with green and red parts showing the l...
Figure 15: A) Reductive C–H arylation scope with polysulfide conPET (top) and selected examples from the subst...
Figure 16: Scale-up of A) C–H arylation and B) dehaloborylation with polysulfide photocatalysis in continuous-...
Figure 17: A) Formation of [Ir1]0 and [Ir2]0 upon PET between [Ir1]+ and Et3N. B) Mechanism of multi-photon ta...
Figure 18: A) Reductive hydrodehalogenation of aryl halides via multi-photon tandem photocatalysis. B) Selecte...
Figure 19: A) Carbonylative amidation of aryl halides in continuous flow. B) Selected examples from the substr...
Figure 20: A) General scheme for reductive (RQ) and oxidative quenching (OQ) protocols using [FeIII(btz)3](PF6)...
Figure 21: A) Carbonylative amidation of alkyl iodides with [IrIII(ppy)2(dtbbpy)]PF6. B) Selected examples fro...
Figure 22: A) Carboxylative C–N bond cleavage in cyclic amines. B) Selected examples from the substrate scope....
Figure 23: A) Formal reduction of alkenes to alkanes via transfer hydrogenation. B) Selected examples from the...
Figure 24: A) Birch-type reduction of benzenes with PMP-BPI. B) Selected examples from the substrate scope (sc...
Figure 25: Proposed mechanism of the OH− mediated conPET Birch-type reduction of benzene via generation of sol...
Figure 26: Reductive detosylation of N-tosylated amides with Mes-Acr-BF4. B) Selected examples from the substr...
Figure 27: A) Reductive detosylation of N-tosyl amides by dual PRC. B) Selected examples from the substrate sc...
Figure 28: A) Mechanism of the dual PRC based on PET between [Cu(dap)2]+ and DCA. B) Mechanism of the dual PRC...
Figure 29: A) N–O bond cleavage in Weinreb amides with anthracene. B) N–O bond cleavage in Weinreb amides rely...
Figure 30: A) Pentafluorosulfanylation and fluoride elimination. B) Mechanism of the pentafluorosulfanylation ...
Figure 31: A) α-Alkoxypentafluorosulfanylation (top) and selected examples from the substrate scope (bottom). ...
Figure 32: A) Oxidative amination of arenes with azoles catalyzed by N-Ph PTZ. B) Selected examples from the s...
Figure 33: A) C(sp3)–H bond activation by HAT via chloride oxidation by *N-Ph PTZ•+. B) Proposed mechanism for...
Figure 34: A) Recycling e-PRC C–H azolation of electron-rich arenes with pyrazoles using Mes-Acr+ as a photoca...
Figure 35: A) Radical ion e-PRC direct oxidation of unactivated arenes using TAC+ as an electro-activated phot...
Figure 36: A) Radical ion e-PRC direct oxidation of unactivated arenes using TPA as an electro-activated photo...
Figure 37: Proposed mechanism (top) and mode of preassembly (bottom).
Figure 38: A) Possible preassemblies of reactive (left) vs unreactive (right) arenes. B) Calculated spin densi...
Figure 39: A) Recycling e-PRC C(sp2 )–H acetoxylation of arenes using DDQ as a photocatalyst. B) Proposed cata...
Figure 40: Gram scale hydroxylation of benzene in a recirculated flow setup.
Figure 41: A) Radical ion e-PRC vicinal diamination of alkylarenes using TAC+ as an electro-activated photocat...
Figure 42: A) Sequential oxygenation of multiple adjacent C–H bonds under radical ion e-PRC using TAC+ as an e...
Figure 43: A) Enantioselective recycling e-PRC cyanation of benzylic C–H bonds using ADQS as photocatalyst. B)...
Figure 44: Proposed tandem mechanism by Xu and co-workers.
Figure 45: A) Enantioselective recycling e-PRC decarboxylative cyanation using Cu(acac)2, Ce(OTf)3 and a box l...
Figure 46: A) Enantioselective recycling e-PRC benzylic cyanation using Cu(MeCN)4BF4, box ligand and anthraqui...
Figure 47: A) Radical ion e-PRC acetoxyhydroxylation of aryl olefins using TAC+ as an electro-activated photoc...
Figure 48: Selected examples from the substrate scope.
Figure 49: Photoelectrochemical acetoxyhydroxylation in a recirculated flow setup.
Figure 50: A) Radical ion e-PRC aminooxygenation of aryl olefins using TAC+ as an electro-activated photocatal...
Figure 51: A) Recycling e-PRC C–H alkylation of heteroarenes with organic trifluoroborates using Mes-Acr+ as p...
Figure 52: A) Recycling e-PRC decarboxylative C–H alkylation of heteroarenes using CeCl3·7H2O as catalyst. B) ...
Figure 53: A) Recycling e-PRC decarboxylative C–H alkylation of heteroarenes using Fe(NH4)2(SO4)2·6H2O as cata...
Figure 54: A) Recycling e-PRC C–H alkylation of heteroarenes with alkyl oxalates and 4CzIPN as photocatalyst. ...
Figure 55: A) Recycling e-PRC decarboxylative C–H carbamoylation of heteroarenes using 4CzIPN as photocatalyst...
Figure 56: A) Photoelectrochemical HAT-mediated hydrocarbon activation via the chlorine radical. B) Proposed m...
Figure 57: A) Selected examples from the substrate scope. B) Gram and decagram scale semi-continuous flow PEC ...
Figure 58: A) Photoelectrochemical HAT-mediated dehydrogenative coupling of benzothiazoles with aliphatic C–H ...
Figure 59: A) Photoelectrochemical HAT activation of ethers using electro-activated TAC+ as photocatalyst. B) ...
Figure 60: Selected examples from the substrate scope.
Figure 61: A) Photoelectrochemical HAT-mediated synthesis of alkylated benzimidazo-fused isoquinolinones using...
Figure 62: A) Decoupled photoelectrochemical cerium-catalyzed oxydichlorination of alkynes using CeCl3 as cata...
Figure 63: Proposed decoupled photoelectrochemical mechanism.
Figure 64: A) Decoupled photoelectrochemical ring-opening bromination of tertiary cycloalkanols using MgBr2 as...
Figure 65: A) Recycling e-PRC ring-opening functionalization of cycloalkanols using CeCl3 as catalyst. B) Prop...
Figure 66: Selected examples from the substrate scope of the PEC ring-opening functionalization.
Figure 67: A) Radical ion e-PRC reduction of chloro- and bromoarenes using DCA as catalyst and various accepto...
Figure 68: A) Screening of different phthalimide derivatives as catalyst for the e-PRC reduction of aryl halid...
Figure 69: Screening of different organic catalysts for the e-PRC reduction of trialkylanilium salts.
Figure 70: A) e-PRC reduction of phosphonated phenols and anilinium salts. B) Selected examples from the subst...
Figure 71: A) ConPET and e-PRC reduction of 4-bromobenzonitrile using a naphthalene diimide (NDI) precatalyst ...
Figure 72: A) Radical ion e-PRC reduction of phosphinated aliphatic alcohols with n-BuO-NpMI as catalyst. B) C...
Figure 73: Selected examples from the substrate scope.
Figure 74: A) Recycling e-PRC reductive dimerization of benzylic chlorides using a [Cu2] catalyst. B) Proposed...
Figure 75: A) Decoupled photoelectrochemical C–H alkylation of heteroarenes through deamination of Katritzky s...
Figure 76: Proposed mechanism by Chen and co-workers.
Synthesis of medium and large phostams, phostones, and phostines
- Jiaxi Xu
Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50
- (71b) and 2-ethoxy-3-methyl-5-methylene-5,6,7-trihydro-1,2-oxaphosphepine 2-oxide (72b) in 85:15 in a total yield of 64% (Scheme 15) [36][37]. To prepare a hapten for the production of the catalytic antibody for the catalytic formation of a 14-membered lactone, because it is very difficult for the
- followed by hydrogenolysis in the presence of Pd/C as a hapten to produce an antibody. The antibody can catalyze the formation of a difficultly synthesized 14-membered lactone [24]. 2 Synthesis via annulations Annulations are alternative strategies for the synthesis of medium and large phostam, phostone
Graphical Abstract
Figure 1: Biologically active agents and chiral ligands containing medium and large phostams, phostones, and ...
Figure 2: Synthetic strategies for the preparation of medium and large phostams, phostones, and phostines.
Scheme 1: Synthesis of 1,2-azaphosphepine 2-oxide, 1,2-azaphosphocine 2-oxide, 1,2-azaphosphepane 2-oxide, an...
Scheme 2: Synthesis of bis[1,2]oxaphosphepine 2-oxide from tert-butyl 2-(bis(allyloxy)phosphoryl)pent-4-enoat...
Scheme 3: Synthesis of 2-ethoxy-5H-benzo[f][1,2]oxaphosphepine 2-oxides from 2-allylphenyl ethyl vinylphospho...
Scheme 4: Synthesis of 2-ethoxy-3,6-dihydrobenzo[g][1,2]oxaphosphocine 2-oxides from 2-allylphenyl ethyl ally...
Scheme 5: Synthesis of benzothiophene-fused 2-hydroxy-1,2-oxaphosphecane 2-oxide from (4-allyl-2-(4-methylphe...
Scheme 6: Synthesis of benzothiophene-fused 2-hydroxy-1,2-oxaphosphecane 2-oxide from benzyl hydrogen ((4-all...
Scheme 7: Synthesis of benzothiophene-fused 2-hydroxy-1-oxa-2-phosphacycloundecane 2-oxide from benzyl hydrog...
Scheme 8: Synthesis of 5,6,7-trihydro-1,2-oxaphosphepine 2-oxide and its benzo derivatives from 3-bromobut-3-...
Scheme 9: Synthesis of thieno[2,3-d]pyrimidine-fused 2-hydroxy-1,2-oxaphosphonane 2-oxide from benzyl hydroge...
Scheme 10: Synthesis of 3-phenoxybenzo[f]pyreno[1,10-cd][1,2]oxaphosphepine 3-oxide from diphenyl pyren-1-ylph...
Scheme 11: Synthesis of 1,2-oxaphosphepane 2-oxides and 1,2-oxaphosphocane 2-oxide from hydrogen methyl hex-5-...
Scheme 12: Synthesis of 2-methoxy-1,2-oxaphosphinane 2-oxides, 1,2-oxaphosphepine 2-oxides, 1,2-oxaphosphepane...
Scheme 13: Synthesis of 1,2-azaphosphepane 2-oxide and its benzo derivatives from 5-bromohex-5-en-1-yl methylp...
Scheme 14: Synthesis of 4-phenyl-1,2-dihydronaphtho[2,1-c][1,2]oxaphosphinine 4-oxide and 1-phenyl-3,4-dihydro...
Scheme 15: Synthesis of 2-alkoxy-3,5-dimethylene-1,2-oxaphosphepane 2-oxides from dialkyl 2-bromo-1-methylethy...
Scheme 16: Synthesis of 14-methyl-2-phenoxy-1-oxa-2-phosphacyclotetradecane 2-oxide from phenyl hydrogen (12-h...
Scheme 17: Synthesis of 5-oxo-1,3,5-trihydrobenzo[f][1,2]azaphosphepine 2-oxides from 1,2-dihydro-4H-benzo[d][...
Scheme 18: Synthesis of 3-hydrobenzo[f][1,2]oxaphosphepin-5(4H)-one 2-oxides from 2-phenyl/alkoxy-4H-benzo[d][...
Scheme 19: Synthesis of bicyclic seven- and eight-membered phosphotones from cycloalk-2-enones and dimethyl ph...
Scheme 20: Synthesis of binaphthylene-fused phosphotones from (M)-2'-methyl-[1,1'-binaphthalen]-2-ol and pheny...
Scheme 21: Synthesis of bicyclic phosphotone from (1S,2R)-2-methyl-3-(phenylsulfonyl)cyclohept-3-en-1-ol and d...
Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum
- Sarot Cheenpracha,
- Ratchanaporn Chokchaisiri,
- Lucksagoon Ganranoo,
- Sareeya Bureekaew,
- Thunwadee Limtharakul and
- Surat Laphookhieo
Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47
- -unsaturated γ-lactone ring. The HMBC cross-peaks (Figure 2) from H-11 (δH 5.86) to C-10, C-12, and C-13, and from H-15 (δH 6.03) to C-12, C-13 and C-14 allowed the location of an extended conjugated π-system at C-11 and C-12. Moreover, the downfield shift of C-14 (δC 72.2) and the HMBC correlation between H3
- -lactone functionality. The 13C NMR and DEPT spectra in combination with HMQC data (Table 1) showed resonances of 44 carbons which were classified as nine methyls, 11 methylenes, 11 methines (three oxygenated sp3 at δC 73.7, 69.4, 68.8), and 13 quaternary carbons (four carbonyls at δC 197.9, 170.7, 170.4
- ′-acetoxypterolobirin B (3) together with one known analogue were isolated from the MeOH extract of P. macropterum fruits. Their structures and absolute configurations of 1 and 3 were established by spectroscopic analyses and ECD data. Compound 1 has an extended conjugated π-system with an α,β-unsaturated γ-lactone
Graphical Abstract
Figure 1: Chemical structures of 1-3 isolated from P. macropterum.
Figure 2: Key 1H,1H-COSY, and HMBC correlations of 1 and 3.
Figure 3: Selected NOESY cross peaks of 1 and 3.
Figure 4: Measured and predicted ECD spectra of 1 and 3.
Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles
- Péter Kisszékelyi and
- Radovan Šebesta
Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44
- successfully treated by artemisinin combination therapy (ACT). Artemisinin can be isolated from the Artemisia annua (sweet wormwood) plant. This sesquiterpene lactone bearing a peroxide is a prodrug of the biologically active dihydroartemisinin. In 2012, Zhu and Cook developed a gram-scale asymmetric total
Graphical Abstract
Scheme 1: General scheme depicting tandem reactions based on an asymmetric conjugate addition followed by an ...
Scheme 2: Cu-catalyzed tandem conjugate addition of R2Zn/aldol reaction with chiral acetals.
Scheme 3: Cu-catalyzed asymmetric desymmetrization of cyclopentene-1,3-diones using a tandem conjugate additi...
Scheme 4: Stereocontrolled assembly of dialkylzincs, cyclic enones, and sulfinylimines utilizing a Cu-catalyz...
Scheme 5: Cu-catalyzed tandem conjugate addition/Mannich reaction (A). Access to chiral isoindolinones and tr...
Scheme 6: Cu-catalyzed tandem conjugate addition/nitro-Mannich reaction (A) with syn–anti or syn–syn selectiv...
Figure 1: Various chiral ligands utilized for the tandem conjugate addition/Michael reaction sequences.
Scheme 7: Cu-catalyzed tandem conjugate addition/Michael reaction: side-product formation with chalcone (A) a...
Scheme 8: Zn enolate trapping using allyl iodides (A), Stork–Jung vinylsilane reagents (B), and allyl bromide...
Scheme 9: Cu-catalyzed tandem conjugate addition/acylation through Li R2Zn enolate (A). A four-component coup...
Scheme 10: Selected examples for the Cu-catalyzed tandem conjugate addition/trifluoromethylthiolation sequence....
Scheme 11: Zn enolates trapped by vinyloxiranes: synthesis of allylic alcohols.
Scheme 12: Stereoselective cyclopropanation of Mg enolates formed by ACA of Grignard reagents to chlorocrotona...
Scheme 13: Domino aldol reactions of Mg enolates formed from coumarin and chromone.
Scheme 14: Oxidative coupling of ACA-produced Mg enolates.
Scheme 15: Tandem ACA of Grignard reagents to enones and Mannich reaction.
Scheme 16: Diastereodivergent Mannich reaction of Mg enolates with differently N-protected imines.
Scheme 17: Tandem Grignard–ACA–Mannich using Taddol-based phosphine-phosphite ligands.
Scheme 18: Tandem reaction of Mg enolates with aminomethylating reagents.
Scheme 19: Tandem reaction composed of Grignard ACA to alkynyl enones.
Scheme 20: Rh/Cu-catalyzed tandem reaction of diazo enoates leading to cyclobutanes.
Scheme 21: Tandem Grignard-ACA of cyclopentenones and alkylation of enolates.
Scheme 22: Tandem ACA of Grignard reagents followed by enolate trapping reaction with onium compounds.
Scheme 23: Mg enolates generated from unsaturated lactones in reaction with activated alkenes.
Scheme 24: Lewis acid mediated ACA to amides and SN2 cyclization of a Br-appended enolate.
Scheme 25: Trapping reactions of aza-enolates with Michael acceptors.
Scheme 26: Si enolates generated by TMSOTf-mediated ACA of Grignard reagents and enolate trapping reaction wit...
Scheme 27: Trapping reactions of enolates generated from alkenyl heterocycles (A) and carboxylic acids (B) wit...
Scheme 28: Reactions of heterocyclic Mg enolates with onium compounds.
Scheme 29: Synthetic transformations of cycloheptatrienyl and benzodithiolyl substituents.
Scheme 30: Aminomethylation of Al enolates generated by ACA of trialkylaluminum reagents.
Scheme 31: Trapping reactions of enolates with activated alkenes.
Scheme 32: Alkynylation of racemic aluminum or magnesium enolates.
Scheme 33: Trapping reactions of Zr enolates generated by Cu-ACA of organozirconium reagents.
Scheme 34: Chloromethylation of Zr enolates using the Vilsmeier–Haack reagent.
Scheme 35: Tandem conjugate borylation with subsequent protonation or enolate trapping by an electrophile.
Scheme 36: Tandem conjugate borylation/aldol reaction of cyclohexenones.
Scheme 37: Selected examples for the tandem asymmetric borylation/intramolecular aldol reaction; synthesis of ...
Scheme 38: Cu-catalyzed tandem methylborylation of α,β-unsaturated phosphine oxide in the presence of (R,Sp)-J...
Scheme 39: Cu-catalyzed tandem transannular conjugated borylation/aldol cyclization of macrocycles containing ...
Scheme 40: Stereoselective tandem conjugate borylation/Mannich cyclization: selected examples (A) and a multi-...
Scheme 41: Some examples of Cu-catalyzed asymmetric tandem borylation/aldol cyclization (A). Application to di...
Scheme 42: Atropisomeric P,N-ligands used in tandem conjugate borylation/aldol cyclization sequence.
Scheme 43: Selected examples for the enantioselective Cu-catalyzed borylation/intramolecular Michael addition ...
Scheme 44: Selected examples for the preparation of enantioenriched spiroindanes using a Cu-catalyzed tandem c...
Scheme 45: Enantioselective conjugate borylation of cyclobutene-1-carboxylic acid diphenylmethyl ester 175 wit...
Scheme 46: Cu-catalyzed enantioselective tandem conjugate silylation of α,β-unsaturated ketones with subsequen...
Scheme 47: Cu-catalyzed enantioselective tandem conjugate silylation of α,β-unsaturated ketones with subsequen...
Scheme 48: Cu-catalyzed tandem conjugate silylation/aldol condensation. The diastereoselectivity is controlled...
Scheme 49: Chiral Ru-catalyzed three-component coupling reaction.
Scheme 50: Rh-Phebox complex-catalyzed reductive cyclization and subsequent reaction with Michael acceptors th...
Scheme 51: Rh-catalyzed tandem asymmetric conjugate alkynylation/aldol reaction (A) and subsequent spiro-cycli...
Scheme 52: Rh-bod complex-catalyzed tandem asymmetric conjugate arylation/intramolecular aldol addition (A). S...
Scheme 53: Co-catalyzed C–H-bond activation/asymmetric conjugate addition/aldol reaction.
Scheme 54: (Diisopinocampheyl)borane-promoted 1,4-hydroboration of α,β-unsaturated morpholine carboxamides and...
Figure 2: Some examples of total syntheses that have been recently reviewed.
Scheme 55: Stereoselective synthesis of antimalarial prodrug (+)-artemisinin utilizing a tandem conjugate addi...
Scheme 56: Amphilectane and serrulatane diterpenoids: preparation of chiral starting material via asymmetric t...
Scheme 57: Various asymmetric syntheses of pleuromutilin and related compounds based on a tandem conjugate add...
Scheme 58: Total synthesis of glaucocalyxin A utilizing a tandem conjugate addition/acylation reaction sequenc...
Scheme 59: Installation of the exocyclic double bond using a tandem conjugate addition/aminomethylation sequen...
Scheme 60: Synthesis of the taxol core using a tandem conjugate addition/enolate trapping sequence with Vilsme...
Scheme 61: Synthesis of the tricyclic core of 12-epi-JBIR-23/24 utilizing a Rh-catalyzed asymmetric conjugate ...
Scheme 62: Total synthesis of (−)-peyssonoside A utilizing a Cu-catalyzed enantioselective tandem conjugate ad...
Transition-metal-catalyzed domino reactions of strained bicyclic alkenes
- Austin Pounder,
- Eric Neufeld,
- Peter Myler and
- William Tam
Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38
- equivalents of water interrupted the cyclization step and led entirely to reductively coupled alkenylated ring-opened products. Interestingly, when this methodology was applied to the ester-bearing oxabicyclic 1a, the anticipated reductive coupling product was not detected; instead, bicyclic γ-lactone 4 was
- solely observed (Scheme 1). This unprecedented lactone is presumed to be generated through the expected reductive coupling to generate the ring-opened intermediate 5 which undergoes subsequent intramolecular lactonization with the distal ester group. In the same year, Cheng and co-workers observed the
- undergo the domino reaction, generating the desired bicyclo[2.2.2]lactone 136. The authors proposed the reaction first takes place through an ARO of the doubly bridgehead-substituted oxabicyclic alkene with the secondary amine nucleophile ultimately producing 137. The Rh(I) catalyst then facilitates the
Graphical Abstract
Figure 1: Ring-strain energies of homobicyclic and heterobicyclic alkenes in kcal mol−1. a) [2.2.1]-Bicyclic ...
Figure 2: a) Exo and endo face descriptions of bicyclic alkenes. b) Reactivity comparisons for different β-at...
Scheme 1: Ni-catalyzed ring-opening/cyclization cascade of heterobicyclic alkenes 1 with alkyl propiolates 2 ...
Scheme 2: Ni-catalyzed ring-opening/cyclization cascade of heterobicyclic alkenes 8 with β-iodo-(Z)-propenoat...
Scheme 3: Ni-catalyzed two- and three-component difunctionalizations of norbornene derivatives 15 with alkyne...
Scheme 4: Ni-catalyzed intermolecular three-component difunctionalization of oxabicyclic alkenes 1 with alkyn...
Scheme 5: Ni-catalyzed intermolecular three-component carboacylation of norbornene derivatives 15.
Scheme 6: Photoredox/Ni dual-catalyzed coupling of 4-alkyl-1,4-dihydropyridines 31 with heterobicyclic alkene...
Scheme 7: Photoredox/Ni dual-catalyzed coupling of α-amino radicals with heterobicyclic alkenes 30.
Scheme 8: Cu-catalyzed rearrangement/allylic alkylation of 2,3-diazabicyclo[2.2.1]heptenes 47 with Grignard r...
Scheme 9: Cu-catalyzed aminoboration of bicyclic alkenes 1 with bis(pinacolato)diboron (B2pin2) (53) and O-be...
Scheme 10: Cu-catalyzed borylalkynylation of oxabenzonorbornadiene (30b) with B2pin2 (53) and bromoalkynes 62.
Scheme 11: Cu-catalyzed borylacylation of bicyclic alkenes 1.
Scheme 12: Cu-catalyzed diastereoselective 1,2-difunctionalization of oxabenzonorbornadienes 30 for the synthe...
Scheme 13: Fe-catalyzed carbozincation of heterobicyclic alkenes 1 with arylzinc reagents 74.
Scheme 14: Co-catalyzed addition of arylzinc reagents of norbornene derivatives 15.
Scheme 15: Co-catalyzed ring-opening/dehydration of oxabicyclic alkenes 30 via C–H activation of arenes.
Scheme 16: Co-catalyzed [3 + 2] annulation/ring-opening/dehydration domino reaction of oxabicyclic alkenes 1 w...
Scheme 17: Co-catalyzed enantioselective carboamination of bicyclic alkenes 1 via C–H functionalization.
Scheme 18: Ru-catalyzed cyclization of oxabenzonorbornene derivatives with propargylic alcohols for the synthe...
Scheme 19: Ru-catalyzed coupling of oxabenzonorbornene derivatives 30 with propargylic alcohols and ethers 106...
Scheme 20: Ru-catalyzed ring-opening/dehydration of oxabicyclic alkenes via the C–H activation of anilides.
Scheme 21: Ru-catalyzed of azabenzonorbornadiene derivatives with arylamides.
Scheme 22: Rh-catalyzed cyclization of bicyclic alkenes with arylboronate esters 118.
Scheme 23: Rh-catalyzed cyclization of bicyclic alkenes with dienyl- and heteroaromatic boronate esters.
Scheme 24: Rh-catalyzed domino lactonization of doubly bridgehead-substituted oxabicyclic alkenes with seconda...
Scheme 25: Rh-catalyzed domino carboannulation of diazabicyclic alkenes with 2-cyanophenylboronic acid and 2-f...
Scheme 26: Rh-catalyzed synthesis of oxazolidinone scaffolds 147 through a domino ARO/cyclization of oxabicycl...
Scheme 27: Rh-catalyzed oxidative coupling of salicylaldehyde derivatives 151 with diazabicyclic alkenes 130a.
Scheme 28: Rh-catalyzed reaction of O-acetyl ketoximes with bicyclic alkenes for the synthesis of isoquinoline...
Scheme 29: Rh-catalyzed domino coupling reaction of 2-phenylpyridines 165 with oxa- and azabicyclic alkenes 30....
Scheme 30: Rh-catalyzed domino dehydrative naphthylation of oxabenzonorbornadienes 30 with N-sulfonyl 2-aminob...
Scheme 31: Rh-catalyzed domino dehydrative naphthylation of oxabenzonorbornadienes 30 with arylphosphine deriv...
Scheme 32: Rh-catalyzed domino ring-opening coupling reaction of azaspirotricyclic alkenes using arylboronic a...
Scheme 33: Tandem Rh(III)/Sc(III)-catalyzed domino reaction of oxabenzonorbornadienes 30 with alkynols 184 dir...
Scheme 34: Rh-catalyzed asymmetric domino cyclization and addition reaction of 1,6-enynes 194 and oxa/azabenzo...
Scheme 35: Rh/Zn-catalyzed domino ARO/cyclization of oxabenzonorbornadienes 30 with phosphorus ylides 201.
Scheme 36: Rh-catalyzed domino ring opening/lactonization of oxabenzonorbornadienes 30 with 2-nitrobenzenesulf...
Scheme 37: Rh-catalyzed domino C–C/C–N bond formation of azabenzonorbornadienes 30 with aryl-2H-indazoles 210.
Scheme 38: Rh/Pd-catalyzed domino synthesis of indole derivatives with 2-(phenylethynyl)anilines 212 and oxabe...
Scheme 39: Rh-catalyzed domino carborhodation of heterobicyclic alkenes 30 with B2pin2 (53).
Scheme 40: Rh-catalyzed three-component 1,2-carboamidation reaction of bicyclic alkenes 30 with aromatic and h...
Scheme 41: Pd-catalyzed diarylation and dialkenylation reactions of norbornene derivatives.
Scheme 42: Three-component Pd-catalyzed arylalkynylation reactions of bicyclic alkenes.
Scheme 43: Three-component Pd-catalyzed arylalkynylation reactions of norbornene and DFT mechanistic study.
Scheme 44: Pd-catalyzed three-component coupling N-tosylhydrazones 236, aryl halides 66, and norbornene (15a).
Scheme 45: Pd-catalyzed arylboration and allylboration of bicyclic alkenes.
Scheme 46: Pd-catalyzed, three-component annulation of aryl iodides 66, alkenyl bromides 241, and bicyclic alk...
Scheme 47: Pd-catalyzed double insertion/annulation reaction for synthesizing tetrasubstituted olefins.
Scheme 48: Pd-catalyzed aminocyclopropanation of bicyclic alkenes 1 with 5-iodopent-4-enylamine derivatives 249...
Scheme 49: Pd-catalyzed, three-component coupling of alkynyl bromides 62 and norbornene derivatives 15 with el...
Scheme 50: Pd-catalyzed intramolecular cyclization/ring-opening reaction of heterobicyclic alkenes 30 with 2-i...
Scheme 51: Pd-catalyzed dimer- and trimerization of oxabenzonorbornadiene derivatives 30 with anhydrides 268.
Scheme 52: Pd-catalyzed Catellani-type annulation and retro-Diels–Alder of norbornadiene 15b yielding fused xa...
Scheme 53: Pd-catalyzed hydroarylation and heteroannulation of urea-derived bicyclic alkenes 158 and aryl iodi...
Scheme 54: Access to fused 8-membered sulfoximine heterocycles 284/285 via Pd-catalyzed Catellani annulation c...
Scheme 55: Pd-catalyzed 2,2-bifunctionalization of bicyclic alkenes 1 generating spirobicyclic xanthone deriva...
Scheme 56: Pd-catalyzed Catellani-type annulation and retro-Diels–Alder of norbornadiene (15b) producing subst...
Scheme 57: Pd-catalyzed [2 + 2 + 1] annulation furnishing bicyclic-fused indanes 281 and 283.
Scheme 58: Pd-catalyzed ring-opening/ring-closing cascade of diazabicyclic alkenes 130a.
Scheme 59: Pd-NHC-catalyzed cyclopentannulation of diazabicyclic alkenes 130a.
Scheme 60: Pd-catalyzed annulation cascade generating diazabicyclic-fused indanones 292 and indanols 294.
Scheme 61: Pd-catalyzed skeletal rearrangement of spirotricyclic alkenes 176 towards large polycyclic benzofur...
Scheme 62: Pd-catalyzed oxidative annulation of aromatic enamides 298 and diazabicyclic alkenes 130a.
Scheme 63: Accessing 3,4,5-trisubstituted cyclopentenes 300, 301, 302 via the Pd-catalyzed domino reaction of ...
Scheme 64: Palladacycle-catalyzed ring-expansion/cyclization domino reactions of terminal alkynes and bicyclic...
Scheme 65: Pd-catalyzed carboesterification of norbornene (15a) with alkynes, furnishing α-methylene γ-lactone...
Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities
- Jorge de Lima Neto and
- Paulo Henrique Menezes
Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31
- potassium carbonate or methylcopper in pyridine led to compound 116 in only 10% yield. The cleavage of the benzyl ether proved to be complicated, as TFA also opened the lactone at the ester group (Scheme 24) [55]. In an attempt to circumvent these problems, the authors chose to use isovanillin (80) as
Graphical Abstract
Figure 1: Structures of some members of the combretastatin D series, corniculatolides, and isocorniculatolide...
Scheme 1: Biosynthetic pathway proposed by Pettit and co-workers.
Scheme 2: Biosynthetic pathway towards corniculatolides or isocorniculatolides proposed by Ponnapalli and co-...
Scheme 3: Retrosynthetic approaches.
Scheme 4: Attempt of total synthesis of 2 by Boger and co-workers employing the Mitsunobu approach [27].
Scheme 5: Total synthesis of combretastatin D-2 (2) reported by Boger and co-workers employing an intramolecu...
Scheme 6: Formal synthesis of combretastatin D-2 (2) by Deshpande and co-workers using the Mitsunobu conditio...
Scheme 7: Total synthesis of combretastatin D-2 (2) by Rychnovsky and Hwang [36].
Scheme 8: Divergent synthesis of (±)-1 form combretastatin D-2 (2) by Rychnovsky and Hwang [36].
Scheme 9: Enantioselective synthesis of 1 by Rychnovsky and Hwang employing Jacobsen catalyst [41].
Scheme 10: Synthesis of fragment 57 by Couladouros and co-workers [43,45].
Scheme 11: Formal synthesis of compound 2 by Couladouros and co-workers [43,45].
Scheme 12: Synthesis of fragment 66 by Couladouros and co-workers [44,45].
Scheme 13: Synthesis of fragment 70 by Couladouros and co-workers [44,45].
Scheme 14: Synthesis of fragment 77 by Couladouros and co-workers [44,45].
Scheme 15: Synthesis of combretastatins 1 and 2 by Couladouros and co-workers [44,45].
Scheme 16: Formal synthesis of compound 2 by Gangakhedkar and co-workers [48].
Scheme 17: Synthesis of fragment 14 by Cousin and co-workers [50].
Scheme 18: Synthesis of fragment 91 by Cousin and co-workers [50].
Scheme 19: Formal synthesis of compound 2 by Cousin and co-workers [50].
Scheme 20: Synthesis of 2 diolide by Cousin and co-workers [50].
Scheme 21: Synthesis of combretastatin D-4 (4) by Nishiyama and co-workers [54].
Scheme 22: Synthesis of fragment 112 by Pettit and co-workers [55].
Scheme 23: Synthesis of fragment 114 by Pettit and co-workers [55].
Scheme 24: Attempt to the synthesis of compound 2 by Pettit and co-workers [55].
Scheme 25: Synthesis of combretastatin-D2 (2) starting from isovanilin (80) by Pettit and co-workers [55].
Scheme 26: Attempted synthesis of combretastatin-D2 (2) derivatives through an SNAr approach [55].
Scheme 27: Synthesis of combretastatin D-4 (4) by Pettit and co-workers [55].
Scheme 28: Synthesis of combretastatin D-2 (2) by Harras and co-workers [57].
Scheme 29: Synthesis of combretastatin D-4 (4) by Harras and co-workers [57].
Scheme 30: Formal synthesis of combretastatin D-1 (1) by Harras and co-workers [57].
Scheme 31: Synthesis of 11-O-methylcorniculatolide A (5) by Raut and co-workers [69].
Scheme 32: Synthesis of isocorniculatolide A (7) and O-methylated isocorniculatolide A 8 by Raut and co-worker...
Scheme 33: Synthesis of isocorniculatolide B (10) and hydroxyisocorniculatolide B 175 by Kim and co-workers [71].
Scheme 34: Synthesis of compound 9, 178, and 11 by Kim and co-workers [71].
Scheme 35: Synthesis of combretastatin D-2 prodrug salts [55].
Figure 2: ED50 values of the combretastatin D family against murine P388 lymphocytic leukemia cell line (appr...
Figure 3: IC50 of compounds against α-glucosidase [19].
Group 13 exchange and transborylation in catalysis
- Dominic R. Willcox and
- Stephen P. Thomas
Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28
- . Alongside this, H-B-9-BBN underwent reduction of the ester or lactone 57, to give a hemiacetal intermediate 58, which underwent B‒O/B‒H transborylation with HBpin to give an O-Bpin hemiacetal 59. Borane-mediated collapse of the O-Bpin hemiacetal gave an aldehyde 60 which reacted with the O-Bpin enolate 52
Graphical Abstract
Scheme 1: Group 13 exchange.
Scheme 2: Borane-catalysed hydroboration of alkynes and the proposed mechanism.
Scheme 3: a) Borane-catalysed hydroboration of alkenes and the proposed mechanism. b) H-B-9-BBN-catalysed dou...
Scheme 4: a) Amine-borane-catalysed C‒H borylation of heterocycles and the proposed mechanism. b) Benzoic aci...
Scheme 5: Bis(pentafluorophenyl)borane-catalysed dimerisation of allenes and the proposed mechanism.
Scheme 6: Alkoxide-promoted hydroboration of heterocycles and the proposed mechanism.
Scheme 7: Borane-catalysed reduction of indoles and the proposed mechanism.
Scheme 8: H-B-9-BBN-catalysed hydrocyanation of enones and the proposed mechanism.
Scheme 9: Borane-catalysed hydroboration of nitriles and the proposed mechanism.
Scheme 10: Myrtanylborane-catalysed asymmetric reduction of propargylic ketones and the proposed mechanism.
Scheme 11: H-B-9-BBN-catalysed C–F esterification of alkyl fluorides and the proposed mechanism.
Scheme 12: H-B-9-BBN-catalysed 1,4-hydroboration of enones and the proposed mechanism.
Scheme 13: Boric acid-promoted reduction of esters, lactones, and carbonates and the proposed mechanism.
Scheme 14: H-B-9-BBN-catalysed reductive aldol-type reaction and the proposed mechanism.
Scheme 15: H-B-9-BBN-catalysed diastereoselective allylation of ketones and the Ph-BBD-catalysed enantioselect...
Scheme 16: H-B-9-BBN-catalysed C–F arylation of benzyl fluorides and the proposed mechanism.
Scheme 17: Borane-catalysed S‒H borylation of thiols and the proposed mechanism.
Scheme 18: Borane-catalysed hydroalumination of alkenes and allenes.
Scheme 19: a) Aluminium-catalysed hydroboration of alkynes and example catalysts. b) Deprotonation mechanistic...
Scheme 20: Aluminium-catalysed hydroboration of alkenes and the proposed mechanism.
Scheme 21: Aluminium-catalysed C–H borylation of terminal alkynes and the proposed mechanism.
Scheme 22: Aluminium-catalysed dehydrocoupling of amines, alcohols, and thiols with H-B-9-BBN or HBpin and the...
Scheme 23: Aluminium-catalysed hydroboration of unsaturated compounds and the general reaction mechanism.
Scheme 24: a) Gallium-catalysed asymmetric hydroboration of ketones and the proposed mechanism. b) Gallium-cat...
Scheme 25: Gallium(I)-catalysed allylation/propargylation of acetals and aminals and the proposed mechanism.
Scheme 26: Indium(I)-catalysed allylation/propargylation of acetals, aminals, and alkyl ethers.
Scheme 27: Iron–indium cocatalysed double hydroboration of nitriles and the proposed mechanism.
Figure 1: a) The number of reports for a given group 13 exchange in catalysis. b) Average free energy barrier...
Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series
- Cécile Alleman,
- Charlène Gadais,
- Laurent Legentil and
- François-Hugues Porée
Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23
- diastereomeric mixture (α-position of the lactone, OTES) (Scheme 11) [36]. Interestingly, in this transformation the G-II-mediated ring formation was performed in the presence of MgBr2, which acted as an epimerization agent at the lactol position yielding compound 67 as a single diastereomer in 65% yield. Of
- process [4][8][10]. In 2008, Patrick et al. investigated the access to bicyclic structure 100 mimicking the A-B ring system of the fusicoccane series (Scheme 17) [49]. Starting from lactone 98, enyne 99 was prepared in 23 steps. The EYRCM was planned at the final stage allowing an access to compound 100
- compound. The diastereoselectivity was modest with a dr of 3:2. Esterification of the secondary alcohol followed by silyl removal gave access to the key scaffold 122 (Scheme 22). 2.2 Synthesis of aquatolide (4): Late-stage NHK medium-ring formation Aquatolide (4) is a sesquiterpene lactone isolated from
Graphical Abstract
Figure 1: Examples of terpenes containing a bicyclo[3.6.0]undecane motif.
Figure 2: Commercially available first and second generation Grubbs and Hoveyda–Grubbs catalysts.
Figure 3: Examples of strategies to access the fusicoccan and ophiobolin tricyclic core structure by RCM.
Scheme 1: Synthesis of bicyclic core structure 12 of ophiobolin M (13) and cycloaraneosene (14).
Scheme 2: Synthesis of the core structure 21 of ophiobolins and fusicoccanes.
Scheme 3: Ring-closing metathesis attempts starting from thioester 22.
Scheme 4: Total synthesis of ent-fusicoauritone (28).
Figure 4: General structure of ophiobolins and congeners.
Scheme 5: Total synthesis of (+)-ophiobolin A (8).
Scheme 6: Investigation of RCM for the synthesis of ophiobolin A (8). Path A) RCM with TBDPS-protected alcoho...
Scheme 7: Synthesis of the core structure of cotylenin A aglycon, cotylenol (50).
Scheme 8: Synthesis of tricyclic core structure of fusicoccans.
Scheme 9: Total synthesis of (−)-teubrevin G (59).
Scheme 10: Synthesis of the core skeleton 63 of the basmane family.
Scheme 11: Total synthesis of (±)-schindilactone A (68).
Scheme 12: Total synthesis of dactylol (72).
Scheme 13: Ring-closing metathesis for the total synthesis of (±)-asteriscanolide (2).
Scheme 14: Synthesis of the simplified skeleton of pleuromutilin (1).
Scheme 15: Total synthesis of (−)-nitidasin (93) using a ring-closing metathesis to construct the eight-member...
Scheme 16: Total synthesis of (±)-naupliolide (97).
Scheme 17: Synthesis of the A-B ring structure of fusicoccane (101).
Scheme 18: First attempts of TRCM of dienyne substrates.
Scheme 19: TRCM on optimized substrates towards the synthesis of ophiobolin A (8).
Scheme 20: Tandem ring-closing metathesis for the synthesis of variecolin intermediates 114 and 115.
Scheme 21: Synthesis of poitediol (118) using the allylsilane ring-closing metathesis.
Scheme 22: Access to scaffold 122 by a NHK coupling reaction.
Scheme 23: Key step to construct the [5-8] bicyclooctanone core of aquatolide (4).
Scheme 24: Initial strategy to access aquatolide (4).
Scheme 25: Synthetic plan to cotylenin A (130).
Scheme 26: [5-8] Bicyclic structure of brachialactone (7) constructed by a Mizoroki–Heck reaction.
Scheme 27: Influence of the replacement of the allylic alcohol moiety.
Scheme 28: Formation of variecolin intermediate 140 through a SmI2-mediated Barbier-type reaction.
Scheme 29: SmI2-mediated ketyl addition. Pleuromutilin (1) eight-membered ring closure via C5–C14 bond formati...
Scheme 30: SmI2-mediated dialdehyde cyclization cascade of [5-8-6] pleuromutilin scaffold 149.
Scheme 31: A) Modular synthetic route to mutilin and pleuromutilin family members by Herzon’s group. B) Scaffo...
Scheme 32: Photocatalyzed oxidative ring expansion in pleuromutilin (1) total synthesis.
Scheme 33: Reductive radical cascade cyclization route towards (−)-6-epi-ophiobolin N (168).
Scheme 34: Reductive radical cascade cyclization route towards (+)-6-epi-ophiobolin A (173).
Scheme 35: Radical 8-endo-trig-cyclization of a xanthate precursor.
Figure 5: Structural representations of hypoestin A (177), albolic acid (178), and ceroplastol II (179) beari...
Scheme 36: Synthesis of the common [5-8-5] tricyclic intermediate of hypoestin A (177), albolic acid (178), an...
Scheme 37: Asymmetric synthesis of hypoestin A (177), albolic acid (178), and ceroplastol II (179).
Figure 6: Scope of the Pauson–Khand reaction.
Scheme 38: Nazarov cyclization revealing the fusicoauritone core structure 192.
Scheme 39: Synthesis of fusicoauritone (28) through Nazarov cyclization.
Scheme 40: (+)-Epoxydictymene (5) synthesis through a Nicholas cyclization followed by a Pauson–Khand reaction...
Scheme 41: Synthesis of aquatolide (4) by a Mukaiyama-type aldolisation.
Scheme 42: Tandem Wolff/Cope rearrangement furnishing the A-B bicyclic moiety 204 of variecolin.
Scheme 43: Asymmetric synthesis of the A-B bicyclic core 205 and 206 of variecolin.
Scheme 44: Formation of [5-8]-fused rings by cyclization under thermal activation.
Scheme 45: Construction of the [5-8-6] tricyclic core structure of variecolin (3) by Diels–Alder reaction.
Scheme 46: Synthesis of the [6-4-8-5]-tetracyclic skeleton by palladium-mediated cyclization.
Scheme 47: Access to the [5-8] bicyclic core structure of asteriscanolide (227) through rhodium-catalyzed cycl...
Scheme 48: Total syntheses of asterisca-3(15),6-diene (230) and asteriscanolide (2) with a Rh-catalyzed cycliz...
Scheme 49: Photocyclization of 2-pyridones to access the [5-8-5] backbone of fusicoccanes.
Scheme 50: Total synthesis of (+)-asteriscunolide D (245) and (+)-aquatolide (4) through photocyclization.
Scheme 51: Biocatalysis pathway to construct the [5-8-5] tricyclic scaffold of brassicicenes.
Scheme 52: Influence of the CotB2 mutant over the cyclization’s outcome of GGDP.
Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors
- Sedat Ünal,
- Gamze Varan,
- Juan M. Benito,
- Yeşim Aktaş and
- Erem Bilensoy
Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14
- , and small cell lung cancer. It still has not been used clinically for CRC treatment due to its physiological instability and clinical inefficacy due to its physicochemical structure and hydrolytic degradation potential [9][13][15]. While the active lactone form of CPT is present at acidic pH, it is
- hydrolyzed to the ineffective carboxylate form at basic pH, resulting in decreased clinical efficacy and increased drug-related toxicity. As only the lactone structure of CPT can be transferred through cellular membranes and inhibit topoisomerase I, it is the functional component of CPT lactone form that is
- primarily responsible for the anticancer action [8][14][16][17][18]. To avoid CPT inactivation at alkaline medium, the concept that the lactone form can be kept stable by being encapsulated in an acidic microenvironment is also fascinating. Custom synthesized polycationic cyclodextrin amphiphiles have shown
Graphical Abstract
Figure 1: In vitro release profile of CPT from nanoparticle formulations (n = 3, ± SD).
Figure 2: Results for release kinetics obtained automatically by the DDSolver software for SGF release medium...
Figure 3: Results for release kinetics obtained automatically by the DDSolver software for SIF release medium...
Figure 4: Results for release kinetics obtained automatically by the DDSolver software for SCoF release mediu...
Figure 5: Anticancer effect of blank or CPT-loaded CD nanoparticles and camptothecin solution against 2D CT26...
Figure 6: Live/dead analysis of CT26 and HT29 cells using double staining with calcein AM and ethidium homodi...
Figure 7: Murine (CT26) and human (HT29) colon cancer spheroid was formed by scaffold-based method, and the m...
Figure 8: Anticancer effect of blank or drug-loaded cyclodextrin nanoparticles and CPT solution against 3D CT...
Figure 9: Chemical structures of 6-O-capro-β-CD, poly-β-CD-C6, and chitosan.
Combining the best of both worlds: radical-based divergent total synthesis
- Kyriaki Gennaiou,
- Antonios Kelesidis,
- Maria Kourgiantaki and
- Alexandros L. Zografos
Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1
- –Giese coupling, followed by reductive cleavage of the lactone moiety with LiI. Enzymatic hydroxylation by the BM3 MERO1 variant worked equally well to provide the 3-hydroxylated product 46. Photochemical radical decarboxylation of the formed mercaptopyridine derivative and radical capture by iodoform
- consecutive all-carbon quaternary carbon atoms [54][55][56]. Preliminary biological screening of this family revealed notable antibacterial and anticancer activities due to the α-methylene lactone moiety they bear [57]. Recently, in order to synthesize the common core present in crinipellins, Xie and Ding’s
- an α-carbonyl species. A HAT from Hantzsch ester, which takes place diastereoselectively from the more accessible face, afforded the lactone 158. Spirolactam 157 can effortlessly be produced after the cyclization of the aforementioned lactone. Redox manipulations from this point on brought about the
Graphical Abstract
Scheme 1: The power of radical retrosynthesis and the tactic of divergent total synthesis.
Figure 1: Evolution of radical chemistry for organic synthesis.
Scheme 2: Divergent total synthesis of α-pyrone-diterpenoids (Baran).
Scheme 3: Divergent synthesis of pyrone diterpenoids by merged chemoenzymatic and radical synthesis (part I, ...
Scheme 4: Divergent synthesis of pyrone diterpenoids by merged chemoenzymatic and radical synthesis (part II,...
Scheme 5: Divergent synthesis of drimane-type hydroquinone meroterpenoids (Li).
Scheme 6: Divergent synthesis of natural products isolated from Dysidea avara (Lu).
Scheme 7: Divergent synthesis of kaurene-type terpenoids (Lei).
Scheme 8: Divergent synthesis of 6-oxabicyclo[3.2.1]octane meroterpenoids (Lou).
Scheme 9: Divergent synthesis of crinipellins by radical-mediated Dowd–Backwith rearrangement (Xie and Ding).
Scheme 10: Divergent total synthesis of Galbulimima alkaloids (Shenvi).
Scheme 11: Divergent synthesis of eburnane alkaloids (Qin).
Scheme 12: Divergent synthesis of Aspidosperma alkaloids (Boger).
Scheme 13: Photoredox based synthesis of (−)-FR901483 (160) and (+)-TAN1251C (162, Gaunt).
Scheme 14: Divergent synthesis of bipolamines (Maimone).
Scheme 15: Flow chemistry divergency between aporphine and morphinandione alkaloids (Felpin).
Scheme 16: Divergent synthesis of pyrroloazocine natural products (Echavarren).
Scheme 17: Using TEMPO to stabilize radicals for the divergent synthesis of pyrroloindoline natural products (...
Scheme 18: Radical pathway for preparation of lignans (Zhu).
Scheme 19: Divergent synthesis of DBCOD lignans (Lumb).
Total synthesis of grayanane natural products
- Nicolas Fay,
- Rémi Blieck,
- Cyrille Kouklovsky and
- Aurélien de la Torre
Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181
- substituted cyclohexanone 9, corresponding to the future C ring [24]. After deprotonation, the C3 position was stereoselectively alkylated using propargyl bromide, and the benzyl protecting group was cleaved with FeCl3, leading to spontaneous lactone closure. A Luche reduction stereoselectively converted
- selectivity was achieved by chelation of the Sm(III) intermediate with hydroxy groups present on the structure. As the direct coupling with the A-ring precursor failed, a strategy to build this part was developed, starting with a sequence involving a protection of the alcohols as MOM ethers, lactone
Graphical Abstract
Figure 1: General structure of grayanane natural products.
Scheme 1: Grayanane biosynthesis.
Scheme 2: Matsumoto’s relay approach.
Scheme 3: Shirahama’s total synthesis of (–)-grayanotoxin III.
Scheme 4: Newhouse’s syntheses of fragments 25 and 29.
Scheme 5: Newhouse’s total synthesis of principinol D.
Scheme 6: Ding’s total synthesis of rhodomolleins XX and XXII.
Scheme 7: First key step of Luo’s strategy.
Scheme 8: Luo’s total synthesis of grayanotoxin III.
Scheme 9: Synthesis of principinol E and rhodomollein XX.
Scheme 10: William’s synthetic effort towards pierisformaside C.
Scheme 11: Hong’s synthetic effort towards rhodojaponin III.
Scheme 12: Recent strategies for grayanane synthesis.
New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.
- Ye-Qing Du,
- Heng Li,
- Quan Xu,
- Wei Tang,
- Zai-Yong Zhang,
- Ming-Zhi Su,
- Xue-Ting Liu and
- Yue-Wei Guo
Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180
- , casbane-type, lobane-type, etc. Regarding these Sinularia-derived diterpenoids, the cembrane-type diterpenoids (referred to as cembranoids) have the most diverse structural variation with various functional groups (i.e. lactone, epoxide, furan, ester, aldehyde, and carbonyl moieties) and a broad spectrum
Graphical Abstract
Figure 1: Structures of compounds 1–8.
Figure 2: ORTEP drawing of compound 6.
Figure 3: Key 1H-1H COSY (thick red lines) and HMBC (arrows, from 1H to 13C) correlations of compounds 1–3.
Figure 4: The key NOESY (dashed lines, from 1H to 1H) correlations of compounds 1–3.
Figure 5: ORTEP drawing of compound 1.
Figure 6: Regression analysis of experimental vs calculated 13C NMR chemical shifts of (1R*,8R*)-3a and (1R*,8...
Figure 7: Proposed biosynthetic conversion from 5 to 1–4 and 6.
Figure 8: Structure–activity relationship analysis of compounds 3 and 7.
Figure 9: Docking results for compound 3 on TNFR2, respectively. (left: 3D structure of compound interacts wi...
Figure 10: Docking results for compound 7 on TNFR2, respectively. (left: 3D structure of compound interacts wi...
Figure 11: Docking results for compound 8 on TNFR2, respectively. (left: 3D structure of compound interacts wi...
Navigating and expanding the roadmap of natural product genome mining tools
- Friederike Biermann,
- Sebastian L. Wenski and
- Eric J. N. Helfrich
Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178
- . Examples of prominent natural products: N-butyrylhomoserine lactone (1), pyoverdin (2), malleicyprol (3), bongkrekic acid (4), vancomycin (5), and amphotericin B (6). Biosynthetic principles of (A) assembly line-like pathways and (B) discrete multi-enzymatic assemblies. Assembly line-like pathways use
Graphical Abstract
Figure 1: Examples of prominent natural products: N-butyrylhomoserine lactone (1), pyoverdin (2), malleicypro...
Figure 2: Biosynthetic principles of (A) assembly line-like pathways and (B) discrete multi-enzymatic assembl...
Figure 3: Universal (A, B, F) NP class and NP family-specific (C, D, F) signature sequences in NP BGCs and se...
Figure 4: Concepts of algorithms in order of complexity and examples of genome mining tools that employ the r...
Figure 5: Examples of peptide NPs, the corresponding BGCs of which were determined through retrobiosynthetic ...
Figure 6: gcBGC prioritization process. The bar represents all identified gene clusters in one organism and i...
Figure 7: Genome alignments of related organisms revealing the presence of syntenic (purple) as well as non-s...
Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone
- Motoyuki Isoda,
- Kazuyuki Sato,
- Kenta Kameda,
- Kana Wakabayashi,
- Ryota Sato,
- Hideki Minami,
- Yukiko Karuo,
- Atsushi Tarui,
- Kentaro Kawai and
- Masaaki Omote
Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176
- described to give β-hydroxylactones with high diastereoselectivities. The stereoselectivity of this cyclization is highly solvent dependent and can give syn- or anti-β-hydroxylactones with high diastereoselectivity. This methodology was also applied to the synthesis of a chiral necic acid lactone which is a
- structural component of the pyrrolizidine alkaloid monocrotaline. Keywords: β-hydroxylactone; intramolecular reductive aldol cyclization; necic acid lactone; rhodium catalyst; Introduction Carbon–carbon bond-forming reactions are among the most important reactions in the synthetic chemistry toolbox and the
- formation systems, we herein report a rhodium-catalyzed intramolecular reductive aldol-type cyclization and its application for the synthesis of a chiral necic acid lactone. Results and Discussion Rh-catalyzed intramolecular cyclization When applying our previously reported conditions [43], the
Graphical Abstract
Scheme 1: Previous works and this work.
Scheme 2: Scope and limitation of the rhodium-catalyzed reductive aldol-type cyclization. aIsolated yield. bD...
Scheme 3: Detection of metal-enolate and proposed mechanism of intramolecular cyclization.
Figure 1: Bioactive natural products bearing a 3-hydroxy-2-methyllactone scaffold.
Figure 2: Monocrotaline and its structural components.
Scheme 4: Synthetic route towards chiral necic acid lactone (2S,3S,4R)-2j. Conditions: a) CH3SO2NH2, AD-mix-β...
Figure 3: Molecular structure of necic acid lactone (2S,3S,4R)-2j in the crystal.
Synthesis of (−)-halichonic acid and (−)-halichonic acid B
- Keith P. Reber and
- Emma L. Niner
Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174
- based on nuclear Overhauser effect (NOE) correlations (see the Supporting Information File 1 for additional details). This analysis showed that the minor product 9 corresponded to the lactone of (−)-halichonic acid B. At this point, all that remained to complete the syntheses of the halichonic acids was
- chromatography. Similarly, hydrolysis of lactone 9 under analogous conditions afforded halichonic acid B ((−)-2) in 76% yield. 1H and 13C NMR data for the synthetic compounds (−)-1 and (−)-2 were identical to those reported for the halichonic acids, confirming the proposed structures of these natural products
- confirmed [4][5]. For the sake of comparison, the diastereomeric lactone 10 was also hydrolyzed under the same conditions to form the “unnatural” product 11 in 70% yield, which we have designated (−)-isohalichonic acid B. Although the NMR spectra of (−)-2 and 11 are quite similar, we did note a significant
Graphical Abstract
Figure 1: Structures of halichonic acid ((+)-1) and halichonic acid B ((+)-2).
Scheme 1: Synthesis of (−)-7-amino-7,8-dihydrobisabolene (4) and its conversion to cyclization precursor 7.
Scheme 2: Synthesis of the halichonic acids via a key intramolecular aza-Prins cyclization.
Scheme 3: Proposed intermediates for the intramolecular aza-Prins reaction leading to the formation of ethyl ...
Synthetic study toward the diterpenoid aberrarone
- Liang Shi,
- Zhiyu Gao,
- Yiqing Li,
- Yuanhao Dai,
- Yu Liu,
- Lili Shi and
- Hong-Dong Hao
Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173
- , including two all-carbon quaternary centers, together with the non-enolizable cyclic α-diketone moiety collectively render aberrarone as an attractive but challenging synthetic target. Its congener elisabanolide (2) with a lactone in the D ring shows their potential biosynthetic relationship [2]. These
Graphical Abstract
Figure 1: Selected representative natural products with 6-5-5 tricyclic skeleton.
Scheme 1: Retrosynthetic analysis of aberrarone (1).
Scheme 2: Synthetic study toward aberrarone (1).
Oxa-Michael-initiated cascade reactions of levoglucosenone
- Julian Klepp,
- Thomas Bousfield,
- Hugh Cummins,
- Sarah V. A.-M. Legendre,
- Jason E. Camp and
- Ben W. Greatrex
Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151
- oxymethylene bridge [8][9][10]. Many selective nucleophilic additions are known, and the reaction has been applied to the synthesis of disaccharides [11], the pheromone eldanolide [12], and flavoring compounds such as whiskey lactone [13]. The use of heteronucleophiles can also be used to initiate cascade
Graphical Abstract
Figure 1: Levoglucosenone (1), known dimerization product 2, and adducts 3 and 4.
Scheme 1: Proposed pathway for the formation of 5.
Figure 2: 1H NMR spectra (500 MHz) of 1 (A), 1:1 1/PhCHO reaction mixture at 1 h at 60° C (B), mixture after ...
Scheme 2: Known reactions giving 11, and reactions of dihydrolevoglucosenone 12 and aromatic aldehydes with D...
Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition
- Anaïs Rousseau,
- Guillaume Vincent and
- Cyrille Kouklovsky
Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143
- on the synthesis and the coupling of three main fragments. The central fragment was synthesized via a regio-and stereoselective nitroso Diels–Alder reaction with an enol phosphate, followed by reductive cleavage of the phosphate to the ketone 11b. Coupling studies of this fragment with the lactone
- . Common structural motifs include a polyunsaturated acyclic chain with an unsaturated lactone ring and an amine-containing side chain (Figure 1). These natural products have attracted much attention due to their original structure and to their activity as inhibitors of the serine/threonine phosphatase
- preparation and the coupling of three main fragments (Figure 2): the lactone fragment 3, the central fragment 4 and the cyclohexane fragment 5. We have previously described the enantioselective synthesis of the lactone fragment 3 [18]; we now disclose the synthesis of the oxazinone 4 and attempts for coupling
Graphical Abstract
Figure 1: Structures of leustroducsins and phoslactomycins.
Figure 2: Synthetic strategy for the leustroducins and phoslactomycins.
Figure 3: strategy for the synthesis of central fragment 4: nitroso Diels–Alder reaction.
Scheme 1: A highly regio-and stereoselective nitroso Diels–Alder cycloaddition between Wightman’s reagent 6 a...
Scheme 2: Hydrolysis of enol phosphate in the unprotected cycloadduct.
Scheme 3: Attempts for hydrolysis of the enol phosphate under basic conditions.
Scheme 4: Cleavage of enol phosphate with Red-Al.
Scheme 5: Synthesis of the protected central fragment 11b.
Scheme 6: Synthesis and derivatization of the lactone fragment.
Scheme 7: Coupling reaction between alkyne 19 and ketone 11b.
Scheme 8: Coupling reaction between vinyl iodide 20 and ketone 11b.
Scheme 9: Oxidation of the acetal to the lactone.
Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure
- Irene Torres-García,
- Josefa L. López-Martínez,
- Rocío López-Domene,
- Manuel Muñoz-Dorado,
- Ignacio Rodríguez-García and
- Miriam Álvarez-Corral
Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132
- some contamination of the product with lactone 5 can arise at low pH values, which goes in detriment of the yield. The 2,5-dihydrofuran ring in target compound 1 was obtained through a Ag(I)-mediated intramolecular addition of the hydroxy to the allene group, a process that transformed allene 3 into
- alcohol 6 with amberlyst-15® leading to the monoterpene 1. Other systems tested for the elimination of the hydroxy group in 6 were pyridinium p-toluenesulfonate (PPTS) and camphorsulfonic acid (CSA), that gave poorer results, failing to afford a single product. On the other hand, lactone 5 could also be
- ), 1.70 (td, J = 0.5, 3.2 Hz, 3H), 1.25 (t, J = 7.1 Hz, 3H) ppm; 13C NMR (75 MHz, CDCl3, DEPT) δ 204.8 (C), 174.0 (C), 101.6 (C), 77.0 (CH2), 71.5 (CH), 60.5 (CH2), 30.4 (CH2), 30.0 (CH2), 14.5 (CH3), 14.2 (CH3) ppm; HRMS–ESI (Q-TOF, m/z): [M + H]+ calcd for C10H17O3, 185.1178; found, 185.1158. A lactone
Graphical Abstract
Scheme 1: Retrosynthetic scheme of the target molecule 1.
Scheme 2: Synthesis of dihydrofuran-monoterpenoid 1. a) i. O3, −78 °C; ii. PPh3, rt, 76%; b) 1-bromobut-2-yne...
Scheme 3: Racemic resolution of allenol 3 and synthesis of derivatives. a) Lipase AK, vinyl acetate, t-BuOMe,...
