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Search for "lactone" in Full Text gives 255 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis
- Shahboz Yakubov and
- Joshua P. Barham
Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183
- (+)-sclareolide (C2 and C3) are remote from the lactone EWG and both form secondary radicals. Thus, the fluorination of these positions is presumably dictated by hindrance, given that the C3 position is neighbored by a gem-dimethyl group and is fluorinated to a lesser extent (22%). In both reports, the C2/C3
Graphical Abstract
Figure 1: Fluorine-containing drugs.
Figure 2: Fluorinated agrochemicals.
Scheme 1: Selectivity of fluorination reactions.
Scheme 2: Different mechanisms of photocatalytic activation. Sub = substrate.
Figure 3: Jablonski diagram showing visible-light-induced energy transfer pathways: a) absorption, b) IC, c) ...
Figure 4: Schematic illustration of TTET.
Figure 5: Organic triplet PSCats.
Figure 6: Additional organic triplet PSCats.
Figure 7: A) Further organic triplet PSCats and B) transition metal triplet PSCats.
Figure 8: Different fluorination reagents grouped by generation.
Scheme 3: Synthesis of Selectfluor®.
Scheme 4: General mechanism of PS TTET C(sp3)–H fluorination.
Scheme 5: Selective benzylic mono- and difluorination using 9-fluorenone and xanthone PSCats, respectively.
Scheme 6: Chen’s photosensitized monofluorination: reaction scope.
Scheme 7: Chen’s photosensitized benzylic difluorination reaction scope.
Scheme 8: Photosensitized monofluorination of ethylbenzene on a gram scale.
Scheme 9: Substrate scope of Tan’s AQN-photosensitized C(sp3)–H fluorination.
Scheme 10: AQN-photosensitized C–H fluorination reaction on a gram scale.
Scheme 11: Reaction mechanism of the AQN-assisted fluorination.
Figure 9: 3D structures of the singlet ground and triplet excited states of Selectfluor®.
Scheme 12: Associated transitions for the activation of acetophenone by violet light.
Scheme 13: Ethylbenzene C–H fluorination with various PSCats and conditions.
Scheme 14: Effect of different PSCats on the C(sp3)–H fluorination of cyclohexane (39).
Scheme 15: Reaction scope of Chen’s acetophenone-photosensitized C(sp3)–H fluorination reaction.
Figure 10: a) Site-selectivity of Chen’s acetophenone-photosensitized C–H fluorination reaction [201]. b) Site-sele...
Scheme 16: Formation of the AQN–Selectfluor® exciplex Int1.
Scheme 17: Generation of the C3 2° pentane radical and the Selectfluor® N-radical cation from the exciplex.
Scheme 18: Hydrogen atom abstraction by the Selectfluor® N-radical cation from pentane to give the C3 2° penta...
Scheme 19: Fluorine atom transfer from Selectfluor® to the C3 2° pentane radical to yield 3-fluoropentane and ...
Scheme 20: Barrierless fluorine atom transfer from Int1 to the C3 2° pentane radical to yield 3-fluoropentane,...
Scheme 21: Ketone-directed C(sp3)–H fluorination.
Scheme 22: Ketone-directed fluorination through a 5- and a 6-membered transition state, respectively.
Scheme 23: Effect of different PSCats on the photosensitized C(sp3)–H fluorination of 47.
Scheme 24: Substrate scope of benzil-photoassisted C(sp3)–H fluorinations.
Scheme 25: A) Benzil-photoassisted enone-directed C(sp3)–H fluorination. B) Classification of the reaction mod...
Scheme 26: A) Xanthone-photoassisted ketal-directed C(sp3)–H fluorination. B) Substrate scope. C) C–H fluorina...
Scheme 27: Rationale for the selective HAT at the C2 C–H bond of galactose acetonide.
Scheme 28: Photosensitized C(sp3)–H benzylic fluorination of a peptide using different PSCats.
Scheme 29: Peptide scope of 5-benzosuberenone-photoassisted C(sp3)–H fluorinations.
Scheme 30: Continuous flow PS TTET monofluorination of 72.
Scheme 31: Photosensitized C–H fluorination of N-butylphthalimide as a PSX.
Scheme 32: Substrate scope and limitations of the PSX C(sp3)–H monofluorination.
Scheme 33: Substrate crossover monofluorination experiment.
Scheme 34: PS TTET mechanism proposed by Hamashima and co-workers.
Scheme 35: Photosensitized TFM of 78 to afford α-trifluoromethylated ketone 80.
Scheme 36: Substrate scope for photosensitized styrene TFM to give α-trifluoromethylated ketones.
Scheme 37: Control reactions for photosensitized TFM of styrenes.
Scheme 38: Reaction mechanism for photosensitized TFM of styrenes to afford α-trifluoromethylated ketones.
Scheme 39: Reaction conditions for TFMs to yield the cis- and the trans-product, respectively.
Scheme 40: Substrate scope of trifluoromethylated (E)-styrenes.
Scheme 41: Strategies toward trifluoromethylated (Z)-styrenes.
Scheme 42: Substrate scope of trifluoromethylated (Z)-styrenes.
Scheme 43: Reaction mechanism for photosensitized TFM of styrenes to afford E- or Z-products.
Syntheses of spliceostatins and thailanstatins: a review
- William A. Donaldson
Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166
- hydrogenation over Pt2O and then low-temperature DIBAL reduction afforded the all-cis tetrasubstituted tetrahydropyran 27. In Koide et al.’s synthesis, the unsaturated lactone 29 was prepared via the Wittig methenylation of 24, followed by aminal hydrolysis, methallylation of the 2° alcohol 28, and ring-closing
Graphical Abstract
Figure 1: Structures of spliceostatins/thailanstatins.
Scheme 1: Synthetic routes to protected (2Z,4S)-4-hydroxy-2-butenoic acid fragments.
Scheme 2: Kitahara synthesis of the (all-cis)-2,3,5,6-tetrasubstituted tetrahydropyran.
Scheme 3: Koide synthesis of (all-cis)-2,3,5,6-tetrasubstituted tetrahydropyran.
Scheme 4: Nicolaou synthesis of the (all-cis)-2,3,5,6-tetrasubstituted tetrahydropyran.
Scheme 5: Jacobsen synthesis of the (all-cis)-2,3,5,6-tetrasubstituted tetrahydropyran.
Scheme 6: Unproductive attempt to generate the (all-cis)-tetrahydropyranone 50.
Scheme 7: Ghosh synthesis of the C-7–C-14 (all-cis)-tetrahydropyran segment.
Scheme 8: Ghosh’s alternative route to the (all-cis)-tetrahydropyranone 50.
Scheme 9: Alternative synthesis of the dihydro-3-pyrone 58.
Scheme 10: Kitahara’s 1st-generation synthesis of the C-1–C-6 fragment of FR901464 (1).
Scheme 11: Kitahara 1st-generation synthesis of the C-1–C-6 fragment of FR901464 (1).
Scheme 12: Nimura/Arisawa synthesis of the C-1-phenyl segment.
Scheme 13: Ghosh synthesis of the C-1–C-6 fragment of FR901464 (1) from (R)-glyceraldehyde acetonide.
Scheme 14: Jacobsen synthesis of the C-1–C-7 segment of FR901464 (1).
Scheme 15: Koide synthesis of the C-1–C-7 segment of FR901464 (1).
Scheme 16: Ghosh synthesis of the C-1–C-5 segment 102 of thailanstatin A (7).
Scheme 17: Nicolaou synthesis of the C-1–C-9 segments of spliceostatin D (9) and thailanstatins A (7) and B (5...
Scheme 18: Ghosh synthesis of the C-1–C-6 segment 115 of spliceostatin E (10).
Scheme 19: Fragment coupling via Wittig and modified Julia olefinations by Kitahara.
Scheme 20: Fragment coupling via cross-metathesis by Koide.
Scheme 21: The Ghosh synthesis of spliceostatin A (4), FR901464 (1), spliceostatin E (10), and thailanstatin m...
Scheme 22: Arisawa synthesis of a C-1-phenyl analog of FR901464 (1).
Scheme 23: Jacobsen fragment coupling by a Pd-catalyzed Negishi coupling.
Scheme 24: Nicolaou syntheses of thailanstatin A and B (7 and 5) and spliceostatin D (9) via a Pd-catalyzed Su...
Scheme 25: The Ghosh synthesis of spliceostatin G (11) via Suzuki–Miyaura coupling.
Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions
- Clément Q. Fontenelle,
- Thibault Thierry,
- Romain Laporte,
- Emmanuel Pfund and
- Thierry Lequeux
Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160
- the corresponding acetate (4%, not shown), the bromomethyllactone 15 (8%), and alkene Z-13 (1%). Only lactone 14 could be isolated in a pure form (58% yield). The amount of HBr/AcOH had little influence on the selectivity (Table 4, entry 2) of the reaction. However, in the presence of TBAB (2.5 equiv
- ) and CSA (2 equiv) an 84% conversion into mainly brominated lactone 15 (79%) with traces of hydroxylated lactone 14, and of bromoalkene Z-13 was determined by crude 19F NMR. The remaining 8% appeared to be the β-chloromethyllactone 19 (see Scheme 7 below), an analogue of 15 as determined by NMR
- ). The former, using an excess of acid (33% HBr in AcOH solution) favored the direct nucleophilic attack (path b) leading to lactone 14, whereas the latter in the presence of TBAB/CSA allowed bromide addition on the same side of the fluorine atom (path a) leading to lactone 15 [31]. However, the reaction
Graphical Abstract
Figure 1: Representative fluorinated nucleos(t)ides and acyclonucleotides.
Figure 2: Acyclonucleotides as nucleotide surrogates.
Figure 3: Olefination approaches and ring-opening of oxetane derivatives.
Scheme 1: Preparation of fluoroakylidene-oxetanes and their ring-opening reactions.
Scheme 2: Synthesis of benzyloxy-substituted fluoroethylidene-oxetane derivative 8.
Scheme 3: Effect of the medium on the selective formation of derivative 10.
Scheme 4: Mechanism for the formation of dihydrofuran 10.
Scheme 5: Mechanism for the formation of unsaturated lactones 14 and 15.
Scheme 6: Opening reaction of ethyl 2-(oxetanyl-3-idene)acetate (16).
Scheme 7: Functionalization of bromomethyllactone 15 and its analogues.
Scheme 8: Functionalization by substitution reaction of the bromide E-1d vs ring-opening reaction of the oxet...
Scheme 9: Preparation of tetrasubstituted fluoroalkenes.
When metal-catalyzed C–H functionalization meets visible-light photocatalysis
- Lucas Guillemard and
- Joanna Wencel-Delord
Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147
Graphical Abstract
Figure 1: Concept of dual synergistic catalysis.
Figure 2: Classification of catalytic systems involving two catalysts.
Figure 3: General mechanism for the dual nickel/photoredox catalytic system.
Figure 4: General mechanisms for C–H activation catalysis involving different reoxidation strategies.
Figure 5: Indole synthesis via dual C–H activation/photoredox catalysis.
Figure 6: Proposed mechanism for the indole synthesis via dual catalysis.
Figure 7: Oxidative Heck reaction on arenes via the dual catalysis.
Figure 8: Proposed mechanism for the Heck reaction on arenes via dual catalysis.
Figure 9: Oxidative Heck reaction on phenols via the dual catalysis.
Figure 10: Proposed mechanism for the Heck reaction on phenols via dual catalysis.
Figure 11: Carbazole synthesis via dual C–H activation/photoredox catalysis.
Figure 12: Proposed mechanism for the carbazole synthesis via dual catalysis.
Figure 13: Carbonylation of enamides via the dual C–H activation/photoredox catalysis.
Figure 14: Proposed mechanism for carbonylation of enamides via dual catalysis.
Figure 15: Annulation of benzamides via the dual C–H activation/photoredox catalysis.
Figure 16: Proposed mechanism for the annulation of benzamides via dual catalysis.
Figure 17: Synthesis of indoles via the dual C–H activation/photoredox catalysis.
Figure 18: Proposed mechanism for the indole synthesis via dual catalysis.
Figure 19: General concept of dual catalysis merging C–H activation and photoredox catalysis.
Figure 20: The first example of dual catalysis merging C–H activation and photoredox catalysis.
Figure 21: Proposed mechanism for the C–H arylation with diazonium salts via dual catalysis.
Figure 22: Dual catalysis merging C–H activation/photoredox using diaryliodonium salts.
Figure 23: Direct arylation via the dual catalytic system reported by Xu.
Figure 24: Direct arylation via dual catalytic system reported by Balaraman.
Figure 25: Direct arylation via dual catalytic system reported by Guo.
Figure 26: C(sp3)–H bond arylation via the dual Pd/photoredox catalytic system.
Figure 27: Acetanilide derivatives acylation via the dual C–H activation/photoredox catalysis.
Figure 28: Proposed mechanism for the C–H acylation with α-ketoacids via dual catalysis.
Figure 29: Acylation of azobenzenes via the dual catalysis C–H activation/photoredox.
Figure 30: C2-acylation of indoles via the dual C–H activation/photoredox catalysis.
Figure 31: Proposed mechanism for the C2-acylation of indoles with aldehydes via dual catalysis.
Figure 32: C2-acylation of indoles via the dual C–H activation/photoredox catalysis.
Figure 33: Perfluoroalkylation of arenes via the dual C–H activation/photoredox catalysis.
Figure 34: Proposed mechanism for perfluoroalkylation of arenes via dual catalysis.
Figure 35: Sulfonylation of 1-naphthylamides via the dual C–H activation/photoredox catalysis.
Figure 36: Proposed mechanism for sulfonylation of 1-naphthylamides via dual catalysis.
Figure 37: meta-C–H Alkylation of arenes via visible-light metallaphotocatalysis.
Figure 38: Alternative procedure for meta-C–H alkylation of arenes via metallaphotocatalysis.
Figure 39: Proposed mechanism for meta-C–H alkylation of arenes via metallaphotocatalysis.
Figure 40: C–H borylation of arenes via visible-light metallaphotocatalysis.
Figure 41: Proposed mechanism for C–H borylation of arenes via visible-light metallaphotocatalysis.
Figure 42: Undirected C–H aryl–aryl cross coupling via dual gold/photoredox catalysis.
Figure 43: Proposed mechanism for the undirected C–H aryl–aryl cross-coupling via dual catalysis.
Figure 44: Undirected C–H arylation of (hetero)arenes via dual manganese/photoredox catalysis.
Figure 45: Proposed mechanism for the undirected arylation of (hetero)arenes via dual catalysis.
Figure 46: Photoinduced C–H arylation of azoles via copper catalysis.
Figure 47: Photo-induced C–H chalcogenation of azoles via copper catalysis.
Figure 48: Decarboxylative C–H adamantylation of azoles via dual cobalt/photoredox catalysis.
Figure 49: Proposed mechanism for the C–H adamantylation of azoles via dual catalysis.
Figure 50: General mechanisms for the “classical” (left) and Cu-free variant (right) Sonogoshira reaction.
Figure 51: First example of a dual palladium/photoredox catalysis for Sonogashira-type couplings.
Figure 52: Arylation of terminal alkynes with diazonium salts via dual gold/photoredox catalysis.
Figure 53: Proposed mechanism for the arylation of terminal alkynes via dual catalysis.
Figure 54: C–H Alkylation of alcohols promoted by H-atom transfer (HAT).
Figure 55: Proposed mechanism for the C–H alkylation of alcohols promoted by HAT.
Figure 56: C(sp3)–H arylation of latent nucleophiles promoted by H-atom transfer.
Figure 57: Proposed mechanism for the C(sp3)–H arylation of latent nucleophiles promoted by HAT.
Figure 58: Direct α-arylation of alcohols promoted by H-atom transfer.
Figure 59: Proposed mechanism for the direct α-arylation of alcohols promoted by HAT.
Figure 60: C–H arylation of amines via dual Ni/photoredox catalysis.
Figure 61: Proposed mechanism for the C–H arylation of amines via dual Ni/photoredox catalysis.
Figure 62: C–H functionalization of nucleophiles via excited ketone/nickel dual catalysis.
Figure 63: Proposed mechanism for the C–H functionalization enabled by excited ketones.
Figure 64: Selective sp3–sp3 cross-coupling promoted by H-atom transfer.
Figure 65: Proposed mechanism for the selective sp3–sp3 cross-coupling promoted by HAT.
Figure 66: Direct C(sp3)–H acylation of amines via dual Ni/photoredox catalysis.
Figure 67: Proposed mechanism for the C–H acylation of amines via dual Ni/photoredox catalysis.
Figure 68: C–H hydroalkylation of internal alkynes via dual Ni/photoredox catalysis.
Figure 69: Proposed mechanism for the C–H hydroalkylation of internal alkynes.
Figure 70: Alternative procedure for the C–H hydroalkylation of ynones, ynoates, and ynamides.
Figure 71: Allylic C(sp3)–H activation via dual Ni/photoredox catalysis.
Figure 72: Proposed mechanism for the allylic C(sp3)–H activation via dual Ni/photoredox catalysis.
Figure 73: Asymmetric allylation of aldehydes via dual Cr/photoredox catalysis.
Figure 74: Proposed mechanism for the asymmetric allylation of aldehydes via dual catalysis.
Figure 75: Aldehyde C–H functionalization promoted by H-atom transfer.
Figure 76: Proposed mechanism for the C–H functionalization of aldehydes promoted by HAT.
Figure 77: Direct C–H arylation of strong aliphatic bonds promoted by HAT.
Figure 78: Proposed mechanism for the C–H arylation of strong aliphatic bonds promoted by HAT.
Figure 79: Direct C–H trifluoromethylation of strong aliphatic bonds promoted by HAT.
Figure 80: Proposed mechanism for the C–H trifluoromethylation of strong aliphatic bonds.
Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization
- Dominik Göbel,
- Marius Friedrich,
- Enno Lork and
- Boris J. Nachtsheim
Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139
- reduction with NaBH4 to give the primary alcohol 19. In contrast to benzaldehyde 7, carbaldehyde 18 showed no decomposition at ambient temperature. While acidic hydrolysis of 19 provided exocyclic γ-lactone 20, the substitution reaction with DPPA/NaN3 yielded the primary azide in 87% yield. In accordance to
Graphical Abstract
Scheme 1: a) Schematic depiction of the Jablonski diagram. b) Schematic representation of El-Sayed’s rule.
Figure 1: Top: literature examples of organic compounds showing RTP in the crystalline state (a) and in solut...
Scheme 2: Reaction conditions for para-bromobenzaldehyde 3: a) 1) 2-amino-2-methylpropan-1-ol, 4 Å MS, CH2Cl2...
Scheme 3: Reaction conditions: a) Br2, Fe powder, CHCl3, 0 °C, 4 h, 99%; b) KOH, KI, MeI, DMSO, 25 °C, 18 h, ...
Scheme 4: Reaction conditions: a) 1) NaH, THF, 0 °C, 30 min; 2) MeI, THF, 0 °C to 25 °C, 2 h, 99%; b) 1) MeOT...
Scheme 5: a) CuAAC reactions of azide-functionalized bromocarbaldehydes 3, 4 and 5 with terminal alkynes to t...
Figure 2: a) Normalized UV–vis absorption spectra of 3 (blue line), 34 (olive line), 4 (green line) and 38 (r...
Figure 3: a) Normalized UV–vis absorption spectra of 5 (blue line), 16 (green line), 42 (olive line) and 45 (...
NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides
- Alyn T. Davies,
- Mark D. Greenhalgh,
- Alexandra M. Z. Slawin and
- Andrew D. Smith
Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129
- -substituted β-lactone products in a high yield, diastereo-, and enantioselectivity (Figure 2A) [46]. Chi and co-workers have reported limited examples of oxidative [2 + 2] cycloadditions using hydrocinnamaldehyde as an azolium enolate precursor and the NHC precatalyst 2, giving β-lactone products in high
- -aroyloxyaldehyde 4 and trifluoromethylacetophenone (5) as reactants began using the NHC precatalyst 3, triethylamine as the base, and THF as the solvent (Table 1, entry 1). A moderate conversion (48%, as determined by NMR analysis) to the desired β-lactone product 6 as a 70:30 mixture of diastereoisomers was
- , diethyl ether, and toluene showed no improvement upon the yield obtained with THF (Table 1, entries 4–6). Unfortunately, attempts to isolate the desired β-lactone product 6 were unsuccessful, with 6 being unstable to chromatographic purification under a variety of different conditions. As such, following
Graphical Abstract
Figure 1: Organocatalytic enantioselective aldol approaches using trifluoroacetophenone derivatives.
Figure 2: NHC-catalyzed approaches to β-lactones using trifluoroacetophenone derivatives.
Scheme 1: Reaction scope with respect to the nucleophile. aIsolated yield of the product in >95:5 dr. bDeterm...
Scheme 2: Reaction scope with respect to the trifluoroacetophenone derivative and α-aroyloxyaldehyde. aIsolat...
Scheme 3: Proposed mechanism.
Heterogeneous photocatalysis in flow chemical reactors
- Christopher G. Thomson,
- Ai-Lan Lee and
- Filipe Vilela
Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125
Graphical Abstract
Figure 1: A) Bar chart of the publications per year for the topics “Photocatalysis” (49,662 instances) and “P...
Figure 2: A) Professor Giacomo Ciamician and Dr. Paolo Silber on their roof laboratory at the University of B...
Scheme 1: PRC trifluoromethylation of N-methylpyrrole (1) using hazardous gaseous CF3I safely in a flow react...
Figure 3: A) Unit cells of the three most common crystal structures of TiO2: rutile, brookite, and anatase. R...
Figure 4: Illustration of the key semiconductor photocatalysis events: 1) A photon with a frequency exceeding...
Figure 5: Photocatalytic splitting of water by oxygen vacancies on a TiO2(110) surface. Reprinted with permis...
Figure 6: Proposed adsorption modes of A) benzene, B) chlorobenzene, C) toluene, D) phenol, E) anisole, and F...
Figure 7: Structures of the sulfonate-containing organic dyes RB5 (3) and MX-5B (4) and the adsorption isothe...
Figure 8: Idealised triclinic unit cell of a g-C3N4 type polymer, displaying possible hopping transport scena...
Figure 9: Idealised structure of a perfect g-C3N4 sheet. The central unit highlighted in red represents one t...
Figure 10: Timeline of the key processes of charge transport following the photoexcitation of g-C3N4, leading ...
Scheme 2: Photocatalytic bifunctionalisation of heteroarenes using mpg-C3N4, with the selected examples 5 and ...
Figure 11: A) Structure of four linear conjugated polymer photocatalysts for hydrogen evolution, displaying th...
Figure 12: Graphical representation of the common methods used to immobilise molecular photocatalysts (PC) ont...
Figure 13: Wireless light emitter-supported TiO2 (TiO2@WLE) HPCat spheres powered by resonant inductive coupli...
Figure 14: Graphical representation of zinc–perylene diimide (Zn-PDI) supramolecular assembly photocatalysis v...
Scheme 3: Upconversion of NIR photons to the UV frequency by NaYF4:Yb,Tm nanocrystals sequentially coated wit...
Figure 15: Types of reactors employed in heterogeneous photocatalysis in flow. A) Fixed bed reactors and the s...
Figure 16: Electrochemical potential of common semiconductor, transition metal, and organic dye-based photocat...
Scheme 4: Possible mechanisms of an immobilised molecular photoredox catalyst by oxidative or reductive quenc...
Scheme 5: Scheme of the CMB-C3N4 photocatalytic decarboxylative fluorination of aryloxyacetic acids, with the...
Scheme 6: Scheme of the g-C3N4 photocatalytic desilylative coupling reaction in flow and proposed mechanism [208].
Scheme 7: Proposed mechanism of the radical cyclisation of unsaturated alkyl 2-bromo-1,3-dicarbonyl compounds...
Scheme 8: N-alkylation of benzylamine and schematic of the TiO2-coated microfluidic device [213].
Scheme 9: Proposed mechanism of the Pt@TiO2 photocatalytic deaminitive cyclisation of ʟ-lysine (23) to ʟ-pipe...
Scheme 10: A) Proposed mechanism for the photocatalytic oxidation of phenylboronic acid (24). B) Photos and SE...
Scheme 11: Proposed mechanism for the DA-CMP3 photocatalytic aza-Henry reaction performed in a continuous flow...
Scheme 12: Proposed mechanism for the formation of the cyclic product 32 by TiO2-NC HPCats in a slurry flow re...
Scheme 13: Reaction scheme for the photocatalytic synthesis of homo and hetero disulfides in flow and scope of...
Scheme 14: Reaction scheme for the MoOx/TiO2 HPCat oxidation of cyclohexane (34) to benzene. The graph shows t...
Scheme 15: Proposed mechanism of the TiO2 HPC heteroarene C–H functionalisation via aryl radicals generated fr...
Scheme 16: Scheme of the oxidative coupling of benzylamines with the HOTT-HATN HPCat and selected examples of ...
Scheme 17: Photocatalysis oxidation of benzyl alcohol (40) to benzaldehyde (41) in a microflow reactor coated ...
Figure 17: Mechanisms of Dexter and Forster energy transfer.
Scheme 18: Continuous flow process for the isomerisation of alkenes with an ionic liquid-immobilised photocata...
Scheme 19: Singlet oxygen synthetic step in the total synthesis of canataxpropellane [265].
Scheme 20: Scheme and proposed mechanism of the singlet oxygen photosensitisation by CMP_X HPCats, with the st...
Scheme 21: Structures of CMP HPCat materials applied by Vilela and co-workers for the singlet oxygen photosens...
Scheme 22: Polyvinylchloride resin-supported TDCPP photosensitisers applied for singlet oxygen photosensitisat...
Scheme 23: Structure of the ionically immobilised TPP photosensitiser on amberlyst-15 ion exchange resins (TPP...
Scheme 24: Photosensitised singlet oxygen oxidation of citronellol (46) in scCO2, with automatic phase separat...
Scheme 25: Schematic of PS-Est-BDP-Cl2 being applied for singlet oxygen photosensitisation in flow. A) Pseudo-...
Scheme 26: Reaction scheme of the singlet oxygen oxidation of furoic acid (54) using a 3D-printed microfluidic...
Figure 18: A) Photocatalytic bactericidal mechanism by ROS oxidative cleavage of membrane lipids (R = H, amino...
Figure 19: A) Suggested mechanisms for the aqueous pollutant degradation by TiO2 in a slurry flow reactor [284-287]. B)...
Figure 20: Schematic of the flow system used for the degradation of aqueous oxytetracycline (56) solutions [215]. M...
Scheme 27: Degradation of a salicylic acid (57) solution by a coupled solar photoelectro-Fenton (SPEF) process...
Figure 21: A) Schematic flow diagram using the TiO2-coated NETmix microfluidic device for an efficient mass tr...
Recent synthesis of thietanes
- Jiaxi Xu
Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116
Graphical Abstract
Figure 1: Examples of biologically active thietane-containing molecules.
Figure 2: The diverse methods for the synthesis of thietanes.
Scheme 1: Synthesis of 1-(thietan-2-yl)ethan-1-ol (10) from 3,5-dichloropentan-2-ol (9).
Scheme 2: Synthesis of thietanose nucleosides 2,14 from 2,2-bis(bromomethyl)propane-1,3-diol (11).
Scheme 3: Synthesis of methyl 3-vinylthietane-3-carboxylate (19).
Scheme 4: Synthesis of 1,6-thiazaspiro[3.3]heptane (24).
Scheme 5: Synthesis of 6-amino-2-thiaspiro[3.3]heptane hydrochloride (28).
Scheme 6: Synthesis of optically active thietane 31 from vitamin C.
Scheme 7: Synthesis of an optically active thietane nucleoside from diethyl L-tartrate (32).
Scheme 8: Synthesis of thietane-containing spironucleoside 40 from 5-aldo-3-O-benzyl-1,2-O-isopropylidene-α-D...
Scheme 9: Synthesis of optically active 2-methylthietane-containing spironucleoside 43.
Scheme 10: Synthesis of a double-linked thietane-containing spironucleoside 48.
Scheme 11: Synthesis of two diastereomeric thietanose nucleosides via 2,4-di(benzyloxymethyl)thietane (49).
Scheme 12: Synthesis of the thietane-containing PI3k inhibitor candidate 54.
Scheme 13: Synthesis of the spirothietane 57 as the key intermediate to Nuphar sesquiterpene thioalkaloids.
Scheme 14: Synthesis of spirothietane 61 through a direct cyclic thioetherification of 3-mercaptopropan-1-ol.
Scheme 15: Synthesis of thietanes 66 from 1,3-diols 62.
Scheme 16: Synthesis of thietanylbenzimidazolone 75 from (iodomethyl)thiazolobenzimidazole 70.
Scheme 17: Synthesis of 2-oxa-6-thiaspiro[3.3]heptane (80) from bis(chloromethyl)oxetane 76 and thiourea.
Scheme 18: Synthesis of the thietane-containing glycoside, 2-O-p-toluenesulfonyl-4,6-thioanhydro-α-D-gulopyran...
Scheme 19: Synthesis of methyl 4,6-thioanhydro-α-D-glucopyranoside (89).
Scheme 20: Synthesis of thietane-fused α-D-galactopyranoside 93.
Scheme 21: Synthesis of thietane-fused α-D-gulopyranoside 100.
Scheme 22: Synthesis of 3,5-anhydro-3-thiopentofuranosides 104.
Scheme 23: Synthesis of anhydro-thiohexofuranosides 110, 112 and 113 from from 1,2:4,5-di-O-isopropylidene D-f...
Scheme 24: Synthesis of optically active thietanose nucleosides from D- and L-xyloses.
Scheme 25: Synthesis of thietane-fused nucleosides.
Scheme 26: Synthesis of 3,5-anhydro-3-thiopentofuranosides.
Scheme 27: Synthesis of 2-amino-3,5-anhydro-3-thiofuranoside 141.
Scheme 28: Synthesis of thietane-3-ols 145 from (1-chloromethyl)oxiranes 142 and hydrogen sulfide.
Scheme 29: Synthesis of thietane-3-ol 145a from chloromethyloxirane (142a).
Scheme 30: Synthesis of thietane-3-ols 145 from 2-(1-haloalkyl)oxiranes 142 and 147 with ammonium monothiocarb...
Scheme 31: Synthesis of 7-deoxy-5(20)thiapaclitaxel 154a, a thietane derivative of taxoids.
Scheme 32: Synthesis of 5(20)-thiadocetaxel 158 from 10-deacetylbaccatin III (155).
Scheme 33: Synthesis of thietane derivatives 162 as precursors for deoxythiataxoid synthesis through oxiraneme...
Scheme 34: Synthesis of 7-deoxy 5(20)-thiadocetaxel 154b.
Scheme 35: Mechanism for the formation of the thietane ring in 171 from oxiranes with vicinal leaving groups 1...
Scheme 36: Synthesis of cis-2,3-disubstituted thietane 175 from thiirane-2-methanol 172.
Scheme 37: Synthesis of a bridged thietane 183 from aziridine cyclohexyl tosylate 179 and ammonium tetrathiomo...
Scheme 38: Synthesis of thietanes via the photochemical [2 + 2] cycloaddition of thiobenzophenone 184a with va...
Scheme 39: Synthesis of spirothietanes through the photo [2 + 2] cycloaddition of cyclic thiocarbonyls with ol...
Scheme 40: Photochemical synthesis of spirothietane-thioxanthenes 210 from thioxanthenethione (208) and butatr...
Scheme 41: Synthesis of thietanes 213 from 2,4,6-tri(tert-butyl)thiobenzaldehyde (211) with substituted allene...
Scheme 42: Photochemical synthesis of spirothietanes 216 and 217 from N-methylthiophthalimide (214) with olefi...
Scheme 43: Synthesis of fused thietanes from quadricyclane with thiocarbonyl derivatives 219.
Scheme 44: Synthesis of tricyclic thietanes via the photo [2 + 2] cycloaddition of N-methyldithiosuccinimides ...
Scheme 45: Synthesis of tricyclic thietanes via the photo [2 + 2] cycloaddition of N-methylthiosuccinimide/thi...
Scheme 46: Synthesis of tricyclic thietanes via the photo [2 + 2] cycloaddition of N-alkylmonothiophthalimides...
Scheme 47: Synthesis of spirothietanes from dithiosuccinimides 223 with 2,3-dimethyl-2-butene (215a).
Scheme 48: Synthesis of thietanes 248a,b from diaryl thione 184b and ketene acetals 247a,b.
Scheme 49: Photocycloadditions of acridine-9-thiones 249 and pyridine-4(1H)-thione (250) with 2-methylacrynitr...
Scheme 50: Synthesis of thietanes via the photo [2 + 2] cycloaddition of mono-, di-, and trithiobarbiturates 2...
Scheme 51: Synthesis of spirothietanes via the photo [2 + 2] cycloaddition of 1,1,3-trimethyl-2-thioxo-1,2-dih...
Scheme 52: Synthesis of spirothietanes via the photo [2 + 2] cycloaddition of thiocoumarin 286 with olefins.
Scheme 53: Photochemical synthesis of thietanes 296–299 from semicyclic and acyclic thioimides 292–295 and 2,3...
Scheme 54: Photochemical synthesis of spirothietane 301 from 1,3,3-trimethylindoline-2-thione (300) and isobut...
Scheme 55: Synthesis of spirobenzoxazolethietanes 303 via the photo [2 + 2] cycloaddition of alkyl and aryl 2-...
Scheme 56: Synthesis of spirothietanes from tetrahydrothioxoisoquinolines 306 and 307 with olefins.
Scheme 57: Synthesis of spirothietanes from 1,3-dihydroisobenzofuran-1-thiones 311 and benzothiophene-1-thione...
Scheme 58: Synthesis of 2-triphenylsilylthietanes from phenyl triphenylsilyl thioketone (316) with electron-po...
Scheme 59: Diastereoselective synthesis of spiropyrrolidinonethietanes 320 via the photo [2 + 2] cycloaddition...
Scheme 60: Synthesis of bicyclic thietane 323 via the photo [2 + 2] cycloaddition of 2,4-dioxo-3,4-dihydropyri...
Scheme 61: Photo-induced synthesis of fused thietane-2-thiones 325 and 326 from silacyclopentadiene 324 and ca...
Scheme 62: Synthesis of highly strained tricyclic thietanes 328 via the intramolecular photo [2 + 2] cycloaddi...
Scheme 63: Synthesis of tri- and pentacyclic thietanes 330 and 332, respectively, through the intramolecular p...
Scheme 64: Synthesis of tricyclic thietanes 334 via the intramolecular photo [2 + 2] cycloaddition of N-vinylt...
Scheme 65: Synthesis of tricyclic thietanes 336 via the intramolecular photo [2 + 2] cycloaddition of N-but-3-...
Scheme 66: Synthesis of tricyclic thietanes via the intramolecular photo [2 + 2] cycloaddition of N-but-3-enyl...
Scheme 67: Synthesis of tetracyclic thietane 344 through the intramolecular photo [2 + 2] cycloaddition of N-[...
Scheme 68: Synthesis of tri- and tetracyclic thietanes 348, 350, and 351, through the intramolecular photo [2 ...
Scheme 69: Synthesis of tetracyclic fused thietane 354 via the photo [2 + 2] cycloaddition of vinyl 2-thioxo-3H...
Scheme 70: Synthesis of highly rigid thietane-fused β-lactams via the intramolecular photo [2 + 2] cycloadditi...
Scheme 71: Asymmetric synthesis of a highly rigid thietane-fused β-lactam 356a via the intramolecular photo [2...
Scheme 72: Diastereoselective synthesis of the thietane-fused β-lactams via the intramolecular photo [2 + 2] c...
Scheme 73: Asymmetric synthesis of thietane-fused β-lactams 356 via the intramolecular photo [2 + 2] cycloaddi...
Scheme 74: Synthesis of the bridged bis(trifluoromethyl)thietane from 2,2,4,4-tetrakis(trifluoromethyl)-1,3-di...
Scheme 75: Synthesis of the bridged-difluorothietane 368 from 2,2,4,4-tetrafluoro-1,3-dithietane (367) and qua...
Scheme 76: Synthesis of bis(trifluoromethyl)thietanes from 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane (3...
Scheme 77: Synthesis of 2,2-dimethylthio-4,4-di(trifluoromethyl)thietane (378) from 2,2,4,4-tetrakis(trifluoro...
Scheme 78: Formation of bis(trifluoromethyl)thioacetone (381) through nucleophilic attack of dithietane 363 by...
Scheme 79: Synthesis of 2,2-bis(trifluoromethyl)thietanes from 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietan...
Scheme 80: Synthesis of the bridged bis(trifluoromethyl)thietane 364 from of 2,2,4,4-tetrakis(trifluoromethyl)...
Scheme 81: Synthesis of 2,4-diiminothietanes 390 from alkenimines and 4-methylbenzenesulfonyl isothiocyanate (...
Scheme 82: Synthesis of arylidene 2,4-diiminothietanes 393 starting from phosphonium ylides 391 and isothiocya...
Scheme 83: Synthesis of thietane-2-ylideneacetates 397 through a DABCO-catalyzed formal [2 + 2] cycloaddition ...
Scheme 84: Synthesis of 3-substituted thietanes 400 from (1-chloroalkyl)thiiranes 398.
Scheme 85: Synthesis of N-(thietane-3-yl)azaheterocycles 403 and 404 through reaction of chloromethylthiirane (...
Scheme 86: Synthesis of 3-sulfonamidothietanes 406 from sulfonamides and chloromethylthiirane (398a).
Scheme 87: Synthesis of N-(thietane-3-yl)isatins 408 from chloromethylthiirane (398a) and isatins 407.
Scheme 88: Synthesis of 3-(nitrophenyloxy)thietanes 410 from nitrophenols 409 and chloromethylthiirane (398a).
Scheme 89: Synthesis of N-aryl-N-(thietane-3-yl)cyanamides 412 from N-arylcyanamides 411 and chloromethylthiir...
Scheme 90: Synthesis of 1-(thietane-3-yl)pyrimidin-2,4(1H,3H)-diones 414 from chloromethylthiirane (398a) and ...
Scheme 91: Synthesis of 2,4-diiminothietanes 418 from 2-iminothiiranes 416 and isocyanoalkanes 415.
Scheme 92: Synthesis of 2-vinylthietanes 421 from thiiranes 419 and 3-chloroallyl lithium (420).
Scheme 93: Synthesis of thietanes from thiiranes 419 and trimethyloxosulfonium iodide 424.
Scheme 94: Mechanism for synthesis of thietanes 425 from thiiranes 419 and trimethyloxosulfonium iodide 424.
Scheme 95: Synthesis of functionalized thietanes from thiiranes and dimethylsulfonium acylmethylides.
Scheme 96: Mechanism for the rhodium-catalyzed synthesis of functionalized thietanes 429 from thiiranes 419 an...
Scheme 97: Synthesis of 3-iminothietanes 440 through thermal isomerization from 4,5-dihydro-1,3-oxazole-4-spir...
Scheme 98: Synthesis of thietanes 443 from 3-chloro-2-methylthiolane (441) through ring contraction.
Scheme 99: Synthesis of an optically active thietanose 447 from D-xylose involving a ring contraction.
Scheme 100: Synthesis of optically thietane 447 via the DAST-mediated ring contraction of 448.
Scheme 101: Synthesis of the optically thietane nucleoside 451 via the ring contraction of thiopentose in 450.
Scheme 102: Synthesis of spirothietane 456 from 3,3,5,5-tetramethylthiolane-2,4-dithione (452) and benzyne (453...
Scheme 103: Synthesis of thietanes 461 via photoisomerization of 2H,6H-thiin-3-ones 459.
Scheme 104: Phosphorodithioate-mediated synthesis of 1,4-diarylthietanes 465.
Scheme 105: Mechanism of the phosphorodithioate-mediated synthesis of 1,4-diarylthietanes 465.
Scheme 106: Phosphorodithioate-mediated synthesis of trisubstituted thietanes (±)-470.
Scheme 107: Mechanism on the phosphorodithioate-mediated synthesis of trisubstituted thietanes.
Scheme 108: Phosphorodithioate-mediated synthesis of thietanes (±)-475.
Scheme 109: Phosphorodithioate-mediated synthesis of 1,2-disubstituted thietanes from aldehydes 476 and acrylon...
Scheme 110: Phosphorodithioate-mediated synthesis of 1,2-disubstituted thietanes via a one-pot three-component ...
Scheme 111: Mechanism for the phosphorodithioate-mediated synthesis of 1,2-disubstituted thietanes via three-co...
Scheme 112: Phosphorodithioate-mediated synthesis of substituted 3-nitrothietanes.
Scheme 113: Mechanism on the phosphorodithioate-mediated synthesis of 1,2-disubstituted thietanes (±)-486.
Scheme 114: Asymmetric synthesis of (S)-2-phenylthietane (497).
Scheme 115: Asymmetric synthesis of optically active 2,4-diarylthietanes.
Scheme 116: Synthesis of 3-acetamidothietan-2-one 503 via the intramolecular thioesterification of 3-mercaptoal...
Scheme 117: Synthesis of 4-substituted thietan-2-one via the intramolecular thioesterification of 3-mercaptoalk...
Scheme 118: Synthesis of 4,4-disubstituted thietan-2-one 511 via the intramolecular thioesterification of the 3...
Scheme 119: Synthesis of a spirothietan-2-one 514 via the intramolecular thioesterification of 3-mercaptoalkano...
Scheme 120: Synthesis of thiatetrahydrolipstatin starting from (S)-(−)-epichlorohydrin ((S)-142a).
Scheme 121: Synthesis of 2-phenethyl-4-(propan-2-ylidene)thietane (520) from 5-bromo-6-methyl-1-phenylhept-5-en...
Scheme 122: Synthesis of 2-phenethyl-4-(propan-2-ylidene)thietane (520) directly from S-(5-bromo-6-methyl-1-phe...
Scheme 123: Synthesis of 2-alkylidenethietanes from S-(2-bromoalk-1-en-4-yl)thioacetates.
Scheme 124: Synthesis of 2-alkylidenethietanes from S-(2-bromo/chloroalk-1-en-4-yl)thiols.
Scheme 125: Synthesis of spirothietan-3-ol 548 from enone 545 and ammonium hydrosulfide.
Scheme 126: Asymmetric synthesis of the optically active thietanoside from cis-but-2-ene-1,4-diol (47).
Scheme 127: Synthesis of 2-alkylidenethietan-3-ols 557 via the fluoride-mediated cyclization of thioacylsilanes ...
Scheme 128: Synthesis of 2-iminothietanes via the reaction of propargylbenzene (558) and isothiocyanates 560 in...
Scheme 129: Synthesis of 2-benzylidenethietane 567 via the nickel complex-catalyzed electroreductive cyclizatio...
Scheme 130: Synthesis of 2-iminothietanes 569 via the photo-assisted electrocyclic reaction of N-monosubstitute...
Scheme 131: Synthesis of ethyl 3,4-diiminothietane-2-carboxylates from ethyl thioglycolate (570) and bis(imidoy...
Scheme 132: Synthesis of N-(thietan-3-yl)-α-oxoazaheterocycles from azaheterocyclethiones and chloromethyloxira...
Scheme 133: Synthesis of thietan-3-yl benzoate (590) via the nickel-catalyzed intramolecular reductive thiolati...
Scheme 134: Synthesis of 2,2-bis(trifluoromethyl)thietane from 3,3-bis(trifluoromethyl)-1,2-dithiolane.
Scheme 135: Synthesis of thietanes from enamines and sulfonyl chlorides.
Scheme 136: Synthesis of spirothietane 603 via the [2 + 3] cycloaddition of 2,2,4,4-tetramethylcyclobutane-1,3-...
Scheme 137: Synthesis of thietane (605) from 1-bromo-3-chloropropane and sulfur.
Anthelmintic drug discovery: target identification, screening methods and the role of open science
- Frederick A. Partridge,
- Ruth Forman,
- Carole J. R. Bataille,
- Graham M. Wynne,
- Marina Nick,
- Angela J. Russell,
- Kathryn J. Else and
- David B. Sattelle
Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105
- macrocyclic lactone is an effective microfilaricide but does not kill the adult nematodes. Ivermectin must therefore be administered annually or twice-annually for many years to eliminate the parasite in the population. Progress has been impressive: onchocerciasis has been largely controlled as a public
Graphical Abstract
Figure 1: Structures of some current front-line anthelmintics discussed in this review. *Denotes the stereoge...
Figure 2: Structures of new anthelmintics drugs developed through repurposing, and new drugs or drug candidat...
Figure 3: Compounds with anthelmintic activity identified by a combination of screening against Ancylostoma c...
Figure 4: Inhibitors of S. mansoni thioredoxin glutathione reductase with anthelmintic activity [140].
Figure 5: Active compounds from anthelmintic screens using the MMV Pathogen Box. NTS: newly transformed schis...
Figure 6: Two resolution approaches to enantiopure PZQ (R)-5 discovered through A) open science and B) contra...
Activated carbon as catalyst support: precursors, preparation, modification and characterization
- Melanie Iwanow,
- Tobias Gärtner,
- Volker Sieber and
- Burkhard König
Beilstein J. Org. Chem. 2020, 16, 1188–1202, doi:10.3762/bjoc.16.104
Graphical Abstract
Figure 1: Experimental setup of ultrasonic spray pyrolysis. Reprinted with permission from [95], copyright 2006 T...
Figure 2: Overview of nitrogen-containing functional groups on the surface of activated carbons. Scheme was d...
Fluorinated phenylalanines: synthesis and pharmaceutical applications
- Laila F. Awad and
- Mohammed Salah Ayoup
Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91
- with zincate 11 using a variety of catalysts and different reaction conditions, was unsuccessful. However, coupling of 4-[bis(dimethoxybenzyl)difluoromethyl]benzyl bromide (14) with the lithium enolate of William`s lactone 15 gave the protected amino acid 16 in 80% yield. The desired protected amino
Graphical Abstract
Figure 1: Categories I–V of fluorinated phenylalanines.
Scheme 1: Synthesis of fluorinated phenylalanines via Jackson’s method.
Scheme 2: Synthesis of all-cis-tetrafluorocyclohexylphenylalanines.
Scheme 3: Synthesis of ʟ-4-[sulfono(difluoromethyl)]phenylalanine (nPt: neopentyl, TCE: trichloroethyl).
Scheme 4: Synthesis of ʟ-4-[sulfono(difluoromethyl)]phenylalanine derivatives 17.
Scheme 5: Synthesis of fluorinated Phe analogues from Cbz-protected aminomalonates.
Scheme 6: Synthesis of tetrafluorophenylalanine analogues via the 3-methyl-4-imidazolidinone auxiliary 25.
Scheme 7: Synthesis of tetrafluoro-Phe derivatives via chiral auxiliary 31.
Scheme 8: Synthesis of 2,5-difluoro-Phe and 2,4,5-trifluoro-Phe via Schöllkopf reagent 34.
Scheme 9: Synthesis of 2-fluoro- and 2,6-difluoro Fmoc-Phe derivatives starting from chiral auxiliary 39.
Scheme 10: Synthesis of 2-[18F]FPhe via chiral auxiliary 43.
Scheme 11: Synthesis of FPhe 49a via photooxidative cyanation.
Scheme 12: Synthesis of FPhe derivatives via Erlenmeyer azalactone synthesis.
Scheme 13: Synthesis of (R)- and (S)-2,5-difluoro Phe via the azalactone method.
Scheme 14: Synthesis of 3-bromo-4-fluoro-(S)-Phe (65).
Scheme 15: Synthesis of [18F]FPhe via radiofluorination of phenylalanine with [18F]F2 or [18F]AcOF.
Scheme 16: Synthesis of 4-borono-2-[18F]FPhe.
Scheme 17: Synthesis of protected 4-[18F]FPhe via arylstannane derivatives.
Scheme 18: Synthesis of FPhe derivatives via intermediate imine formation.
Scheme 19: Synthesis of FPhe derivatives via Knoevenagel condensation.
Scheme 20: Synthesis of FPhe derivatives 88a,b from aspartic acid derivatives.
Scheme 21: Synthesis of 2-(2-fluoroethyl)phenylalanine derivatives 93 and 95.
Scheme 22: Synthesis of FPhe derivatives via Zn2+ complexes.
Scheme 23: Synthesis of FPhe derivatives via Ni2+ complexes.
Scheme 24: Synthesis of 3,4,5-trifluorophenylalanine hydrochloride (109).
Scheme 25: Synthesis of FPhe derivatives via phenylalanine aminomutase (PAM).
Scheme 26: Synthesis of (R)-2,5-difluorophenylalanine 115.
Scheme 27: Synthesis of β-fluorophenylalanine via 2-amino-1,3-diol derivatives.
Scheme 28: Synthesis of β-fluorophenylalanine derivatives via the oxazolidinone chiral auxiliary 122.
Scheme 29: Synthesis of β-fluorophenylalanine from pyruvate hemiketal 130.
Scheme 30: Synthesis of β-fluorophenylalanine (136) via fluorination of β-hydroxyphenylalanine (137).
Scheme 31: Synthesis of β-fluorophenylalanine from aziridine derivatives.
Scheme 32: Synthesis of β-fluorophenylalanine 136 via direct fluorination of pyruvate esters.
Scheme 33: Synthesis of β-fluorophenylalanine via fluorination of ethyl 3-phenylpyruvate enol using DAST.
Scheme 34: Synthesis of β-fluorophenylalanine derivatives using photosensitizer TCB.
Scheme 35: Synthesis of β-fluorophenylalanine derivatives using Selectflour and dibenzosuberenone.
Scheme 36: Synthesis of protected β-fluorophenylalanine via aziridinium intermediate 150.
Scheme 37: Synthesis of β-fluorophenylalanine derivatives via fluorination of α-hydroxy-β-aminophenylalanine d...
Scheme 38: Synthesis of β-fluorophenylalanine derivatives from α- or β-hydroxy esters 152a and 155.
Scheme 39: Synthesis of a series of β-fluoro-Phe derivatives via Pd-catalyzed direct fluorination of β-methyle...
Scheme 40: Synthesis of series of β-fluorinated Phe derivatives using quinoline-based ligand 162 in the Pd-cat...
Scheme 41: Synthesis of β,β-difluorophenylalanine derivatives from 2,2-difluoroacetaldehyde derivatives 164a,b....
Scheme 42: Synthesis of β,β-difluorophenylalanine derivatives via an imine chiral auxiliary.
Scheme 43: Synthesis of α-fluorophenylalanine derivatives via direct fluorination of protected Phe 174.
Figure 2: Structures of PET radiotracers of 18FPhe derivatives.
Figure 3: Structures of melfufen (179) and melphalan (180) anticancer drugs.
Figure 4: Structure of gastrazole (JB95008, 181), a CCK2 receptor antagonist.
Figure 5: Dual CCK1/CCK2 antagonist 182.
Figure 6: Structure of sitagliptin (183), an antidiabetic drug.
Figure 7: Structure of retaglpitin (184) and antidiabetic drug.
Figure 8: Structure of evogliptin (185), an antidiabetic drug.
Figure 9: Structure of LY2497282 (186) a DPP-4 inhibitor for the treatment of type II diabetes.
Figure 10: Structure of ulimorelin (187).
Figure 11: Structure of GLP1R (188).
Figure 12: Structures of Nav1.7 blockers 189 and 190.
Towards the total synthesis of chondrochloren A: synthesis of the (Z)-enamide fragment
- Jan Geldsetzer and
- Markus Kalesse
Beilstein J. Org. Chem. 2020, 16, 670–673, doi:10.3762/bjoc.16.64
- obtained through a seven-step sequence starting from ᴅ-ribonic acid-1,4-lactone. The (Z)-vinyl bromide 4 is accessible in four steps from 4-hydroxybenzaldehyde. The pivotal cross coupling between both fragments was achieved after extensive experimentation with copper(I) iodide, K2CO3 and N,N
- )-bromide 4 we decided to use a (Z)-selective Buchwald-type reaction encouraged by the previous works of the Buchwald group on producing (E)-enamide coupling products [13][14][15]. The synthesis of the amide 3 started with TIPDS-protection of commercially available ᴅ-ribonic acid-1,4-lactone (5) (Scheme 1
Graphical Abstract
Figure 1: Retrosynthetic analysis of chondrochlorene A (1).
Scheme 1: Synthesis of amide 3 [16-20]. TIPDSCl2 = 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane, TBSOTf = tert-buty...
Scheme 2: Synthesis of (Z)-bromide 4 using a palladium-catalyzed, stereoselective dehalogenation [21-24]. TBSOTf = t...
Scheme 3: Cross coupling of amide 3 and (Z)-bromide 4 (see Table 1 for conditions).
Recent advances in photocatalyzed reactions using well-defined copper(I) complexes
- Mingbing Zhong,
- Xavier Pannecoucke,
- Philippe Jubault and
- Thomas Poisson
Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42
- the best copper-based photocatalyst, Collins and co-workers reported the synthesis of a bicyclic lactone by a PCET reaction manifold (Scheme 32) [39]. Using their methodology, the authors discovered the [Cu(I)(quinitri)(xantphos)]BF4 catalyst as the best one, which afford the cis-lactone in 79
- lactone synthesis using a copper-photocatalyzed PCET reaction. Photocatalytic Pinacol coupling reaction catalyzed by [Cu(I)(pypzs)(BINAP)]BF4. The ligands of the copper complex are omitted for clarity. Azide photosensitization using a Cu-based photocatalyst. Funding This work was partially supported by
Graphical Abstract
Scheme 1: [Cu(I)(dap)2]Cl-catalyzed ATRA reaction under green light irradiation.
Scheme 2: Photocatalytic allylation of α-haloketones.
Scheme 3: [Cu(I)(dap)2]Cl-photocatalyzed chlorosulfonylation and chlorotrifluoromethylation of alkenes.
Scheme 4: Photocatalytic perfluoroalkylchlorination of electron-deficient alkenes using the Sauvage catalyst.
Scheme 5: Photocatalytic synthesis of fluorinated sultones.
Scheme 6: Photocatalyzed haloperfluoroalkylation of alkenes and alkynes.
Scheme 7: Chlorosulfonylation of alkenes catalyzed by [Cu(I)(dap)2]Cl. aNo Na2CO3 was added. b1 equiv of Na2CO...
Scheme 8: Copper-photocatalyzed reductive allylation of diaryliodonium salts.
Scheme 9: Copper-photocatalyzed azidomethoxylation of olefins.
Scheme 10: Benzylic azidation initiated by [Cu(I)(dap)2]Cl.
Scheme 11: Trifluoromethyl methoxylation of styryl derivatives using [Cu(I)(dap)2]PF6. All redox potentials ar...
Scheme 12: Trifluoromethylation of silyl enol ethers.
Scheme 13: Synthesis of annulated heterocycles upon oxidation with the Sauvage catalyst.
Scheme 14: Oxoazidation of styrene derivatives using [Cu(dap)2]Cl as a precatalyst.
Scheme 15: [Cu(I)(dpp)(binc)]PF6-catalyzed ATRA reaction.
Scheme 16: Allylation reaction of α-bromomalonate catalyzed by [Cu(I)(dpp)(binc)]PF6 following an ATRA mechani...
Scheme 17: Bromo/tribromomethylation reaction using [Cu(I)(dmp)(BINAP)]PF6.
Scheme 18: Chlorotrifluoromethylation of alkenes catalyzed by [Cu(I)(N^N)(xantphos)]PF6.
Scheme 19: Chlorosulfonylation of styrene and alkyne derivatives by ATRA reactions.
Scheme 20: Reduction of aryl and alkyl halides with the complex [Cu(I)(bcp)(DPEPhos)]PF6. aIrradiation was car...
Scheme 21: Meerwein arylation of electron-rich aromatic derivatives and 5-exo-trig cyclization catalyzed by th...
Scheme 22: [Cu(I)(bcp)(DPEPhos)]PF6-photocatalyzed synthesis of alkaloids. aYield over two steps (cyclization ...
Scheme 23: Copper-photocatalyzed decarboxylative amination of NHP esters.
Scheme 24: Photocatalytic decarboxylative alkynylation using [Cu(I)(dq)(binap)]BF4.
Scheme 25: Copper-photocatalyzed alkylation of glycine esters.
Scheme 26: Copper-photocatalyzed borylation of organic halides. aUnder continuous flow conditions.
Scheme 27: Copper-photocatalyzed α-functionalization of alcohols with glycine ester derivatives.
Scheme 28: δ-Functionalization of alcohols using [Cu(I)(dmp)(xantphos)]BF4.
Scheme 29: Photocatalytic synthesis of [5]helicene and phenanthrene.
Scheme 30: Oxidative carbazole synthesis using in situ-formed [Cu(I)(dmp)(xantphos)]BF4.
Scheme 31: Copper-photocatalyzed functionalization of N-aryl tetrahydroisoquinolines.
Scheme 32: Bicyclic lactone synthesis using a copper-photocatalyzed PCET reaction.
Scheme 33: Photocatalytic Pinacol coupling reaction catalyzed by [Cu(I)(pypzs)(BINAP)]BF4. The ligands of the ...
Scheme 34: Azide photosensitization using a Cu-based photocatalyst.
Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0
- Bernd Strehmel,
- Christian Schmitz,
- Ceren Kütahya,
- Yulian Pang,
- Anke Drewitz and
- Heinz Mustroph
Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40
- distributes in literature but is wrong because protons do not exist alone and data related to pH-values relate only to aqueous solutions. Ring opening by rhodamine B lactone quantitatively probed formation conjugate acid by formation of rhodamine B [5]. We interpret the term conjugate acid as a species in
Graphical Abstract
Scheme 1: Structural patterns of several symmetric cyanines relating to trimethines (I), pentamethines (II), ...
Scheme 2: 1-Substituted 2,3,3-trimethylindolium-, 2,3,3-benzo[e]indolium-, and 2,3,3-benzo[c,d]indolium salts...
Scheme 3: Substitution of the chlorine substituent at the meso-position by a stronger nucleophilic moiety B [68].
Scheme 4: Structure of alternative chain builders for synthesis of heptamethines.
Figure 1: Simplified process chart of photophysical processes occurring in NIR absorbers.
Scheme 5: Chemical structure of the electron acceptors that were from iodonium cations 88 and triazines 89.
Figure 2: Photoinduced electron transfer under different scenarios in which each example exhibits an intrinsi...
Scheme 6: Photoexcited absorber 33 results in reaction with an iodonium cation in the respective cation radic...
Scheme 7: Reaction scheme of absorbers comprising in the molecules center a five ring bridged moiety. This le...
Scheme 8: Structure of donor compounds used in a three component system.
Figure 3: Cationic photopolymerization of an epoxide (Epikote 828) initiated by excitation of the absorber 36...
Scheme 9: Different modes of photoinitiated ATRP using UV, visible and NIR light.
Scheme 10: The structure of Sens used in photo-ATRP.
Figure 4: Comparison of the GPC traces of precursor PMMA with a) chain extended PMMA and b) PMMA-b-PS. Condit...
Figure 5: Spectral changes of the solution of 48 in the presence of [Cu(L)]Br2 (L: tris(2-pyridylmethyl)amine...
Scheme 11: Photoinduced CuAAC reactions in which photochemical reactions result in formation of the Cu(I) cata...
Scheme 12: Model reaction between benzyl azide and phenyacetylene using the absorber 48 as NIR sensitizer at 7...
Figure 6: Block copolymerization of the precursors PS-N3 and Alkyne-PCL results in the block copolymer PS-b-P...
Figure 7: UV–vis–NIR absorption changes of the solution of 48 in the presence of PMDETA, phenylacetylene and ...
Scheme 13: Workflow to design and process new materials in a setup based on an intelligent DoE to develop tech...
Scheme 14: Illustration of the iDoE setting up experiments suggested and analyzed by the A.I. After defining t...
Scheme 15: Classification of the factors for the formation of polymer networks by NIR-photocuring depending on...
Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid
- Kaj M. van Vliet,
- Nicole S. van Leeuwen,
- Albert M. Brouwer and
- Bas de Bruin
Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38
- form in case of fac-[Ir(ppy)3]), which was proven by mass spectrometry and EPR spectroscopy for one of the catalysts (N,N-5,10-di(2-naphthalene)-5,10-dihydrophenazine) used in this work. The generation of HCl resulting from lactone formation could be an additional problem for organometallic photoredox
- catalysts used in this reaction. In an attempt to trap one of the radical intermediates with TEMPO, we observed a compound indicating the generation of a chloromethyl radical. Keywords: ATRA; catalysis; chloroacetic acid; lactone; photoredox; Introduction Monochloroacetic acid is an industrially important
- , Kokotos and co-workers published a visible light photoredox catalyzed lactone formation from iodoacetic acid and alkenes [29] (Scheme 1). In addition, it has been shown that monochloroacetic acid can be reduced by hydrated electrons [30][31]. The group of Goez developed a strategy for the photoredox
Graphical Abstract
Figure 1: A part of the industry around monochloroacetic acid.
Scheme 1: Redox based activation of haloacetic acid.
Figure 2: Cyclic voltammogram of monochloroacetic acid and ferrocene with 0.1 M [TBA][PF6] in MeCN. The poten...
Scheme 2: Initial attempts for lactone formation by photoredox catalysis.
Scheme 3: The photoredox reaction of TEMPO with monochloroacetic acid catalyzed by fac-[Ir(ppy)3].
Figure 3: EPR spectra measured (black) and simulated (red) based on the structure of the oxidized photoredox ...
Scheme 4: Two possible acid-assisted, reductive activation pathways of monochloroacetic acid (A–H = acid).
Figure 4: Reaction mixtures after overnight irradiation of (A) 4-chloro-4-phenylbutanoic acid (3) and fac-[Ir...
Scheme 5: Substrate scope of styrene derivatives in the photoredox reaction with monochloroacetic acid. Yield...
Scheme 6: Proposed reaction mechanism.
Scheme 7: The photoredox formation of 1-(chloromethoxy)-2,2,6,6-tetramethylpiperidine.
Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors
- Delphine Pichon,
- Jennifer Morvan,
- Christophe Crévisy and
- Marc Mauduit
Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24
- enantioenriched products (up to 99% ee) were successfully converted to relevant molecules, such as trans-whisky lactone [43]. In 2003, Hoveyda and Hird reported the first 1,4-addition of alkylmetal nucleophiles to α,β-unsaturated N-acyloxazolidinones (Scheme 19) [47]. The chiral triamidophosphane ligand L15a as a
Graphical Abstract
Scheme 1: Competitive side reactions in the Cu ECA of organometallic reagents to α,β-unsaturated aldehydes.
Scheme 2: Cu-catalyzed ECA of α,β-unsaturated aldehydes with phosphoramidite- (a) and phosphine-based ligands...
Scheme 3: One-pot Cu-catalyzed ECA/organocatalyzed α-substitution of enals.
Scheme 4: Combination of copper and amino catalysis for enantioselective β-functionalizations of enals.
Scheme 5: Optimized conditions for the Cu ECAs of R2Zn, RMgBr, and AlMe3 with α,β-unsaturated aldehydes.
Scheme 6: CuECA of Grignard reagents to α,β-unsaturated thioesters and their application in the asymmetric to...
Scheme 7: Improved Cu ECA of Grignard reagents to α,β-unsaturated thioesters, and their application in the as...
Scheme 8: Catalytic enantioselective synthesis of vicinal dialkyl arrays via Cu ECA of Grignard reagents to γ...
Scheme 9: 1,6-Cu ECA of MeMgBr to α,β,γ,δ-bisunsaturated thioesters: an iterative approach to deoxypropionate...
Scheme 10: Tandem Cu ECA/intramolecular enolate trapping involving 4-chloro-α,β-unsaturated thioester 22.
Scheme 11: Cu ECA of Grignard reagents to 3-boronyl α,β-unsaturated thioesters.
Scheme 12: Cu ECA of alkylzirconium reagents to α,β-unsaturated thioesters.
Scheme 13: Conversion of acylimidazoles into aldehydes, ketones, acids, esters, amides, and amines.
Scheme 14: Cu ECA of dimethyl malonate to α,β-unsaturated acylimidazole 31 with triazacyclophane-based ligand ...
Scheme 15: Cu/L13-catalyzed ECA of alkylboranes to α,β-unsaturated acylimidazoles.
Scheme 16: Cu/hydroxyalkyl-NHC-catalyzed ECA of dimethylzinc to α,β-unsaturated acylimidazoles.
Scheme 17: Stereocontrolled synthesis of 3,5,7-all-syn and anti,anti-stereotriads via iterative Cu ECAs.
Scheme 18: Stereocontrolled synthesis of anti,syn- and anti,anti-3,5,7-(Me,OR,Me) units via iterative Cu ECA/B...
Scheme 19: Cu-catalyzed ECA of dialkylzinc reagents to α,β-unsaturated N-acyloxazolidinones.
Scheme 20: Cu/phosphoramidite L16-catalyzed ECA of dialkylzincs to α,β-unsaturated N-acyl-2-pyrrolidinones.
Scheme 21: Cu/(R,S)-Josiphos (L9)-catalyzed ECA of Grignard reagents to α,β-unsaturated amides.
Scheme 22: Cu/Josiphos (L9)-catalyzed ECA of Grignard reagents to polyunsaturated amides.
Scheme 23: Cu-catalyzed ECA of trimethylaluminium to N-acylpyrrole derivatives.
Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose
- Lukáš Kerner and
- Paul Kosma
Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2
- lactone with the lithium salt of dimethyl methylphosphonate followed by an elimination step of the resulting hemiketal, leading to the corresponding exo- and endo-glycal derivatives. The ensuing selective monodemethylation and hydrogenolysis of the benzyl groups and reduction of the 4-azido group gave the
- Ara4N transferase reacted with the equatorial phosphodiester lipid, we opted to use lactone 4 as a suitable precursor for C-glycosyl phosphonates, based on literature precedents [10][20][21]. Thus, a modified Swern oxidation of lactol 3 with acetic anhydride in DMSO afforded a near-quantitative yield of
- lactone 4, which, however, was unstable towards chromatographic purification and used as crude material after lyophilization to remove the solvent. Coupling of 4 with the lithium salt of dimethyl methylphosphonate (5) in THF afforded the β-anomeric ketol phosphonate derivative 6 in 57% yield. The axial
Graphical Abstract
Figure 1: Modification of lipid A by ArnT.
Scheme 1: Phosphonate and glycal synthesis.
Scheme 2: Synthesis of methyl phosphonate 11 and octyl phosphonates 16 and 17.
A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones
- Daniel P. Pienaar,
- Kamogelo R. Butsi,
- Amanda L. Rousseau and
- Dean Brady
Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287
- solubility of both the KOt-Bu base and the acetonitrile derived KCH2CN salt. This effectively accelerates the generation of the latter and as such, its reaction with the lactone (or ester) carbonyl carbon. By increasing the solubility of the conjugate base salt, the pKa of acetonitrile in the ethereal
- alkoxide anions. This reduces the occurrence of undesirable side-reactions, e.g., intermolecular aldol reaction, lactone/ketonitrile product dimerization and ring-opening polymerization. The application of this method to produce the analogous hemiketal 6 from γ-butyrolactone was not as efficient. Although
- from lactone to 20% (Scheme 2). Due to the interest in the potential preparation of pyrimidines from β-ketonitriles and guanidine [18], we wanted to test the general applicability of this method for access to a variety of alkyl and aryl-substituted β-ketonitriles (as summarized in Table 1). When we
Graphical Abstract
Scheme 1: Proposed retrosynthesis of the free diol 1.
Scheme 2: Preparation of O-unprotected, trifunctionalized synthons from lactones.
Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis
- Heather J. Lacey,
- Cameron L. M. Gilchrist,
- Andrew Crombie,
- John A. Kalaitzis,
- Daniel Vuong,
- Peter J. Rutledge,
- Peter Turner,
- John I. Pitt,
- Ernest Lacey,
- Yit-Heng Chooi and
- Andrew M. Piggott
Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256
- File 1) yielded ten drimane metabolites shown in Figure 1: one trihydroxylated drimane sesquiterpenoid lactone, nanangenine A (1), four drimane lactones bearing C6/C8 acyl chains, nanangenines B, C, D and E (2, 4, 5 and 6), two acylated drimanes bearing isomeric lactones, isonanangenines B and D (3 and
- ), three methyl groups (C-13, C-14, C-15) and three hydroxy groups (1-OH, 6-OH, 9-OH). Detailed analysis of the 2D NMR data for 1 (Table S3 in Supporting Information File 1) confirmed the presence of a drimane sesquiterpenoid lactone scaffold. A search of the literature revealed 1 to be almost identical to
- revealed the only difference to be the position of the lactone carbonyl group, which was determined to be at C-12 instead of C-11 based on key HBMC correlations from H-7 to C-12 and 9-OH to C-11. Therefore, the structure of 3 was assigned as shown in Figure 1. Compound 3 was previously reported in 2013 as
Graphical Abstract
Figure 1: Structures of nanangenines 1–10 isolated from A. nanangensis.
Figure 2: Putative nanangenine biosynthetic gene cluster in A. nanangensis MST-FP2251 and homologs identified...
Figure 3: Putative biosynthetic pathway to the nanangenines.
Synthetic terpenoids in the world of fragrances: Iso E Super® is the showcase
- Alexey Stepanyuk and
- Andreas Kirschning
Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252
- ]. Oxidation, iodocarboxylation and elimination yielded the lactone 43. A series of functional group manipulations provided enone 44, which underwent a cuprate-mediated Michael addition and liberation of the aldehyde 46 upon ozonolysis. After intramolecular aldol condensation the resulting enone 47 was
Graphical Abstract
Figure 1: Terpene constituents 1–9 found in geranium and bergamot oils and specified odours of individual com...
Figure 2: Other selected mono- and sesquiterpenes (10–26) as fragrance materials [6].
Figure 3: Main constituents of natural iris oil: irone (27).
Scheme 1: First synthesis of ionone (30) [11].
Scheme 2: First synthesis of Ambrelux (32) [14].
Scheme 3: Industrial synthesis of myrcene (1) by pyrolysis of β-pinene (8).
Scheme 4: First synthesis of Iso E Super® (33), Iso E Super Plus® (34) and Georgywood® (35) as a mixture of i...
Figure 4: Iso E Super® region of GC spectra of Molecule 01 (left, 75 €–100 € per 100 mL; march 2019), a low-p...
Scheme 5: First synthetic route to (−)-Georgywood® (35) by Corey and Hong [33].
Scheme 6: First synthetic route to the odour-active (+)-enantiomer of Iso E Super Plus® (+)-34 [33].
Scheme 7: Analysis of the isomerisation process and formation of products. Most importantly, Iso E Super® (33...
Scheme 8: Isomerisation using additives such as alcohols or carboxylic acids. The product with the γ-position...
Scheme 9: Iso E Super Plus® (34) can undergo a third cyclisation to tetrahydrofuran 59 through compound rac-53...
Figure 5: (Adapted from ref. [8]) Ionone (30, 1893, odour threshold: 0.8 ng L−1), koavone (1982, odour threshold...
Figure 6: Branched, terpene-like cyclohexene derivatives, that are synthetic fragrance components: 60: Iso da...
Scheme 10: New unnatural terpenoid 70 from unnatural farnesyl pyrophosphate derivative 69 and comparison with ...
Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides
- José Brango-Vanegas,
- Luan A. Martinho,
- Lucinda J. Bessa,
- Andreanne G. Vasconcelos,
- Alexandra Plácido,
- Alex L. Pereira,
- José R. S. A. Leite and
- Angelo H. L. Machado
Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247
- was based on the conservation of the 16-membered macrocyclic scaffold and the apolar tripeptidyl moiety found in the solonamides. Both features are important to guarantee the interference with S. aureus QS [12][13][14][15]. The ester linkage of the lactone core was substituted by the sulfide group
- File 1). Three main absorption bands could be readily observed around 3280, 1650 and 1520 cm−1. The first one was assigned to the stretch for N–H bonds of the peptide linkage. The stretch for the lactam and lactone C=O bonds gives rise to the broad absorption close to 1650 cm−1. The lowering on the
- wavenumber values for the lactone C=O stretch was also observed for bands assigned to the C=C bonds as consequence of their conjugation. Evaluation of the growth inhibition and hemolytic activity of S. aureus for the solonamide analogues Initially, the antibacterial activity of all analogues 9 was tested by
Graphical Abstract
Figure 1: Chemical structure of solonamides and autoinducing peptides (AIP).
Scheme 1: Macrocyclization strategy based on SN2’.
Scheme 2: Chemical synthesis of the MBH adducts 2 and their carboxylic acids 3.
Scheme 3: Chemical synthesis of the linear peptidomimetics 8.
Scheme 4: Macrocyclization strategy based on SN2’ reaction to affords the solonamide analogues 9 and their ov...
Figure 2: Effect of compounds 9e and 9g at three concentrations on the hemolysis production by S. aureus ATCC...
Figure 3: Inhibition of hemolysis (%) on human red blood cells caused by S. aureus ATCC 25923 after being in ...
Figure 4: Cell viability of human fibroblast exposed to compounds 9e (A) and 9g (B) for 24 and 48 hours. The ...
Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter
- Sachin S. Burade,
- Sushil V. Pawar,
- Tanmoy Saha,
- Navanath Kumbhar,
- Amol S. Kotmale,
- Manzoor Ahmad,
- Pinaki Talukdar and
- Dilip D. Dhavale
Beilstein J. Org. Chem. 2019, 15, 2419–2427, doi:10.3762/bjoc.15.234
- showed a broad band at 3444–3421 cm−1 indicating the presence of -NHs of amine/amide functionalities. The bands at 1740 and 1688 cm−1 were assigned to the lactone carbonyl and amide (as well as imine) groups, respectively. In the 1H NMR spectrum, the downfield signals at δ 9.03 and 8.52 ppm were assigned
- to the amide NH(I) and NH(II), respectively. The signal at δ 1.80 ppm, integrating for two protons, was assigned to the presence of an NH2 functionality. In the 13C NMR spectrum, the appearance of signals at δ 170.8, 170.6 and 166.7 ppm were assigned to the lactone/amide carbonyl functionalities. The
- δ 2.0 ppm, integrating for three protons, was assigned to the NHCOCH3. In the 13C NMR spectrum, the appearance of five signals in the downfield region (at δ 171.6, 170.9, 167.5, 165.0, and 164.0 ppm) indicated the presence of three amides, lactone carbonyl and imine carbon (-C=N) suggesting the
Graphical Abstract
Figure 1: Oxazolone pseudodipeptide 1 and tetrapeptide 2a.
Scheme 1: Synthesis of linear azido ester dipeptide 5 and tetrapeptide 7.
Scheme 2: Synthesis of oxazolone pseudopeptides 1, 2a and 2b.
Figure 2: Characteristic NOEs of 2a.
Figure 3: DMSO titration study of 2a.
Figure 4: 1H NMR temperature study of 2a.
Figure 5: Optimized helical conformations of (A) 2a, (B) 2b and (C) 9.
Figure 6: Ion transport activity (A) for 1, (B) for 2a, across EYPC-LUVs HPTS.
Figure 7: Cation (A) and anion (B) transport activity of 2a.
Figure 8:
Comparison of the ion transport activity of 2a and 2b at 20 µM across EYPC-LUVs![[Graphic 2]](/bjoc/content/inline/1860-5397-15-234-i4.svg?max-width=637&scale=1.18182)
lucigenin (A). Conce...
An overview of the cycloaddition chemistry of fulvenes and emerging applications
- Ellen Swan,
- Kirsten Platts and
- Anton Blencowe
Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209
- (3b’ and 6b’) and anti-aromatic (4a’ and 5a’) ring currents. Reaction of 6,6-dimethylpentafulvene with singlet state oxygen to form an enol lactone via the multistep rearrangement proposed by Harada et al. (supporting information was not provided) [51]. Photosensitized oxygenation of 8
Graphical Abstract
Figure 1: General structure of fulvenes, named according to the number of carbon atoms in their ring. Whilst ...
Figure 2: Generic structures of commonly referenced heteropentafulvenes, named according to the heteroatom su...
Scheme 1: Resonance structures of (a) pentafulvene and (b) heptafulvene showing neutral (1 and 2), dipolar (1a...
Scheme 2: Resonance structures of (a) pentafulvenes and (b) heptafulvenes showing the influence of EDG and EW...
Scheme 3: Reaction of 6,6-dimethylpentafulvene with singlet state oxygen to form an enol lactone via the mult...
Scheme 4: Photosensitized oxygenation of 8-cyanoheptafulvene with singlet state oxygen to afford 1,4-epidioxi...
Figure 3: A representation of HOMO–LUMO orbitals of pentafulvene and the influence of EWG and EDG substituent...
Scheme 5: Reactions of (a) 6,6-dimethylpentafulvene participating as 2π and 4π components in cycloadditions w...
Scheme 6: Proposed mechanism for the [6 + 4] cycloaddition of tropone with dimethylfulvene via an ambimodal [...
Scheme 7: Triafulvene dimerization through the proposed 'head-to-tail' mechanism. The dipolar transition stat...
Scheme 8: Dimerization of pentafulvenes via a Diels–Alder cycloaddition pathway whereby one fulvene acts as a...
Scheme 9: Dimerization of pentafulvenes via frustrated Lewis pair chemistry as reported by Mömming et al. [116].
Scheme 10: Simplified reaction scheme for the formation of kempane from an extended-chain pentafulvene [127].
Scheme 11: The enantioselective (>99% ee), asymmetric, catalytic, intramolecular [6 + 2] cycloaddition of fulv...
Scheme 12: Intramolecular [8 + 6] cycloaddition of the heptafulvene-pentafulvene derivative [22,27].
Scheme 13: Reaction scheme for (a) [2 + 2] cycloaddition of 1,2-diphenylmethylenecyclopropene and 1-diethylami...
Scheme 14: Diels–Alder cycloaddition of pentafulvenes derivatives participating as dienes with (i) maleimide d...
Scheme 15: Generic schemes showing pentafulvenes participating as dienophiles in Diels–Alder cycloadditions wi...
Scheme 16: Reaction of 8,8-dicyanoheptafulvene and styrene derivatives to afford [8 + 2] and [4 + 2] cycloaddu...
Scheme 17: Reaction of 6-aminofulvene and maleic anhydride, showing observed [6 + 2] cycloaddition; the [4 + 2...
Scheme 18: Schemes for Diels–Alder cycloadditions in dynamic combinatorial chemistry reported by Boul et al. R...
Scheme 19: Polymerisation and dynamer formation via Diels–Alder cycloaddition between fulvene groups in polyet...
Scheme 20: Preparation of hydrogels via Diels–Alder cycloaddition with fulvene-conjugated dextran and dichloro...
Scheme 21: Ring-opening metathesis polymerisation of norbornene derivatives derived from fulvenes and maleimid...
Characterization of two new degradation products of atorvastatin calcium formed upon treatment with strong acids
- Jürgen Krauß,
- Monika Klimt,
- Markus Luber,
- Peter Mayer and
- Franz Bracher
Beilstein J. Org. Chem. 2019, 15, 2085–2091, doi:10.3762/bjoc.15.206
- /dehydration process in the side chain), treatment with conc. aqueous hydrochloric acid gave a complex, bridged molecule under C–C-bond formation of the lactone moiety with the pyrrole, migration of the isopropyl group and loss of the carboxanilide residue. The novel degradation products were characterized by
- process (stereoisomers, products resulting from impure starting materials or side reactions), and only one of these impurities, lactone 2, is most likely a degradation product, resulting from acid-mediated lactonization of the 3,5-dihydroxyheptanoate side chain. A couple of previous publications deal with
- -dihydroxyheptanoate side chain under moderately acidic conditions (0.1 M HCl) [11][12][13][14]. Shah et al. [15] identified six additional decomposition products upon treatment with 0.1 M HCl at 80 °C for 24 h, among which the dehydrated lactone 3 was dominating, accompanied by minor amounts of products arising from
Graphical Abstract
Figure 1: Atorvastatin calcium trihydrate (1) and previously published decomposition products arising from tr...
Scheme 1: Formation of novel artefacts 6 and 7 under extremely strong acidic conditions.
Figure 2: Top: Molecular structure of artefact 6. Shown here is the molecular structure of one of three indep...
Figure 3: Separation of atorvastatin (1; retention time: 5.8 min) from the four decomposition products 2 (ret...
Scheme 2: Proposed mechanism for the formation of desamidated product 7.
Scheme 3: Proposed mechanism for the formation of bridged product 6 under cyclization, isopropyl migration an...
Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana
- Chin-Soon Phan,
- Hang Li,
- Simon Kessler,
- Peter S. Solomon,
- Andrew M. Piggott and
- Yit-Heng Chooi
Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198
- chromatographed repeatedly with silica gel and RP-HPLC to afford four new sativene-type sesquiterpenoids, bipolenins K–N (1–4), along with eight previously reported compounds (5–12), which were identified as sativene-type sesquiterpenoids prehelminthosporol lactone (5) [1], helminthosporic acid (6) [1
- , 1.88, 2.65 and 3.77), which are typical resonances for sativene-type sesquiterpenoids. The NMR data for 1 were very similar to those for prehelminthosporol lactone (5) except for the replacement of a methine group (δC 32.1; δH 1.42) at C-9 in 5 with a hydroxylated quaternary carbon (δC 73.1) in 1. This
- with reduction of the lactone ring to the dialcohol and dihydroxylation of the Δ2,12 double bond. Detailed analysis of the 2D NMR data for 4 (Figure 2) confirmed the seco-sativene-type scaffold. The relative configurations at C-1, C-3, C-6, C-7 and C-13 were determined to be the same as those of 1–3
Graphical Abstract
Figure 1: Structures of compounds 1–12 isolated from B. sorokiniana.
Figure 2: Key 2D NMR correlations of bipolenins K–N (1–4).
Figure 3: Key NOESY correlations of bipolenins K–N (1–4).
Figure 4: (a) Experimental ECD spectrum of 1 (MeOH) compared to TDDFT-calculated spectra (B3LYP-D3/def2-TZVPP...
Figure 5: Relationship of sesquiterpenoids isolated in this study. A) Different groups of sativene/longifolen...
