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Search for "tartaric acid" in Full Text gives 36 result(s) in Beilstein Journal of Organic Chemistry.
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...
Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach
- Dileep Kumar Singh and
- Rajesh Kumar
Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71
- amines 52 with 2,5-DMTHF (2) under a L-(+)-tartaric acid-choline chloride based deep eutectic solvent as green medium (Scheme 25a). Deep eutectic solvents (DESs) are mainly synthesized by mixing quaternary ammonium salts and hydrogen-bond donors. In this study, various combinations of salts and hydrogen
- bond donating groups were investigated. Among these, the DES prepared by mixing quaternary ammonium salts choline chloride (ChCl) and the hydrogen-bond donor L-(+)-tartaric acid gives the best result. Moreover, L-(+)-tartaric acid–ChCl acts as both solvent and catalyst for pyrrole synthesis. This
- -substituted pyrroles 43. Synthesis of N-substituted pyrroles 45 by using Co catalyst Co/NGr-C@SiO2-L. Zinc-catalyzed synthesis of N-arylpyrroles 47. Silica sulfuric acid-catalyzed synthesis of pyrrole derivatives 49. Bismuth nitrate-catalyzed synthesis of pyrroles 51. L-(+)-tartaric acid-choline chloride
Graphical Abstract
Figure 1: Various pyrrole containing molecules.
Scheme 1: Various synthestic protocols for the synthesis of pyrroles.
Figure 2: A tree-diagram showing various conventional and green protocols for Clauson-Kaas pyrrole synthesis.
Scheme 2: A general reaction of Clauson–Kaas pyrrole synthesis and proposed mechanism.
Scheme 3: AcOH-catalyzed synthesis of pyrroles 5 and 7.
Scheme 4: Synthesis of N-substituted pyrroles 9.
Scheme 5: P2O5-catalyzed synthesis of N-substituted pyrroles 11.
Scheme 6: p-Chloropyridine hydrochloride-catalyzed synthesis of pyrroles 13.
Scheme 7: TfOH-catalyzed synthesis of N-sulfonylpyrroles 15, N-sulfonylindole 16, N-sulfonylcarbazole 17.
Scheme 8: Scandium triflate-catalyzed synthesis of N-substituted pyrroles 19.
Scheme 9: MgI2 etherate-catalyzed synthesis and proposed mechanism of N-arylpyrrole derivatives 21.
Scheme 10: Nicotinamide catalyzed synthesis of pyrroles 23.
Scheme 11: ZrOCl2∙8H2O catalyzed synthesis and proposed mechanism of pyrrole derivatives 25.
Scheme 12: AcONa catalyzed synthesis of N-substituted pyrroles 27.
Scheme 13: Squaric acid-catalyzed synthesis and proposed mechanism of N-substituted pyrroles 29.
Figure 3: Reusability of catalyst γ-Fe2O3@SiO2-Sb-IL in six cycles.
Scheme 14: Magnetic nanoparticle-supported antimony catalyst used in the synthesis of N-substituted pyrroles 31...
Scheme 15: Iron(III) chloride-catalyzed synthesis of N-substituted pyrroles 33.
Scheme 16: Copper-catalyzed Clauson–Kaas synthesis and mechanism of pyrroles 35.
Scheme 17: β-CD-SO3H-catalyzed synthesis and proposed mechanism of pyrroles 37.
Figure 4: Recyclability of β-cyclodextrin-SO3H.
Scheme 18: Solvent-free and catalyst-free synthesis and plausible mechanism of N-substituted pyrroles 39.
Scheme 19: Nano-sulfated TiO2-catalyzed synthesis of N-substituted pyrroles 41.
Figure 5: Plausible mechanism for the formation of N-substituted pyrroles catalyzed by nano-sulfated TiO2 cat...
Scheme 20: Copper nitrate-catalyzed Clauson–Kaas synthesis and mechanism of N-substituted pyrroles 43.
Scheme 21: Synthesis of N-substituted pyrroles 45 by using Co catalyst Co/NGr-C@SiO2-L.
Scheme 22: Zinc-catalyzed synthesis of N-arylpyrroles 47.
Scheme 23: Silica sulfuric acid-catalyzed synthesis of pyrrole derivatives 49.
Scheme 24: Bismuth nitrate-catalyzed synthesis of pyrroles 51.
Scheme 25: L-(+)-tartaric acid-choline chloride-catalyzed Clauson–Kaas synthesis and plausible mechanism of py...
Scheme 26: Microwave-assisted synthesis of N-substituted pyrroles 55 in AcOH or water.
Scheme 27: Synthesis of pyrrole derivatives 57 using a nano-organocatalyst.
Figure 6: Nano-ferric supported glutathione organocatalyst.
Scheme 28: Microwave-assisted synthesis of N-substituted pyrroles 59 in water.
Scheme 29: Iodine-catalyzed synthesis and proposed mechanism of pyrroles 61.
Scheme 30: H3PW12O40/SiO2-catalyzed synthesis of N-substituted pyrroles 63.
Scheme 31: Fe3O4@-γ-Fe2O3-SO3H-catalyzed synthesis of pyrroles 65.
Scheme 32: Mn(NO3)2·4H2O-catalyzed synthesis and proposed mechanism of pyrroles 67.
Scheme 33: p-TsOH∙H2O-catalyzed (method 1) and MW-assisted (method 2) synthesis of N-sulfonylpyrroles 69.
Scheme 34: ([hmim][HSO4]-catalyzed Clauson–Kaas synthesis of pyrroles 71.
Scheme 35: Synthesis of N-substituted pyrroles 73 using K-10 montmorillonite catalyst.
Scheme 36: CeCl3∙7H2O-catalyzed Clauson–Kaas synthesis of pyrroles 75.
Scheme 37: Synthesis of N-substituted pyrroles 77 using Bi(NO3)3∙5H2O.
Scheme 38: Oxone-catalyzed synthesis and proposed mechanism of N-substituted pyrroles 79.
Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates
- Bastian Jakob,
- Nico Schneider,
- Luca Gengenbach and
- Georg Manolikakes
Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52
- investigate the influence of various fluoride scavengers as additives in the three-component process [25][26]. An extensive study (not shown), revealed that most common scavengers either led to a decreased yield, a decreased stereoselectivity or a combination of both. Yet a combination of CaCO3, tartaric acid
Graphical Abstract
Figure 1: Biologically active molecules containing α-arylglycine motifs (highlighted in green and blue).
Scheme 1: The Petasis reaction – fundamental reactivities and recent developments.
Scheme 2: Observations from previous studies and mechanistic rationale.
Scheme 3: Initial experiments.
Scheme 4: Reaction scope – aryltrifluoroborates (yields and enantiomeric ratios in parentheses refer to our p...
Scheme 5: Synthesis of both enantiomers of arylglycine building block 18.
Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures
- Sangram Gore,
- Sundarababu Baskaran and
- Burkhard König
Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37
- of 5-unsubstituted dihydropyrimidinones from β,γ-unsaturated ketoesters in low melting ʟ-(+)-tartaric acid–N,N-dimethylurea mixtures is reported. This solvent-free method is very general and provides easy access to 5-unsubstituted dihydropyrimidinone-4-carboxylate derivatives in good yields
- urea derivatives with β,γ-unsaturated ketoesters and subsequent intramolecular condensation could lead to 5-unsubstituted DHPM derivatives. β,γ-Unsaturated ketoester 7, derived from benzaldehyde and pyruvic acid [40], on exposure to ʟ-(+)-tartaric acid–N,N-dimethylurea (DMU) melt underwent smooth
- and the results are summarized in Table 1. The electron-rich (E)-ethyl 4-(4-methoxyphenyl)-2-oxobut-3-enoate (11) furnished the corresponding 5-unsubsituted DHPM derivative 12 on treatment with the ʟ-(+)-tartaric acid–DMU melt in very good yield (entry 3, Table 1). Moreover, electron-deficient β,γ
Synthetic strategies toward 1,3-oxathiolane nucleoside analogues
- Umesh P. Aher,
- Dhananjai Srivastava,
- Girij P. Singh and
- Jayashree B. S
Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182
Graphical Abstract
Figure 1: Representative modified 1,3-oxathiolane nucleoside analogues.
Figure 2: Mechanism of antiviral action of 1,3-oxathiolane nucleosides, 3TC (1) and FTC (2), as chain termina...
Figure 3: Synthetic strategies for the construction of the 1,3-oxathiolane sugar ring.
Scheme 1: Synthesis of 4 from benzoyloxyacetaldehyde (3a) and 2-mercapto-substituted dimethyl acetal 3na.
Scheme 2: Synthesis of 8 from protected glycolic aldehyde 3b and 2-mercaptoacetic acid (3o).
Scheme 3: Synthesis of 20 from ᴅ-mannose (3c).
Scheme 4: Synthesis of 20 from 1,6-thioanhydro-ᴅ-galactose (3d).
Scheme 5: Synthesis of 8 from 2-(tert-butyldiphenylsilyloxy)methyl-5-oxo-1,2-oxathiolane (3m).
Scheme 6: Synthesis of 20a from ʟ-gulose derivative 3f.
Scheme 7: Synthesis of 31 from (+)-thiolactic acid 3p and 2-benzoyloxyacetaldehyde (3a).
Scheme 8: Synthesis of 35a from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g) hydrate.
Scheme 9: Synthetic routes toward 41 through Pummerer reaction from methyl 2-mercaptoacetate (3j) and bromoac...
Scheme 10: Strategy for the synthesis of 2,5-substituted 1,3-oxathiolane 41a using 4-nitrobenzyl glyoxylate an...
Scheme 11: Synthesis of 44 by a resolution method using Mucor miehei lipase.
Scheme 12: Synthesis of 45 from benzoyloxyacetaldehyde (3a) and 2-mercaptoacetaldehyde bis(2-methoxyethyl) ace...
Scheme 13: Synthesis of 46 from 2-mercaptoacetaldehyde bis(2-methoxyethyl) acetal (3nc) and diethyl 3-phosphon...
Scheme 14: Synthesis of 48 from 1,3-dihydroxyacetone dimer 3l.
Scheme 15: Approach toward 52 from protected alkene 3rb and lactic acid derivative 51 developed by Snead et al....
Scheme 16: Recent approach toward 56a developed by Kashinath et al.
Scheme 17: Synthesis of 56a from ʟ-menthyl glyoxylate (3h) hydrate by DKR.
Scheme 18: Possible mechanism with catalytic TEA for rapid interconversion of isomers.
Scheme 19: Synthesis of 35a by a classical resolution method through norephedrine salt 58 formation.
Scheme 20: Synthesis of 63 via [1,2]-Brook rearrangement from silyl glyoxylate 61 and thiol 3nb.
Scheme 21: Combined use of STS and CAL-B as catalysts to synthesize an enantiopure oxathiolane precursor 65.
Scheme 22: Synthesis of 1 and 1a from glycolaldehyde dimer 64 and 1,4-dithiane-2,5-diol (3q) using STS and CAL...
Scheme 23: Synthesis of 68 by using Klebsiella oxytoca.
Scheme 24: Synthesis of 71 and 72 using Trichosporon taibachii lipase and kinetic resolution.
Scheme 25: Synthesis of 1,3-oxathiolan-5-ones 77 and 78 via dynamic covalent kinetic resolution.
Figure 4: Pathway for glycosidic bond formation.
Scheme 26: First synthesis of (±)-BCH-189 (1c) by Belleau et al.
Scheme 27: Enantioselective synthesis of 3TC (1).
Scheme 28: Synthesis of cis-diastereomer 3TC (1) from oxathiolane propionate 44.
Scheme 29: Synthesis of (±)-BCH-189 (1c) via SnCl4-mediated N-glycosylation of 8.
Scheme 30: Synthesis of (+)-BCH-189 (1a) via TMSOTf-mediated N-glycosylation of 20.
Scheme 31: Synthesis of 3TC (1) from oxathiolane precursor 20a.
Scheme 32: Synthesis of 83 via N-glycosylation of 20 with pyrimidine bases.
Scheme 33: Synthesis of 85 via N-glycosylation of 20 with purine bases.
Scheme 34: Synthesis of 86 and 87 via N-glycosylation using TMSOTf and pyrimidines.
Scheme 35: Synthesis of 90 and 91 via N-glycosylation using TMSOTf and purines.
Scheme 36: Synthesis of 3TC (1) via TMSI-mediated N-glycosylation.
Scheme 37: Stereoselective N-glycosylation for the synthesis of 1 by anchimeric assistance of a chiral auxilia...
Scheme 38: Whitehead and co-workers’ approach for the synthesis of 1 via direct N-glycosylation without an act...
Scheme 39: ZrCl4-mediated stereoselective N-glycosylation.
Scheme 40: Plausible reaction mechanism for stereoselective N-glycosylation using ZrCl4.
Scheme 41: Synthesis of enantiomerically pure oxathiolane nucleosides 1 and 2.
Scheme 42: Synthesis of tetrazole analogues of 1,3-oxathiolane nucleosides 97.
Scheme 43: Synthetic approach toward 99 from 1,3-oxathiolane 45 by Camplo et al.
Scheme 44: Synthesis of 100 from oxathiolane phosphonate analogue 46.
Scheme 45: Synthetic approach toward 102 and the corresponding cyclic thianucleoside monophosphate 102a by Cha...
Scheme 46: Synthesis of emtricitabine (2) from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g).
Scheme 47: Synthesis of 1 and 2, respectively, from 56a–d using iodine-mediated N-glycosylation.
Scheme 48: Plausible mechanism for silane- and I2-mediated N-glycosylation.
Scheme 49: Pyridinium triflate-mediated N-glycosylation of 35a.
Scheme 50: Possible pathway for stereoselective N-glycosylation via in situ chelation with a metal ligand.
Scheme 51: Synthesis of novel 1,3-oxathiolane nucleoside 108 from oxathiolane precursor 8 and 3-benzyloxy-2-me...
Scheme 52: Synthesis of 110 using T-705 as a nucleobase and 1,3-oxathiolane derivative 8 via N-glycosylation.
Scheme 53: Synthesis of 1 using an asymmetric leaving group and N-glycosylation with bromine and mesitylene.
Scheme 54: Cytidine deaminase for enzymatic separation of 1c.
Scheme 55: Enzymatic resolution of the monophosphate derivative 116 for the synthesis of (−)-BCH-189 (1) and (...
Scheme 56: Enantioselective resolution by PLE-mediated hydrolysis to obtain FTC (2).
Scheme 57: (+)-Menthyl chloroformate as a resolving agent to separate a racemic mixture 120.
Scheme 58: Separation of racemic mixture 1c by cocrystal 123 formation with (S)-(−)-BINOL.
Double-headed nucleosides: Synthesis and applications
- Vineet Verma,
- Jyotirmoy Maity,
- Vipin K. Maikhuri,
- Ritika Sharma,
- Himal K. Ganguly and
- Ashok K. Prasad
Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98
Graphical Abstract
Figure 1: Double-headed nucleosides. B1 and B2 = nucleobases or heterocyclic/carbocyclic moieties; L = linker....
Scheme 1: Synthesis of 2′-(pyrimidin-1-yl)methyl- or 2′-(purin-9-yl)methyl-substituted double-headed nucleosi...
Scheme 2: Synthesis of double-headed nucleoside 7 having two cytosine moieties.
Scheme 3: Synthesis of double-headed nucleoside 2′-deoxy-2′-C-(2-(thymine-1-yl)ethyl)-uridine (11).
Scheme 4: Double-headed nucleosides 14 and 15 obtained by click reaction.
Scheme 5: Synthesis of the double-headed nucleoside 19.
Scheme 6: Synthesis of the double-headed nucleosides 24 and 25.
Scheme 7: Synthesis of double-headed nucleosides 28 and 29.
Scheme 8: Synthesis of double-headed nucleoside 33.
Scheme 9: Synthesis of double-headed nucleoside 37.
Scheme 10: Synthesis of the double-headed nucleoside 1-(5′-O-(4,4′-dimethoxytrityl)-2′-C-((4-(pyren-1-yl)-1,2,...
Scheme 11: Synthesis of triazole-containing double-headed ribonucleosides 46a–c and 50a–e.
Scheme 12: Synthesis of double-headed nucleosides 54a–g.
Scheme 13: Synthesis of double-headed nucleosides 59 and 60.
Scheme 14: Synthesis of the double-headed nucleosides 63 and 64.
Scheme 15: Synthesis of double-headed nucleosides 66a–c.
Scheme 16: Synthesis of benzoxazole-containing double-headed nucleosides 69 and 71 from 5′-amino-5′-deoxynucle...
Scheme 17: Synthesis of 4′-C-((N6-benzoyladenin-9-yl)methyl)thymidine (75) and 4′-C-((thymin-1-yl)methyl)thymi...
Scheme 18: Synthesis of double-headed nucleosides 5′-(adenine-9-yl)-5′-deoxythymidine (79) and 5′-(adenine-9-y...
Scheme 19: Synthesis of double-headed nucleosides 85–87 via reversed nucleosides methodology.
Scheme 20: Double-headed nucleosides 91 and 92 derived from ω-terminal-acetylenic sugar derivatives 90a,b.
Scheme 21: Synthesis of double-headed nucleosides 96a–g.
Scheme 22: Synthesis of double-headed nucleosides 100 and 103.
Scheme 23: Double-headed nucleosides 104 and 105 with a triazole motif.
Scheme 24: Synthesis of the double-headed nucleosides 107 and 108.
Scheme 25: Synthesis of double-headed nucleoside 110 with additional nucleobase in 5′-(S)-C-position joined th...
Scheme 26: Synthesis of double-headed nucleosides 111–113 with additional nucleobases in the 5′-(S)-C-position...
Scheme 27: Synthesis of double-headed nucleoside 114 by click reaction.
Scheme 28: Synthesis of double-headed nucleosides 118 with an additional nucleobase at the 5′-(S)-C-position.
Scheme 29: Synthesis of bicyclic double-headed nucleoside 122.
Scheme 30: Synthesis of double-headed nucleosides 125a–c derived from 2′-amino-LNA.
Scheme 31: Double-headed nucleoside 127 obtained by click reaction.
Scheme 32: Synthesis of double-headed nucleoside 130.
Scheme 33: Double-headed nucleosides 132a–d and 134a–d synthesized by Sonogashira cross coupling reaction.
Scheme 34: Synthesis of double-headed nucleosides 137 and 138 via Suzuki coupling.
Scheme 35: Synthesis of double-headed nucleosides 140 and 141 via Sonogashira cross coupling reaction.
Scheme 36: Synthesis of double-headed nucleoside 143.
Scheme 37: Synthesis of the double-headed nucleoside 146.
Scheme 38: Synthesis of 5-C-alkynyl-functionalized double-headed nucleosides 151a–d.
Scheme 39: Synthesis of 5-C-triazolyl-functionalized double-headed nucleosides 154a, b.
Scheme 40: Synthesis of double-headed nucleosides 157a–c.
Scheme 41: Synthesis of double-headed nucleoside 159, phosphoramidite 160 and the corresponding nucleotide mon...
Scheme 42: Synthesis of double-headed nucleoside 163, phosphoramidite 164 and the corresponding nucleotide mon...
Scheme 43: Synthesis of double-headed nucleoside 167, phosphoramidite 168, and the corresponding nucleotide mo...
Scheme 44: Synthesis of double-headed nucleoside 171, phosphoramidite 172, and the corresponding nucleotide mo...
Scheme 45: Synthesis of double-headed nucleoside 175, phosphoramidite 176, and the corresponding nucleotide mo...
Scheme 46: Synthesis of double-headed nucleoside 178.
Scheme 47: Synthesis of the double-headed nucleosides 181 and 183.
Scheme 48: Alternative synthesis of the double-headed nucleoside 183.
Scheme 49: Synthesis of double-headed nucleoside 188 through thermal [2 + 3] sydnone–alkyne cycloaddition reac...
Scheme 50: Synthesis of the double-headed nucleosides 190 and 191.
Scheme 51: Synthesis of 1-((5S)-2,3,4-tri-O-acetyl-5-(2,6-dichloropurin-9-yl)-β-ᴅ-xylopyranosyl)uracil (195).
Scheme 52: Synthesis of hexopyranosyl double-headed pyrimidine homonucleosides 200a–c.
Figure 2: 3′-C-Ethynyl-β-ᴅ-allopyranonucleoside derivatives 201a–f.
Scheme 53: Synthesis of 3′-C-(1,4-disubstituted-1,2,3-triazolyl)-double-headed pyranonucleosides 203–207.
Scheme 54: Synthesis of 3′-C-(1,4-disubstituted-1,2,3-triazolyl)-double-headed pyranonucleosides 208 and 209.
Scheme 55: Synthesis of 3′-C-(1,4-disubstituted-1,2,3-triazolyl)-double-headed pyranonucleoside 210.
Scheme 56: Synthesis of double-headed acyclic nucleosides (2S,3R)-1,4-bis(thymine-1-yl)butane-2,3-diol (213a) ...
Scheme 57: Synthesis of double-headed acyclic nucleosides (2R,3S)-1,4-bis(thymine-1-yl)butane-2,3-diol (213c) ...
Scheme 58: Synthesis of double-headed acetylated 1,3,4-oxadiazino[6,5-b]indolium-substituted C-nucleosides 218b...
Scheme 59: Synthesis of double-headed acyclic nucleoside 222.
Scheme 60: Synthesis of functionalized 1,2-bis(1,2,4-triazol-3-yl)ethane-1,2-diols 223a–f.
Scheme 61: Synthesis of acyclic double-headed 1,2,4-triazino[5,6-b]indole C-nucleosides 226–231.
Scheme 62: Synthesis of double-headed 1,3,4-thiadiazoline, 1,3,4-oxadiazoline, and 1,2,4-triazoline acyclo C-n...
Scheme 63: Synthesis of double-headed acyclo C-nucleosides 240–242.
Scheme 64: Synthesis of double-headed acyclo C-nucleoside 246.
Scheme 65: Synthesis of acyclo double-headed nucleoside 250.
Scheme 66: Synthesis of acyclo double-headed nucleoside 253.
Scheme 67: Synthesis of acyclo double-headed nucleosides 259a–d.
Scheme 68: Synthesis of acyclo double-headed nucleoside 261.
Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups
- Xiaoyun Hu,
- Jianxin Guo,
- Cui Wang,
- Rui Zhang and
- Victor Borovkov
Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155
- To develop new efficient stereoselective catalysts for Biginelli-like reactions, a chiral phosphoric acid bearing two hydroxy groups derived from ʟ-tartaric acid was successfully synthesized via highly regioselective transformations of enantiopure 1,1,4,4-tetraphenylbutanetetraol. The obtained
- reported in 2005 by the Akiyama’s group [16]. This work clearly demonstrated the potential of these catalysts in enantioselective transformations. An additional important point of this work was the use of enantiopure tartaric acid as a precursor for the catalyst preparation being a conventional natural
- compound making its application highly attractive from the viewpoint of sustainability and green chemistry. Recently, our group reported an asymmetric Biginelli reaction catalyzed by a new chiral phosphoric acid derived from natural tartaric acid, that yielded a high enantioselectivity (up to 99% ee) [17
Graphical Abstract
Scheme 1: Synthesis of chiral phosphoric acid 3.
Scheme 2: Synthesis of methylated chiral phosphoric acid 7.
Scheme 3: Control experiment with catalyst 7.
Figure 1: A plausible chiral transition-state structure in the Biginelli-like reaction catalyzed by phosphori...
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
- , both academic and commercial laboratories. As a result, two different approaches to the problem emerged where hitherto there had been none (Figure 6). The hydrolysis to an intermediate amine 25 which was then resolved with a derivative of tartaric acid was a solution that emerged from this open source
- approach. Another solution was identified by a sponsored contract research team. This involved a different intermediate 26 which was then, in turn, resolved using tartaric acid itself. A detailed account of the successful resolution process has been published by Matthew Todd and colleagues [173]. This has
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...
Synthesis of disparlure and monachalure enantiomers from 2,3-butanediacetals
- Adam Drop,
- Hubert Wojtasek and
- Bożena Frąckowiak-Wojtasek
Beilstein J. Org. Chem. 2020, 16, 616–620, doi:10.3762/bjoc.16.57
- ensure the required configuration of the asymmetric centers determining the biological activity of this compound. They include the use of naturally occurring chiral substrates, such as ʟ-glutamic acid [13], ʟ-tartaric acid [14][15][16], ᴅ-glucose [17], and sorbitol [18] as starting materials, as well as
- have been described [26][30][31] and we decided to prepare them starting from 2,3-butanediacetal derivatives of ʟ-tartaric acid. This method uses cheap and easily available starting materials, does not require expensive chiral catalysts and offers the possibility of obtaining both enantiomers of
- disparlure and monachalure with high enantiomeric purity. It can also be adapted for preparation of other chiral cis-epoxides. 2,3-Butanediacetals obtained from tartaric acid dimethyl diester contain protected hydroxy groups and two functional groups suitable for the attachment of various substituents. trans
Graphical Abstract
Scheme 1: Retrosynthesis of (+)-disparlure (1), (−)-disparlure (3), (+)-monachalure (2), and (−)-monachalure (...
Scheme 2: Isomerization of trans-2,3-butanediacetals 9–11 to cis-2,3-butanediacetals 12–14.
Scheme 3: Synthesis of diol 17 and its subsequent modifications.
Scheme 4: Synthesis of (+)-disparlure (1) and (+)-monachalure (2).
Scheme 5: Synthesis of (−)-disparlure (3) and (−)-monachalure (4).
A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions
- Munmun Ghosh,
- Valmik S. Shinde and
- Magnus Rueping
Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264
- corresponding alcohol 2 with 14.7% optical yield [21]. Control experiments confirmed that the modified electrodes served as chiral inductors (Scheme 1). In 1982, Fujihira and Osa reported the modification of Raney nickel powder electrodes with optically active tartaric acid and used these electrodes for the
- asymmetric hydrogenation of ketones [22]. They showed that upon reduction with Raney nickel powder electrodes modified with (R,R)-(+)-tartaric acid, 2-hexanone 3 was converted to (S)-(+)-2-hexanol 4 with an average optical purity of 4%, whereas Raney nickel powder electrodes modified with (S,S)-(−)-tartaric
- modified graphite cathode. Asymmetric hydrogenation of ketones using Raney nickel powder electrodes modified with optically active tartaric acid. Asymmetric reduction of prochiral activated olefins with a poly-ʟ-valine-coated graphite cathode. Asymmetric reduction of prochiral carbonyl compounds, oximes
Graphical Abstract
Figure 1: General classification of asymmetric electroorganic reactions.
Scheme 1: Asymmetric reduction of 4-acetylpyridine using a modified graphite cathode.
Scheme 2: Asymmetric hydrogenation of ketones using Raney nickel powder electrodes modified with optically ac...
Scheme 3: Asymmetric reduction of prochiral activated olefins with a poly-ʟ-valine-coated graphite cathode.
Scheme 4: Asymmetric reduction of prochiral carbonyl compounds, oximes and gem-dibromides on a poly-ʟ-valine-...
Scheme 5: Asymmetric hydrogenation of prochiral ketones with poly[RuIII(L)2Cl2]+-modified carbon felt cathode...
Scheme 6: Asymmetric hydrogenation of α-keto esters using chiral polypyrrole film-coated cathode incorporated...
Scheme 7: Quinidine and cinchonidine alkaloid-induced asymmetric electroreduction of acetophenone.
Scheme 8: Asymmetric electroreduction of 4- and 2-acetylpyridines at a mercury cathode in the presence of a c...
Scheme 9: Enantioselective reduction of 4-methylcoumarin in the presence of catalytic yohimbine.
Scheme 10: Cinchonine-induced asymmetric electrocarboxylation of 4-methylpropiophenone.
Scheme 11: Enantioselective hydrogenation of methyl benzoylformate using an alkaloid entrapped silver cathode.
Scheme 12: Alkaloid-induced enantioselective hydrogenation using a Cu nanoparticle cathode.
Scheme 13: Alkaloid-induced enantioselective hydrogenation of aromatic ketones using a bimetallic Pt@Cu cathod...
Scheme 14: Enantioselective reduction of ketones at mercury cathode using N,N'-dimethylquininium tetrafluorobo...
Scheme 15: Asymmetric synthesis of an amino acid using an electrode modified with amino acid oxidase and elect...
Scheme 16: Asymmetric oxidation of p-tolyl methyl sulfide using chemically modified graphite anode.
Scheme 17: Asymmetric oxidation of unsymmetric sulfides using poly(amino acid)-coated electrodes.
Scheme 18: Enantioselective, electocatalytic oxidative coupling on TEMPO-modified graphite felt electrode in t...
Scheme 19: Asymmetric electrocatalytic oxidation of racemic alcohols on a TEMPO-modified graphite felt electro...
Scheme 20: Asymmetric electrocatalytic lactonization of diols on TEMPO-modified graphite felt electrodes.
Scheme 21: Asymmetric electrochemical pinacolization in a chiral solvent.
Scheme 22: Asymmetric electroreduction using a chiral supporting electrolyte.
Scheme 23: Asymmetric anodic oxidation of enol acetates using chiral supporting electrolytes.
Scheme 24: Kinetic resolution of primary amines using a chiral N-oxyl radical mediator.
Scheme 25: Chiral N-oxyl-radical-mediated kinetic resolution of secondary alcohols via electrochemical oxidati...
Scheme 26: Chiral iodoarene-mediated asymmetric electrochemical lactonization.
Scheme 27: Os-catalyzed electrochemical asymmetric dihydroxylation of olefins using the Sharpless ligand and i...
Scheme 28: Asymmetric electrochemical epoxidation of olefins catalyzed by a chiral Mn-salen complex.
Scheme 29: Asymmetric electrooxidation of 1,2-diols, and amino alcohols using a chiral copper catalyst.
Scheme 30: Mechanism of asymmetric electrooxidation of 1,2-diols, and amino alcohols using a chiral copper cat...
Scheme 31: Enantioselective electrocarboxylation catalyzed by an electrogenerated chiral [CoI(salen)]− complex....
Scheme 32: Asymmetric oxidative cross coupling of 2-acylimidazoles with silyl enol ethers.
Scheme 33: Ni-catalyzed asymmetric electroreductive cleavage of allylic β-keto ester 89.
Scheme 34: Asymmetric alkylation using a combination of electrosynthesis and a chiral Ni catalyst.
Scheme 35: Mechanism of asymmetric alkylation using a combination of electrosynthesis and a chiral Ni catalyst....
Scheme 36: Asymmetric epoxidation by electrogenerated percarbonate and persulfate ions in the presence of chir...
Scheme 37: α-Oxyamination of aldehydes via anodic oxidation catalyzed by chiral secondary amines.
Scheme 38: The α-alkylation of aldehydes via anodic oxidation catalyzed by chiral secondary amines.
Scheme 39: Mechanism of α-alkylation of aldehydes via anodic oxidation catalyzed by chiral secondary amines.
Scheme 40: Electrochemical chiral secondary amine-catalyzed intermolecular α-arylation of aldehydes.
Scheme 41: Mechanism of electrochemical chiral secondary amine-catalyzed intermolecular α-arylation of aldehyd...
Scheme 42: Asymmetric cross-dehydrogenative coupling of tertiary amines with simple ketones via an electrochem...
Scheme 43: Electroenzymatic asymmetric reduction using enoate reductase.
Scheme 44: Assymetric reduction using alcohol dehydrogenase as the electrocatalyst.
Scheme 45: Asymmetric electroreduction catalyzed by thermophilic NAD-dependent alcohol dehydrogenase.
Scheme 46: Asymmetric epoxidation of styrene by electrochemical regeneration of flavin-dependent monooxygenase....
Scheme 47: Asymmetric electroreduction using a chloroperoxidase catalyst.
Scheme 48: Asymmetric electrochemical transformation mediated by hydrophobic vitamin B12.
Scheme 49: Diastereoselective cathodic reduction of phenylglyoxalic acids substituted with amines as chiral au...
Scheme 50: Ni-catalyzed asymmetric electroreductive cross coupling of aryl halides with α-chloropropanoic acid...
Scheme 51: Electrochemical Mannich addition of silyloxyfuran to in situ-generated N-acyliminium ions.
Scheme 52: Stereoselective electroreductive homodimerization of cinnamates attached to a camphor-derived chira...
Scheme 53: Diastereoselective electrochemical carboxylation of chiral α-bromocarboxylic acid derivatives.
Scheme 54: Electrocatalytic stereoselective conjugate addition of chiral β-dicarbonyl compounds to methyl viny...
Scheme 55: Stereoselective electrochemical carboxylation of chiral cinnamic acid derivatives under a CO2 atmos...
Scheme 56: Electrochemical diastereoselective α-alkylation of pyrrolidines attached with phosphorus-derived ch...
Scheme 57: Electrogenerated cyanomethyl anion-induced synthesis of chiral cis-β-lactams from amides bearing ch...
Scheme 58: Diastereoselective anodic oxidation followed by intramolecular cyclization of ω-hydroxyl amides bea...
Scheme 59: Electrochemical deprotonation of Ni(II) glycinate containing (S)-BPB as a chiral auxiliary: diaster...
Scheme 60: Enantioselective electroreductive coupling of diaryl ketones with α,β-unsaturated carbonyl compound...
Scheme 61: Asymmetric total synthesis of ropivacaine and its analogues using a electroorganic reaction as a ke...
Scheme 62: Asymmetric total synthesis of (−)-crispine A and its natural enantiomer via anodic cyanation of tet...
Scheme 63: Asymmetric oxidative electrodimerization of cinnamic acid derivatives as key step for the synthesis...
Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids
- Herman O. Sintim,
- Hamad H. Al Mamari,
- Hasanain A. A. Almohseni,
- Younes Fegheh-Hassanpour and
- David M. Hodgson
Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116
- ,S-configuration found in several monoalkylated tartaric acid motif-containing natural products. Keywords: alkylation; cycloaddition; diazoester; epimerisation; tartaric acid; Introduction Since their isolation was reported in the early 1990s [1][2], the squalestatins/zaragozic acids (e.g
- applied in squalestatin syntheses as highlighted above, the monoalkylated tartaric acid motif is also directly present in several natural products, such as hydroxybenzyl-substituted piscidic acid (42) and congeners (fukiic and cimicifugic acids) [50], and the Cephalotaxus alkaloids isoharringtonine (43
- ) and cephalezomine C (44) [51]. In these latter natural products, the monoalkylated tartaric acid residues typically possess 2R,3S stereochemistry (Figure 2); one exception is cephalezomine D [51], which is the 3R-epimer of cephalezomine C (44). Since the chiral (R,R- S,S-) tartrate acetonides undergo
Graphical Abstract
Figure 1: Squalestatin S1/zaragozic acid A (1) and DDSQ (2).
Scheme 1: Carbonyl ylide cycloaddition–rearrangement to the squalestatin core [12,13].
Scheme 2: Tartrate alkylation strategy to cycloaddition substrate.
Scheme 3: Conversion of α-ketoester to α-diazoester.
Scheme 4: Seebach’s tartrate alkylation and rationalisation of stereoselectivity [17-19].
Scheme 5: Tartrate alkylation with a non-activated alkyl iodide.
Scheme 6: Alkylated tartrate to diazoester sequence.
Scheme 7: TES protection approach to the squalestatin core.
Scheme 8: Tartrate acetonide methylation.
Scheme 9: Tartrate alkylation with various alkyl halides.
Scheme 10: Rationalisation of dialkylation observations.
Scheme 11: Tartrate alkylation chemistry with more complex alkyl iodides [12,13].
Figure 2: Natural product examples containing the monoalkylated tartaric acid motif.
Scheme 12: Epimerisation of monoalkylated tartrates.
Synthesis of nonracemic hydroxyglutamic acids
- Dorota G. Piotrowska,
- Iwona E. Głowacka,
- Andrzej E. Wróblewski and
- Liwia Lubowiecka
Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22
- -tartaric acid [104][105] were reduced and the respective hydroxylactams were acetylated to produce acetoxylactams 107a and 107b, necessary intermediates in the next step (Scheme 26) [106][107]. The introduction of the cyano group was accomplished by boron trifluoride-catalyzed reaction with trimethylsilyl
- lower (de 54–64%) with 109b predominating. Nevertheless, efficient separation of the diastereoisomers was achieved for 108a and 109a only and they were deprotected to give enantiomerically pure (2S,3S,4R)-4 and (2R,3S,4R)-4, respectively. Application of D-tartaric acid as a starting material provided
- (2S,3R,4S)-4 and (2R,3R,4S)-4. To secure the (3R,4R) and (3S,4S) configurations in 3,4-hydroxyglutamic acids enantioselective reduction of the carbonyl group of the cyclic imide (3R*,4S*)-110 prepared from meso-tartaric acid [108] needs to be elaborated (Scheme 27) [109]. Low temperature reduction of
Graphical Abstract
Figure 1: Structure of L-glutamic acid.
Figure 2: 3-Hydroxy- (2), 4-hydroxy- (3) and 3,4-dihydroxyglutamic acids (4).
Figure 3: Enantiomers of 3-hydroxyglutamic acid (2).
Scheme 1: Synthesis of (2S,3R)-2 from (R)-Garner's aldehyde. Reagents and conditions: a) MeOCH=CH–CH(OTMS)=CH2...
Scheme 2: Synthesis of (2S,3R)-2 and (2S,3S)-2 from (R)-Garner’s aldehyde. Reagents and conditions: a) H2C=CH...
Scheme 3: Two-carbon homologation of the protected L-serine. Reagents and conditions: a) Fmoc-succinimide, Na2...
Scheme 4: Synthesis of di-tert-butyl ester of (2R,3S)-2 from L-serine. Reagents and conditions: a) PhSO2Cl, K2...
Scheme 5: Synthesis of (2R,3S)-2 from O-benzyl-L-serine. Reagents and conditions: a) (CF3CH2O)2P(O)CH2COOMe, ...
Scheme 6: Synthesis of (2S,3R)-2 employing a one-pot cis-olefination–conjugate addition sequence. Reagents an...
Scheme 7: Synthesis of the orthogonally protected (2S,3R)-2 from a chiral aziridine. Reagents and conditions:...
Scheme 8: Synthesis of N-Boc-protected (2S,3R)-2 from D-phenylglycine. Reagents and conditions: a) BnMgCl, et...
Scheme 9: Synthesis of (2S,3R)-2 employing ketopinic acid as chiral auxiliary. Reagents and conditions: a) Br2...
Scheme 10: Synthesis of dimethyl ester of (2S,3R)-2 employing (1S)-2-exo-methoxyethoxyapocamphane-1-carboxylic...
Scheme 11: Synthesis of N-Boc-protected dimethyl ester of (2S,3R)-2 from (S)-N-(1-phenylethyl)thioacetamide. R...
Scheme 12: Synthesis of N-Boc-protected dimethyl ester of (2S,3R)-2 via Sharpless epoxidation. Reagents and co...
Scheme 13: Synthesis of (2S,3S)-2 from the imide 51. Reagents and conditions: a) NaBH4, MeOH/CH2Cl2; b) Ac2O, ...
Scheme 14: Synthesis of (2R,3S)-2 and (2S,3S)-2 from the acetolactam 55 (PMB = p-methoxybenzyl). Reagents and ...
Scheme 15: Synthesis of (2S,3R)-2 from D-glucose. Reagents and conditions: a) NaClO2, 30% H2O2, NaH2PO4, MeCN;...
Figure 4: Enantiomers of 3-hydroxyglutamic acid (3).
Scheme 16: Synthesis of (4S)-4-hydroxy-L-glutamic acid [(2S,4S)-3] by electrophilic hydroxylation. Reagents an...
Scheme 17: Synthesis of all stereoisomers of 4-hydroxyglutamic acid (3). Reagents and conditions: a) Br2, PBr5...
Scheme 18: Synthesis of the orthogonally protected 4-hydroxyglutamic acid (2S,4S)-73. Reagents and conditions:...
Scheme 19: Synthesis of (2S,4R)-4-acetyloxyglutamic acid as a component of a dipeptide. Reagents and condition...
Scheme 20: Synthesis of N-Boc-protected dimethyl esters of (2S,4R)- and (2S,4S)-3 from (2S,4R)-4-hydroxyprolin...
Scheme 21: Synthesis of orthogonally protected (2S,4S)-3 from (2S,4R)-4-hydroxyproline. Reagents and condition...
Scheme 22: Synthesis of the protected (4R)-4-hydroxy-L-pyroglutamic acid (2S,4R)-87 by electrophilic hydroxyla...
Figure 5: Enantiomers of 3,4-dihydroxy-L-glutamic acid (4).
Scheme 23: Synthesis of (2S,3S,4R)-4 from the epoxypyrrolidinone 88. Reagents and conditions: a) MeOH, THF, KC...
Scheme 24: Synthesis of (2S,3R,4R)-4 from the orthoester 92. Reagents and conditions: a) OsO4, NMO, acetone/wa...
Scheme 25: Synthesis of (2S,3S,4S)-4 from the aziridinolactone 95. Reagents and conditions: a) BnOH, BF3·OEt2,...
Scheme 26: Synthesis of (2S,3S,4R)-4 and (2R,3S,4R)-4 from cyclic imides 106. Reagents and conditions: a) NaBH4...
Scheme 27: Synthesis of (2R,3R,4R)-4 and (2S,3R,4R)-4 from the cyclic meso-imide 110. Reagents and conditions:...
Scheme 28: Synthesis of (2S,3S,4S)-4 from the protected serinal (R)-23. Reagents and conditions: a) Ph3P=CHCOO...
Scheme 29: Synthesis of (2S,3S,4S)-4 from O-benzyl-N-Boc-D-serine. Reagents and conditions: a) ClCOOiBu, TEA, ...
Scheme 30: Synthesis of (2S,3S,4R)-127 by enantioselective conjugate addition and asymmetric dihydroxylation. ...
Figure 6: Structures of selected compounds containing hydroxyglutamic motives (in blue).
A novel and practical asymmetric synthesis of eptazocine hydrobromide
- Ruipeng Li,
- Zhenren Liu,
- Liang Chen,
- Jing Pan,
- Kuaile Lin and
- Weicheng Zhou
Beilstein J. Org. Chem. 2018, 14, 2340–2347, doi:10.3762/bjoc.14.209
- water (50 mL) and saturated saline solution (50 mL). The organic layers were dried, filtered and concentrated to yield a crude oil. The crude oil was purified through salt formation with tartaric acid (3.96 g, 0.026 mol) in ethyl alcohol (60 mL) and basification to afford 13 as colorless oil (4.49 g
Graphical Abstract
Scheme 1: Commercial process for the synthesis of 1.
Scheme 2: Previous work about asymmetric synthesis of I-13a.
Scheme 3: Asymmetric synthesis of 1.
Scheme 4: The second strategy for the asymmetric synthesis of 1.
Enantioselective phase-transfer catalyzed alkylation of 1-methyl-7-methoxy-2-tetralone: an effective route to dezocine
- Ruipeng Li,
- Zhenren Liu,
- Liang Chen,
- Jing Pan and
- Weicheng Zhou
Beilstein J. Org. Chem. 2018, 14, 1421–1427, doi:10.3762/bjoc.14.119
- separated by two times of resolution with L-tartaric acid and D-tartaric acid (Scheme 1). Phase-transfer asymmetric catalysis with cinchona alkaloid-derived quaternary ammonium compounds has become one of the topics in stereoselective synthesis in both industry and academia [6][7][8][9]. It was reported [10
Graphical Abstract
Scheme 1: Synthesis of dezocine by resolution.
Scheme 2: Synthesis of catalysts C1–C17.
Scheme 3: The proposed catalytic mechanism of stereoselective alkylation.
A survey of chiral hypervalent iodine reagents in asymmetric synthesis
- Soumen Ghosh,
- Suman Pradhan and
- Indranil Chatterjee
Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107
- derivatives of L-tartaric acid anhydrides in 1986. A promising asymmetric induction was achieved for the oxidation of sulfides 23 to sulfoxides 24. This marked the beginning of an era of asymmetric oxidation of sulfides. However, the presence of C2 symmetry in the chiral unit is essential to obtain decent
- enantioselectivity [24]. Later, Kita et al. used chiral tartaric acid derivatives to synthesize chiral I(V) reagents 2 from PhIO2. This represented the first example of the catalytic use of chiral hypervalent reagents in the oxidation of sulfides to sulfoxides with decent enantioselectivities (ees, Scheme 2a). The
Graphical Abstract
Scheme 1: An overview of different chiral iodine reagents or precursors thereof.
Scheme 2: Asymmetric oxidation of sulfides by chiral hypervalent iodine reagents.
Scheme 3: Oxidative dearomatization of naphthol derivatives by Kita et al.
Scheme 4: [4 + 2] Diels–Alder dimerization reported by Birman et al.
Scheme 5: m-CPBA guided catalytic oxidative naphthol dearomatization.
Scheme 6: Oxidative dearomatization of phenolic derivatives by Ishihara et al.
Scheme 7: Oxidative spirocyclization applying precatalyst 11 developed by Ciufolini et al.
Scheme 8: Asymmetric hydroxylative dearomatization.
Scheme 9: Enantioselective oxylactonization reported by Fujita et al.
Scheme 10: Dioxytosylation of styrene (47) by Wirth et al.
Scheme 11: Oxyarylation and aminoarylation of alkenes.
Scheme 12: Asymmetric diamination of alkenes.
Scheme 13: Stereoselective oxyamination of alkenes reported by Wirth et al.
Scheme 14: Enantioselective and regioselective aminofluorination by Nevado et al.
Scheme 15: Fluorinated difunctionalization reported by Jacobsen et al.
Scheme 16: Aryl rearrangement reported by Wirth et al.
Scheme 17: α-Arylation of β-ketoesters.
Scheme 18: Asymmetric α-oxytosylation of carbonyls.
Scheme 19: Asymmetric α-oxygenation and α-amination of carbonyls reported by Wirth et al.
Scheme 20: Asymmetric α-functionalization of ketophenols using chiral quaternary ammonium (hypo)iodite salt re...
Scheme 21: Oxidative Intramolecular coupling by Gong et al.
Scheme 22: α-Sulfonyl and α-phosphoryl oxylation of ketones reported by Masson et al.
Scheme 23: α-Fluorination of β-keto esters.
Scheme 24: Alkynylation of β-ketoesters and amides catalyzed by phase-transfer catalyst.
Scheme 25: Alkynylation of β-ketoesters and dearomative alkynylation of phenols.
A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine
- Bettina Riedl and
- Walther Schmid
Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71
- pivotal role in cell–cell interaction and receptor induced cell signaling. Herein, we present a synthetic route in which two of the four stereogenic centers present in the target compound are derived from enantiopure tartaric acid being selectively converted to epoxy alcohols. The key step is the Pd
- the missing isomers of 2-amino sugars, as well as new derivatives are still highly desired. The here presented flexible approach towards GalNAc and IdoNAc from epoxythreitol 5 is a first step to answer this request. These molecules can be approached from tartaric acid (3), which already provides two
- A synthetic route was developed starting with both the D- and the L-epoxythreitol 5a and 5b. These isomers have been synthesized from D- (3a) and L-tartaric acid (3b), respectively, through an approach that has been published earlier by Iida et al. (Scheme 1) [16]. Here, tartaric acid predefines the
Graphical Abstract
Figure 1: Four possible isomers reachable through the presented approach.
Scheme 1: Sharpless epoxidation to gain D-galacto- 5a and L-galacto-configured epoxythreitol 5b.
Scheme 2: Reagents and conditions: a) i) (COCl)2, DMSO, Et3N, DCM, ii) triethyl phosphonoacetate, NaH, DCM; b...
Scheme 3: Proposed mechanism of the Pd-catalyzed azide substitution of 6a in protic solvent.
Scheme 4: Approach towards peracetylated D-IdoNAc 2c, reactions and conditions: a) Ti(OiPr)4, t-BuOOH, D-DET,...
Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres
- Myriam Drouin and
- Jean-François Paquin
Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262
- HWE olefination (Scheme 5). The (E)-monofluoroalkene was thus obtained in an excellent selectivity using n-butyllithium in tert-butyl methyl ether. The resulting ester 21 was reduced using lithium aluminum hydride, and treatment with tartaric acid deprotected the OBO, thus providing the free triol 22
Graphical Abstract
Figure 1: Selected amide bond isosteres.
Figure 2: Monofluoroalkene as an amide bond isostere.
Scheme 1: Synthesis of Cbz-Gly-ψ[(Z)-CF=CH]-Gly using a HWE olefination by Sano and co-workers.
Scheme 2: Synthesis of Phth-Gly-ψ[CF=CH]-Gly using the Julia–Kocienski olefination by Lequeux and co-workers.
Scheme 3: Synthesis of Boc-Nva-ψ[(Z)-CF=CH]-Gly by Taguchi and co-workers.
Figure 3: Mutant tripeptide containing two different peptide bond isosteres.
Scheme 4: Chromium-mediated synthesis of Boc-Ser(PMB)-ψ[(Z)-CF=CH]-Gly-OMe by Konno and co-workers.
Scheme 5: Synthesis of Cbz-Gly-ψ[(E)-CF=C]-Pro by Sano and co-workers.
Scheme 6: Synthesis of Cbz-Gly-ψ[(Z)-CF=C]-Pro by Sano and co-workers.
Scheme 7: Stereoselective synthesis of Fmoc-Gly-ψ[(Z)-CF=CH]-Phe by Pannecoucke and co-workers.
Scheme 8: Ring-closure metathesis to prepare Gly-ψ[(E)-CF=CH]-Phg by Couve-Bonnaire and co-workers.
Scheme 9: Stereoselective synthesis of Fmoc-Gly-ψ[(Z)-CF=CH]-Phe by Dory and co-workers.
Scheme 10: Diastereoselective addition of Grignard reagents to sulfinylamines derived from α-fluoroenals by Pa...
Scheme 11: NHC-mediated synthesis of monofluoroalkenes by Otaka and co-workers.
Scheme 12: Stereoselective synthesis of Boc-Tyr-ψ[(Z)-CF=CH]-Gly by Altman and co-workers.
Scheme 13: Synthesis of the tripeptide Boc-Asp(OBn)-Pro-ψ[(Z)-CF=CH)-Val-CH2OH by Miller and co-workers.
Scheme 14: Copper-catalyzed synthesis of monofluoralkenes by Taguchi and co-workers.
Scheme 15: One-pot intramolecular redox reaction to access amide-type isosteres by Otaka and co-workers.
Scheme 16: Copper-mediated reduction, transmetalation and asymmetric alkylation by Fujii and co-workers.
Scheme 17: Synthesis of (E)-monofluoroalkene-based dipeptide isostere by Fujii and co-workers.
Scheme 18: Diastereoselective synthesis of MeOCO-Val-ψ[(Z)-CF=C]-Pro isostere by Chang and co-workers.
Scheme 19: Asymmetric synthesis of Fmoc-Ala-ψ[(Z)-CF=C]-Pro by Pannecoucke and co-workers.
Scheme 20: Synthesis of Fmoc-Val-ψ[(E)-CF=C]-Pro by Pannecoucke and co-workers.
Figure 4: BMS-790052 and its fluorinated analogue.
Figure 5: Bioactivities of pentapeptide analogues based on the relative maximum agonistic activity at 10 nM o...
Figure 6: Structures and affinities of the Leu-enkephalin and its fluorinated analogue. The affinity towards ...
Figure 7: Activation of the opioid receptor DOPr by Leu-enkephaline and a fluorinated analogue.
Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles
- Johannes Schörgenhumer,
- Maximilian Tiffner and
- Mario Waser
Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170
- ][30]. Alternative approaches by utilizing chiral backbones like, e.g., tartaric acid, biphenyls, or tricyclic ammonium salts were also heavily investigated [31][32][33][34][35], thus leading to an enormous recent progress in the field with respect to catalyst design and the development of new
Graphical Abstract
Scheme 1: Generally accepted ion-pairing mechanism between the chiral cation Q+ of a PTC and an enolate and s...
Scheme 2: Reported asymmetric α-fluorination of β-ketoesters 1 using different chiral PTCs.
Scheme 3: Asymmetric α-fluorination of benzofuranones 4 with phosphonium salt PTC F1.
Scheme 4: Asymmetric α-fluorination of 1 with chiral phosphate-based catalysts.
Scheme 5: Anionic PTC-catalysed α-fluorination of enamines 7 and ketones 10.
Scheme 6: PTC-catalysed α-chlorination reactions of β-ketoesters 1.
Scheme 7: Shioiri’s seminal report of the asymmetric α-hydroxylation of 15 with chiral ammonium salt PTCs.
Scheme 8: Asymmetric ammonium salt-catalysed α-hydroxylation using oxygen together with a P(III)-based reduct...
Scheme 9: Asymmetric ammonium salt-catalysed α-photooxygenations.
Scheme 10: Asymmetric ammonium salt-catalysed α-hydroxylations using organic oxygen-transfer reagents.
Scheme 11: Asymmetric triazolium salt-catalysed α-hydroxylation with in situ generated peroxy imidic acid 24.
Scheme 12: Phase-transfer-catalysed dearomatization of phenols and naphthols.
Scheme 13: Ishihara’s ammonium salt-catalysed oxidative cycloetherification.
Scheme 14: Chiral phase-transfer-catalysed α-sulfanylation reactions.
Scheme 15: Chiral phase-transfer-catalysed α-trifluoromethylthiolation of β-ketoesters 1.
Scheme 16: Chiral phase-transfer-catalysed α-amination of β-ketoesters 1 using diazocarboxylates 38.
Scheme 17: Asymmetric α-fluorination of benzofuranones 4 using diazocarboxylates 38 in the presence of phospho...
Scheme 18: Anionic phase-transfer-catalysed α-amination of β-ketoesters 1 with aryldiazonium salts 41.
Scheme 19: Triazolium salt L-catalysed α-amination of different prochiral nucleophiles with in situ activated ...
Scheme 20: Phase-transfer-catalysed Neber rearrangement.
From chemical metabolism to life: the origin of the genetic coding process
- Antoine Danchin
Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111
- shapes of molecules [37]. After discovering that only one 3D form of tartaric acid was present in the lees of wine Pasteur claimed “La dissymétrie, c’est la vie” (dissymmetry, this is life). Indeed, the carbon-based molecules of life are restricted to a subset of compounds with identical chemical
Graphical Abstract
Figure 1: Selective surface metabolism. Prebiotic carbon-based molecules accumulated in a neutral or slightly...
Figure 2: Building up membranes, peptides and co-enzymes. Thioester-based metabolism resulted in the synthesi...
Figure 3: The RNA metabolism world. Among molecules built up by a swinging-arm thioester are pyrimidines coup...
Copper-catalyzed asymmetric sp3 C–H arylation of tetrahydroisoquinoline mediated by a visible light photoredox catalyst
- Pierre Querard,
- Inna Perepichka,
- Eli Zysman-Colman and
- Chao-Jun Li
Beilstein J. Org. Chem. 2016, 12, 2636–2643, doi:10.3762/bjoc.12.260
- of THIQs with arylboronic esters via asymmetric organocatalysis methodology [25][28]. The use of chiral tartaric acid derivatives, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and high temperature (70 °C) were found to be the optimal conditions to obtain the desired arylated product with
Graphical Abstract
Scheme 1: Design light-mediated arylation of THIQs.
Figure 1: Reaction scope. Reaction conditions: THIQs (0.10 mmol), arylboronic acid (0.30 mmol), TBHP (0.2 mmo...
Scheme 2: Evaluation of chiral ligands.
Scheme 3: Proposed reaction mechanism.
A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug
- Wiesława Perlikowska,
- Remigiusz Żurawiński and
- Marian Mikołajczyk
Beilstein J. Org. Chem. 2016, 12, 2234–2239, doi:10.3762/bjoc.12.215
- be prepared from optically inactive meso-tartaric acid through a two-step reaction sequence. It involves a complete desymmetrization during an acid-catalyzed reaction with (+)-camphor and methyl orthoformate and the subsequent treatment of the formed methyl diester with α-phosphonate carbanion
Graphical Abstract
Figure 1: Structure of rosaprostol (1) and numbering system.
Figure 2: The structures of stereoisomers of rosaprostol (1).
Scheme 1: Synthesis of stereoisomeric rosaprostols 1a and 1b from (−)-2a.
Scheme 2: Synthesis of racemic rosaprostol (±-1).
Scheme 3: Resolution of racemic cyclopentanone 3. Reagents and conditions: (a) Al2O3, SiO2, MS 5 Å, DCM, rt, ...
Scheme 4: Synthesis of rosaprostol stereoisomers 1a and 1c. Reagents and conditions: (a) KOH/Al2O3, OHC(CH2)5...
Scheme 5: Conversion of methyl ester (+)-6 into rosaprostol (−)-1a. Reagents and conditions: (a) L-Selectride...
Scheme 6: Synthesis of rosaprostol stereoisomers 1b and 1d. Reagents and conditions: (a) CH2N2, Et2O, −30 °C;...
Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes
- Lucie Brulíková,
- Aidan Harrison,
- Marvin J. Miller and
- Jan Hlaváč
Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184
- representative examples are depicted in Scheme 43. Approach based on the activation of a moderately reactive arylnitroso dienophile; coordination of the diene: The Inomata group studied a different system utilizing the coordination of a hydroxylated diene to a tartaric acid ester [150][151][152]. When they
- enantioselectivity encouraged the Inomata group to further investigate the reaction [152]. Their investigation of enantioselective hetero-Diels–Alder reactions resulted in an enantioselectivity of up to 92% ee, when nitrosobenzene and a dienol were reacted in the presence of tartaric acid ester as a chiral auxiliary
Graphical Abstract
Scheme 1: Nitroso hetero-Diels–Alder reaction.
Scheme 2: The hetero-Diels–Alder reaction between thebaine (4) and an acylnitroso dienophile 5.
Figure 1: Examples of nitroso dienophiles frequently used in hetero-Diels–Alder reaction studies.
Scheme 3: Synthesis of arylnitroso species by substitution of a trifluoroborate group [36].
Scheme 4: Synthesis of arylnitroso compounds by amine oxidation.
Scheme 5: Synthesis of arylnitroso compounds by hydroxylamine oxidation.
Scheme 6: Synthesis of chloronitroso compounds by the treatment of a nitronate anion with oxalyl chloride.
Scheme 7: Non-oxidative routes to acylnitroso species.
Figure 2: RB3LYP/6-31G* computed energies (in kcal·mol−1) and bond lengths for exo and endo-transition states...
Scheme 8: Hetero-Diels–Alder cycloadditions of diene 28 and nitroso dienophiles 29.
Figure 3: Relative reactivity (ΔE#) and regioselectivity (Δ) for hetero-Diels–Alder of 28 and nitroso dienoph...
Scheme 9: Reaction of chiral 1-phosphono-1,3-butadiene 31 with nitroso dienophiles 32.
Scheme 10: Hetero-Diels–Alder reactions of hydroxamic acids 35 with various dienes 37.
Scheme 11: General regioselectivity of the nitroso hetero-Diels–Alder reaction observed with unsymmetrical die...
Scheme 12: Effect of the nitroso species on the regioselectivity for weakly directing 2-substituted dienes.
Scheme 13: Regioselectivity of 1,4-disubstituted dienes 51.
Scheme 14: Nitroso hetero-Diels–Alder reaction between Boc-nitroso compound 54 and dienes 55.
Scheme 15: Nitroso hetero-Diels–Alder reaction between Wightman reagent 58 and dienes 59.
Scheme 16: Regioselective reaction of 3-dienyl-2-azetidinones 62 with nitrosobenzene (47).
Scheme 17: The regioselective reaction of 1,3-butadienes 65 with various nitroso heterodienophiles 66.
Scheme 18: Catalysis of the nitroso hetero-Diels–Alder reaction by vanadium in the presence of the oxidant CHP...
Figure 4: 1,2-Oxazines synthesized in solution with moderate to high regioselectivity, showing the favored re...
Figure 5: 1,2-Oxazines synthesized in the solid phase with moderate to high regioselectivity, showing the fav...
Scheme 19: Regioselectivity of solution-phase nitroso hetero-Diels–Alder reaction with acyl and aryl nitroso d...
Scheme 20: Favored regioisomeric outcome for the solution and solid-phase reactions, giving hetero-Diels–Alder...
Figure 6: Favored regioisomers and regioisomeric ratios for 1,2-oxazines synthesized in solid phase (91, 93, ...
Scheme 21: Regiocontrol of the reaction between 3-dienyl-2-azetidinones and nitrosobenzene due to change in a ...
Scheme 22: Regiocontrol of the reaction between diene 111 and 2-methyl-6-nitrosopyridine (112) due to metal co...
Scheme 23: Asymmetric hetero-Diels–Alder reactions reported by Vasella [56].
Scheme 24: Asymmetric hetero-Diels–Alder reaction of cyclohexa-1,3-diene (120) with acylnitroso dienophile 119....
Scheme 25: Asymmetric induction with L-proline derivatives 124–126.
Scheme 26: Asymmetric cycloaddition of the acylnitroso compound 136 to diene 135.
Scheme 27: Asymmetric induction with arylmenthol-based nitroso dienophiles 142.
Scheme 28: Cycloaddition of silyloxycyclohexadiene 145 to the acylnitroso dienophile derived from (+)-camphors...
Scheme 29: Asymmetric reaction of O-isopropylidene-protected cis-cyclohexa-3,5-diene-1,2-diol 147 with mannofu...
Scheme 30: Synthesis of synthon 152 from 2-methoxyphenol 150 and chiral auxiliary 151.
Scheme 31: Asymmetric nitroso hetero-Diels–Alder reaction with Wightman chloronitroso reagent 58.
Scheme 32: Asymmetric 1,2-oxazine synthesis using chiral cyclic diene 157 and the application of this reaction...
Scheme 33: Asymmetric 1,2-oxazine synthesis using a chiral diene reported by Jones et al. [75]. aRegioisomeric rat...
Scheme 34: The nitroso hetero-Diels–Alder reaction of acyclic oxazolidine-substituted diene 170 and chiral 1-s...
Scheme 35: The nitroso hetero-Diels–Alder reaction of acyclic lactam-substituted diene 176 with various acylni...
Scheme 36: The hetero-Diels–Alder reaction of acylnitroso dienophile.
Scheme 37: The hetero-Diels–Alder reaction of arylnitroso dienophiles using Lewis acids.
Scheme 38: Asymmetric hetero-Diels–Alder reactions of chiral alkyl N-dienylpyroglutamates.
Scheme 39: Catalytic asymmetric arylnitroso reaction between mono-substituted 1,3-cyclohexadiene 196 and disub...
Figure 7: Plausible chelate intermediate complexes formed during the hetero-Diels–Alder reaction to give 1,2-...
Scheme 40: Catalytic asymmetric nitroso hetero-Diels–Alder between cyclic dienes and 2-nitrosopyridine.
Scheme 41: The reason for the increased enantioselectivity of stereoisomer 212 compared with stereoisomer 213.
Scheme 42: The copper-catalyzed nitroso hetero-Diels–Alder reaction of 6-methyl-2-nitrosopyridine (199) with p...
Scheme 43: Asymmetric nitroso hetero-Diels–Alder reaction of nitrosoarenes with dienylcarbamates catalyzed by ...
Scheme 44: The enantioselective hetero-Diels–Alder reaction between nitrosobenzene and (E)-2,4-pentadien-1-ol (...
Scheme 45: Asymmetric nitroso hetero-Diels–Alder reaction using tartaric acid ester chelation of the diene and...
Self and directed assembly: people and molecules
- Tony D. James
Beilstein J. Org. Chem. 2016, 12, 391–405, doi:10.3762/bjoc.12.42
- formed very strongly complexes with tartaric acid [60]. This paper made us realise that our chiral binol boronic acid 8 should be able to discriminate the enantiomers of tartaric acid and also bind strongly with other sugar acids. Therefore, with Jianzhang Zhao an outstanding Postdoctoral Research Fellow
- in my group and currently a Professor at Dalian University of Technology, we decided to investigate the properties of the enantiomerically pure forms of the receptor with chiral tartaric acid and other sugar acids. It turned out that the chiral system 8 (R or S) was very good at differentiating the
- enantiomers of tartaric acid and also bound bind strongly with other sugar acids [61] (Figure 9). While, we were very happy with these results, we realised that the system could be improved by changing the fluorophore from binol, to a much better fluorophore such as anthracene. Therefore, we combined the
Graphical Abstract
Scheme 1: Reaction of trimethylsilyl cyanide with tricarbonyl (η5-cyclohexadienyl)iron(1+) salts. Reproduced ...
Figure 1: (a) Supramolecular pore formers. Reproduced with permission from [6]. Copyright 1990 Elsevier. (b) Uni...
Figure 2: An intelligent liquid crystal to read out saccharide structure as a color-change. Picture provided ...
Scheme 2: Polymeric boronic acid receptor units developed by Wulff. Reproduced from [16]. Copyright 1982 Internat...
Figure 3: Fluorescence photoinduced electron transfer (PET) pH sensor developed by A. P. De Silva.
Figure 4: Fluorescence PET sensor for saccharides.
Figure 5: (a) Glucose selective PET system. (b) Chiral discriminating PET system.
Figure 6: (a) Fluorescence photoinduced electron transfer (PET) cation sensors developed by A. P. De Silva. (...
Figure 7: (a) Pyrene diboronic acids (n = 3–8). (b) Pyrene monoboronic acid. (c) Block chart showing the rela...
Figure 8: Glysure Continuous Intravascular Glucose Monitoring (CIGM) System. Image provided by Nicholas P. Ba...
Figure 9: Chiral discrimination of D- and L-tartaric acid by (R)-8 at pH 5.6. [(R)-8] = 5.0 × 10−6 mol dm−3, ...
Figure 10: Chiral discriminating sensor (relative stereochemistry shown) constructed using a good fluorophore ...
Figure 11: Fluorescence emission intensity-pH profile of: (a) Sensor 15: 1.0 × 10−6 mol dm−3 (λex 370 nm, λem ...
Figure 12: Modular chiral discriminating d-PET systems (relative stereochemistry shown).
Figure 13: With Matthew Davidson and Steven Bull during “World Cup” lecture tour of Japan in 2002. (Left) Priv...
Figure 14: Preparation of chiral boron reagent and use as catalyst for aza-Diels–Alder reactions.
Figure 15: Chiral three component self-assembling system.
Recent advances in copper-catalyzed asymmetric coupling reactions
- Fengtao Zhou and
- Qian Cai
Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280
- stereogenic centers, derived from tartaric acid, giving the product as a single isomer in good yield (Scheme 11). Sugimura et al. [31] expanded this method by introducing chiral 1,3-diol-derived tethers into the substrates, delivering the corresponding coupling products in excellent diastereoselectivity
Graphical Abstract
Scheme 1: Copper-catalyzed asymmetric preparation of biaryl diacids by Ullmann coupling.
Scheme 2: Intramolecular biaryl coupling of bis(iodotrimethoxybenzoyl)hexopyranose derivatives.
Scheme 3: Preparation of 3,3’-disubstituted MeO-BIPHEP derivatives.
Scheme 4: Enantioselective synthesis of trans-4,5,9,10-tetrahydroxy-9,10-dihydrophenanthrene.
Scheme 5: Copper-catalyzed coupling of oxazoline-substituted aromatics to afford biaryl products with high di...
Scheme 6: Total synthesis of O-permethyl-tellimagrandin I.
Scheme 7: Total synthesis of (+)-gossypol.
Scheme 8: Total synthesis of (−)-mastigophorene A.
Scheme 9: Total synthesis of isokotanin.
Scheme 10: Synthesis of dimethyl[7]thiaheterohelicenes.
Scheme 11: Intramolecular coupling with chiral ortho-substituents.
Scheme 12: Chiral 1,3-diol-derived tethers in the diastereoselective synthesis of biaryl compounds.
Scheme 13: Synthesis of chiral unsymmetrically substituted biaryl compounds.
Scheme 14: Atroposelective synthesis of biaryl ligands and natural products by using a chiral diether linker.
Scheme 15: Enantioselective arylation reactions of 2-methylacetoacetates.
Scheme 16: Asymmetric aryl C–N coupling reactions following a desymmetrization strategy.
Scheme 17: Construction of cyano-bearing all-carbon quaternary stereocenters.
Scheme 18: An unexpected inversion of the enantioselectivity in the asymmetric C–N coupling reactions using ch...
Scheme 19: Differentiation of two nucleophilic amide groups.
Scheme 20: Synthesis of spirobilactams through a double N-arylation reaction.
Scheme 21: Asymmetric N-arylation through kinetic resolution.
Scheme 22: Formation of cyano-substituted quaternary stereocenters through kinetic resolution.
Scheme 23: Copper-catalyzed intramolecular desymmetric aryl C–O coupling.
Scheme 24: Transition metal-catalyzed allylic substitutions.
Scheme 25: Copper-catalyzed asymmetric allylic substitution of allyl phosphates.
Scheme 26: Allylic substitution of allyl phosphates with allenylboronates.
Scheme 27: Allylic substitution of allyl phosphates with vinylboron.
Scheme 28: Allylic substitution of allyl phosphates with vinylboron.
Scheme 29: Construction of quaternary stereogenic carbon centers through enantioselective allylic cross-coupli...
Scheme 30: Cu-catalyzed enantioselective allyl–allyl cross-coupling.
Scheme 31: Cu-catalyzed enantioselective allylic substitutions with silylboronates.
Scheme 32: Asymmetric allylic substitution of allyl phosphates with silylboronates.
Scheme 33: Stereoconvergent synthesis of chiral allylboronates.
Scheme 34: Enantioselective allylic substitutions with diboronates.
Scheme 35: Enantioselective allylic alkylations of terminal alkynes.
Design and synthesis of hybrid cyclophanes containing thiophene and indole units via Grignard reaction, Fischer indolization and ring-closing metathesis as key steps
- Sambasivarao Kotha,
- Ajay Kumar Chinnam and
- Mukesh E. Shirbhate
Beilstein J. Org. Chem. 2015, 11, 1514–1519, doi:10.3762/bjoc.11.165
- of a mixture of L-(+)-tartaric acid/N,N′-dimethylurea (30:70) was heated to 70 °C to obtain a clear melt. To this melt, 2 mmol of N-methyl-N-phenylhydrazine and 1 mmol of diketone were added at 70 °C. After completion of the reaction (TLC monitoring by mini work up), the reaction mixture was quenched
Graphical Abstract
Figure 1: Retrosynthetic approach to hybrid cyclophane derivative 1.
Scheme 1: Attempted synthesis of thiophenophane derivative 2.
Scheme 2: Synthesis of hybrid cyclophane 1.
Figure 2: The molecular crystal structure of 1 with 50% probability [41].
Scheme 3: Attempted synthesis of thiophenophane derivative 2a.
Scheme 4: Synthesis of cyclophane 1a with a thiophene and an indole moiety.
