ABSTRACT
This review summarizes recently established methodologies developed for the enantioselective and diastereoselective synthesis of chiral 1,3-oxazines. These compounds are of interest as advanced synthetic intermediates in the total synthesis of structurally complex and biologically active polyhydroxylated alkaloids such as (+)-1-deoxynojirimycin, (-)-anisomycin, (+)-castanospermine, (+)-casuarine, (-)-conduramine F-1, (-)-sphingofungin B, Neu5Ac methyl ester, and other natural products. The devised synthetic approach aims to offer a direct, efficient, and adaptable method for obtaining both pure enantiomers and pure diastereomers. It revolves around utilizing chiral building blocks like syn,syn-, syn,syn,anti-, syn,anti-, syn,anti,syn-, anti,syn-, anti,syn,syn-, and anti,syn,anti-oxazines. By integrating oxazine chemistry with established and innovative transformations, this approach enabled the synthesis of 30 polyhydroxylated amines across various studies conducted between 2007 and 2022.
ABSTRACT
Concise and stereocontrolled total syntheses of (+)-castanospermine and N-acetylneuraminic acid methyl ester were achieved from diastereomerically enriched anti, syn, syn-1,3-oxazine and anti, syn, anti-1,3-oxazine, respectively. The key step in this strategy was the stereoselective BF3·OEt2-mediated allylation.
ABSTRACT
This paper describes the stereoselective total syntheses of (+)-1-deoxygalactonojirimycin and (-)-1-deoxygulonojirimycin via new chiral building blocks syn,anti,syn-oxazine 11a and syn,syn,anti-oxazine 13a. These were accomplished in four steps in 44.1 and 33.7% overall yields, respectively. These chirons were derived from the stereoselective addition of a nucleophile to the corresponding aldehydes of syn,anti-oxazine 10 and syn,syn-oxazine 12. Furthermore, this paper describes the stereochemical analysis of three types of chiral 1,3-oxazines; anti,syn-, syn,anti-, and syn,syn-oxazines using the NOESY technique.
ABSTRACT
Concise and stereocontrolled syntheses of (+)-hyacinthacine A2 and sphingofungin B were achieved via a diastereomerically enriched oxazine intermediate. The key strategies include palladium(0)-catalyzed intramolecular oxazine formation and diastereoselective nucleophilic addition to an aldehyde. (+)-Hyacinthacine A2 was synthesized in 13 steps and 10.2% overall yield and the synthesis of sphingofungin B proceeded in a linear sequence over 15 steps and 6.9% overall yield from (R)-methyl 2-benzamido-3-((tert-butyldimethylsilyl)oxy)propanoate.
Subject(s)
Biological Products/chemical synthesis , Oxazines/chemistry , Pyrrolizidine Alkaloids/chemical synthesis , Amino Acids/chemical synthesis , Amino Acids/chemistry , Aspergillus fumigatus/chemistry , Biological Products/chemistry , Fatty Acids, Unsaturated/chemical synthesis , Fatty Acids, Unsaturated/chemistry , Liliaceae/chemistry , Oxazines/chemical synthesis , Palladium/chemistry , Pyrrolizidine Alkaloids/chemistry , StereoisomerismABSTRACT
We report a new asymmetric synthetic method for (-)-swainsonine utilizing a chiral oxazoline precursor. The key features in this strategy are the diastereoselective oxazoline formation reaction catalyzed by palladium(0), diasteroselective dihydroxylation, and the stereocontrolled allylation reaction with TiCl(4).
Subject(s)
Swainsonine/chemical synthesis , Antineoplastic Agents, Phytogenic/chemical synthesis , Antineoplastic Agents, Phytogenic/chemistry , Oxazoles/chemistry , Stereoisomerism , Substrate Specificity , Swainsonine/chemistryABSTRACT
A concise, stereocontrolled synthesis of (+)-polyoxamic acid was achieved. Starting from trans-oxazoline as a chiral building block, the key step involves diastereoselective oxazine formation catalyzed by palladium(0).
Subject(s)
Amino Acids/chemical synthesis , Oxazines/chemical synthesis , Sugar Acids/chemical synthesis , Amino Acids/chemistry , Molecular Conformation , Oxazines/chemistry , Stereoisomerism , Sugar Acids/chemistryABSTRACT
The enantioselective total synthesis of (-)-anisomycin, a potent antibiotic agent, has been achieved. The key steps are a Pd(0)-catalyzed stereoselective intramolecular oxazine formation from d-tyrosine and pyrrolidine formation by catalytic hydrogenation of the oxazine.
Subject(s)
Anisomycin/chemical synthesis , Anti-Bacterial Agents/chemical synthesis , Oxazines/chemical synthesis , Palladium/chemistry , Anisomycin/chemistry , Anti-Bacterial Agents/chemistry , Catalysis , Molecular Structure , Oxazines/chemistry , Pyrrolidines/chemistry , Tyrosine/chemistryABSTRACT
In this study, we explored a convenient and concise route for synthesis of D-erythro-sphingosine 1 from commercially available and cheap L-serine. The key steps are simple preparation of amino ketone 5 from Weinreb amide 3 and high diastereoselective reduction of amino ketone 5 to give the natural erythro-(anti-) isomer.
Subject(s)
Protein Kinase C/antagonists & inhibitors , Protein Kinase Inhibitors/chemical synthesis , Sphingosine/analogs & derivatives , Technology, Pharmaceutical/methods , Amides/chemical synthesis , Chemistry, Pharmaceutical , Ketones/chemical synthesis , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Structure , Oxidation-Reduction , Protein Kinase Inhibitors/pharmacology , Serine/chemistry , Spectroscopy, Fourier Transform Infrared , Sphingosine/chemical synthesis , Sphingosine/pharmacology , StereoisomerismABSTRACT
In this study, we explored a convenient and concise route for synthesis of L-threo-sphingosine, D-threo-sphingosine, L-threo-sphinganine and D-threo-sphinganine from commercially available L- or D-serine. The key steps are the simple preparation of trans-oxazoline and intermolecular olefin cross metathesis.
Subject(s)
Alkenes/chemistry , Oxazoles/chemistry , Protein Kinase C/antagonists & inhibitors , Protein Kinase Inhibitors , Sphingosine/analogs & derivatives , Molecular Structure , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Sphingosine/chemical synthesis , Sphingosine/chemistry , Sphingosine/pharmacology , Stereoisomerism , Structure-Activity RelationshipABSTRACT
Palladium(II)-catalyzed carboxylation of chiral olefins 6a-d has been examined under various conditions. In the weak basic condition (K2CO3), 7a-d were obtained in good yields. Alternatively, in the strong basic condition, pyrrolidinones 8a-d were obtained resulting in excellent yields and with high diastereoselectivity.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Pyrrolidinones/chemical synthesis , Pyrrolidinones/pharmacology , Alkenes/chemistry , Catalysis , Chromatography, Gel , Indicators and Reagents , Magnetic Resonance Spectroscopy , Palladium/chemistry , Solvents , StereoisomerismABSTRACT
2,3-Disubstituted indoles were synthesized by solid-phase reaction using the Fischer indole synthesis. A "traceless" silicon linker was employed with the silicon-carbon bonding being cleaved with TFA. An oxygen atom was placed into the middle of the spacer/linker so as to enhance solid-phase synthesis by better solvation.
Subject(s)
Indoles/chemistry , Indoles/chemical synthesis , Molecular StructureABSTRACT
In this study, a highly diastereoselective synthesis of anti-1,2-aminoalcohol was explored starting from L-amino acids as chiral sources. The higher yield and diastereoselectivity was shown when the aza-Claisen rearrangement was performed with allylic trichloroacetimidate 6a in the presence of palladium(II) catalyst.
Subject(s)
Amino Alcohols/chemical synthesis , Aza Compounds/chemistry , Palladium/chemistry , Catalysis , Hydroxylation , Indicators and Reagents , StereoisomerismABSTRACT
[reaction: see text] A concise, stereocontrolled synthesis of sphingofungin F was achieved. Key features involve diastereoselective oxazoline formation catalyzed by palladium(0), MgBr(2)-promoted gamma-alkoxy allylic stannane addition, and palladium(0)-catalyzed coupling of a vinyl iodide with an organozinc reagent.
Subject(s)
Amino Acids/chemistry , Amino Acids/chemical synthesis , Antifungal Agents/chemistry , Antifungal Agents/chemical synthesis , Fatty Acids, Unsaturated/chemistry , Fatty Acids, Unsaturated/chemical synthesis , Catalysis , Molecular Structure , Palladium/chemistry , StereoisomerismABSTRACT
Stereoselective syntheses of (+/-)-epibatidine analogues 2, which contain the 8-azabicyclo [3.2.1]octane ring system, were achieved by using palladium-catalyzed cross-coupling reaction from 4 and the analgesic activity was tested by Mouse writhing antinociceptive assay.
Subject(s)
Analgesics, Non-Narcotic/chemical synthesis , Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis , Nicotinic Agonists/chemical synthesis , Pyridines/chemical synthesis , Analgesics, Non-Narcotic/chemistry , Animals , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Catalysis , Indicators and Reagents , Magnetic Resonance Spectroscopy , Male , Mice , Mice, Inbred ICR , Nicotinic Agonists/chemistry , Pain Measurement/drug effects , Pyridines/chemistry , StereoisomerismABSTRACT
Syntheses of (+/-)-homoepibatidine analogues (2), which contain the 8-azabicyclo [3.2.1]octane ring system, were achieved by using palladium-catalyzed reductive-coupling reaction from 3 and the analgesic activity was tested by Mouse writhing antinociceptive assay.
