Asymmetric Synthesis of (+)-Negamycin

An asymmetric synthesis of the antibiotic (+)-negamycin (1) has been achieved, starting from commercially available (5R,6S)-4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-one (2). The synthesis involved the stabilized Wittig olefination of the lactone carbonyl group of 2 and s...

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Bibliographic Details
Published in:Journal of organic chemistry 2002-09, Vol.67 (18), p.6361-6365
Main Authors: Jain, Rajendra P, Williams, Robert M
Format: Article
Language:English
Subjects:
Aliphatic compounds
Amino Acids, Diamino - analysis
Amino Acids, Diamino - chemical synthesis
Amino Acids, Diamino - chemistry
Anti-Bacterial Agents - analysis
Anti-Bacterial Agents - chemical synthesis
Anti-Bacterial Agents - chemistry
Catalysis
Chemistry
Cycloparaffins - chemistry
Exact sciences and technology
Lactones - chemistry
Molecular Structure
Organic chemistry
Oxazines - chemistry
Peptides
Preparations and properties
Stereoisomerism
Streptomyces - chemistry
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Summary:An asymmetric synthesis of the antibiotic (+)-negamycin (1) has been achieved, starting from commercially available (5R,6S)-4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-one (2). The synthesis involved the stabilized Wittig olefination of the lactone carbonyl group of 2 and subsequent asymmetric hydrogenation to generate the corresponding all-syn oxazine 4 with excellent diastereoselectivity. Conversion of 4 into β-alkoxy imine 7 and subsequent CeCl3-promoted chelation-controlled allylation of 7 generated the corresponding homoallylamine 8 with good diatereoselectivity, which was readily converted into (+)-negamycin (1) in 25% overall yield over 11 steps.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo025636i