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 subsequent asymmetric hydrogenation to generate the corresponding all-syn oxazine 4 with excellent diastereoselectivity. Conversion of 4 into beta-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.
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, USA.
Rajendra P
RP
Jain
Robert M
RM
Williams
D000599:Amino Acids, Diamino / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D003516:Cycloparaffins / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D015394:Molecular Structure; D010078:Oxazines / Q000737:chemistry; D010455:Peptides; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry*
C472457:4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-one; D000599:Amino Acids, Diamino; D000900:Anti-Bacterial Agents; D003516:Cycloparaffins; D007783:Lactones; D010078:Oxazines; D010455:Peptides; C100200:negamycin