SB-311009

The proposed structures of jenamidines A, B, and C (1-3) were revised to jenamidines A1/A2, B1/B2, and C (8-10). Jenamidines A1/A2 (8) were synthesized from activated proline derivative 43 by conversion to 26 in two steps and 50% overall yield. Acylation of 26 with acid chloride 38d gave 39d, which was deprotected with TFA and then mild base to give 8 in 45% yield from 26. (-)-trans-2,5-Dimethylproline ethyl ester (49) was prepared by the enantioselective Michael reaction of ethyl 2-nitropropionate (51) and methyl vinyl ketone (50) using modified dihydroquinine 60 as the catalyst. Further elaboration converted 49 to natural (+)-NP25302 (12). A Wittig reaction of proline NCA (76) with ylide 79 gave 72 as a 9/1 E/Z mixture in 27% yield, completing a one-step formal synthesis of SB-311009 analogues.

A series of novel inhibitors of lipoprotein associated phospholipase A2 were isolated from the culture broths of Pseudomonas fluorescens strain DSM11579. The inhibitors fall into two structurally isomeric classes each of which comprise compounds incorporating glycosylated hydrocarbon chains. The structure elucidation for the major member of each structural class is reported. The crystal structure of a non-glycosylated analogue of the 5,5-series, produced through biotransformation, is also reported.