APPROACHES TO A SYNTHESIS OF GALBONOLIDE-B

An approach to the C(7)-C(15) fragment of galbonolide B 2 has been com pleted in which the diene fragment 51 was assembled from (R)-3-tert-bu tyldimethylsilyloxypentan-2-one 29 by conversion into the unsaturated ester 30, acylation of the sulfone 47 using this ester, reductive desu lfurisation, methylenation using a Wittig reaction and deprotection. F ollowing model studies, the aldehyde 62, prepared by oxidation of the alcohol 51, was converted into a mixture of the epimeric alcohols 63 a nd these were converted into the di(methylene)tridecadienoic acid 65 u sing a phosphine catalysed Ireland-Claisen rearrangement. Sharpless ep oxidations of the alcohol 67 using either L-(+)- Or D-(-)-diethyl tart rate were highly stereoselective and gave the epoxides 68 and 69 which were clearly distinguishable. Model studies using the heptadiene mono epoxide 70 led to a synthesis of the monoprotected dihydroxy aldehyde 76 so establishing a protocol for the introduction into the vicinal di ol of the galbonolides. Finally, aldol addition of tert-butyl acetate to the aldehyde 78 followed by selective protection, deprotection and cyclisation completed a synthesis of the macrolide 85.