TOTAL SYNTHESIS OF GRAHAMIMYCIN-A1

(3R)- and (3S)-3-Hydroxybutanoates were respectively converted into (2E,5R)- and (2E,5S)-5-t-butyldi-methylsiloxy-2-hexenoic acids, corresponding to the 0-1-C-6 fragment of grahamimycin Al (1). The 0-7 C-14 fragment [(4S,5S,7R)- or (4R,5R.7R)-7-hydroxy-4,5-isopropylidenedioxyoctanoate] was synthesized from 4,6-dideoxy-alpha-D-xylo-hexopyranoside. Condensation of the both fragments. followed by deprotection at the terminal hydroxyl- and carboxyl-functions afforded the seco acids of the precursors of 1. While the reaction of the seco acids having 13S-configuration with diethyl azodicarboxylate and triphenylphosphine afforded the corresponding lactones in low yields, macrolactonization of the seco acid having 13R-configuration by Yamaguchi procedure gave the desired lactone in 56% yield. Deprotection of vic-diol moiety of the lactone indicated the completion of relay synthesis of 1.