Venturicidin A, B and Irumamycin, isolated from some streptomyces, are 20-membered macrolide antibiotics and inhibit effectively the growth of the phytopathogenic fungi. We have already determined the absolute structure of C_<16>-C_<22> part of irumamycin by stereoselective synthesis of the degradation product. We now report the first total synthesis of the aglycone of venturicidin A and B. Compound 14 involving four chiral centers has been synthesized in the process of determining the stereostructure of irumamycin based on the lipase-catalyzed kinetic hydrolysis and stereoselective ketone reduction and was converted to the upper half 22 in 20 steps. The bottom half 43 was prepared by regioselective dehydration of 41, which was derived from (7S)-alcohol 39. Both fragments were condensed by Yamaguchi's method to give the ester which was deprotected to give the alcohol 44. Oxidation of 44 followed by cyclization (Nicolaou's procedure) provided the 20-membered enone 45, which was reduced with NaBH_4-CeCl_3 to a separable 1:1 mixture of 46a,b. One of the isomers 46a was converted to 50a whose NMR spectrum was found to be identical with the reported spectrum of venturicidin A and B aglycone.
