Total Synthesis of Korormicin

Abstract

Recently, we have assigned the (5S,3′R,9′S,10′R) stereochemistry to planar korormicin (1) on the basis of the specific rotations of the four possible diastereoisomers [i.e., (5S,3′R,9′S,10′R), (5S,3′S,9′S,10′R), (5S,3′S,9′R,10′S), and (5S,3′R,9′R,10′S) isomers], which were prepared by a total synthesis. In this article, we describe the synthetic aspects in detail. The intermediates in the synthesis are enamino lactone (5S)-4 and both enantiomers of acid 5 and of boronate ester 7. Lactone (5S)-4 and boronate 7 with (9′S,10′R) and (9′R,10′S) chiralities were prepared through asymmetric dihydroxylation of olefins 11 and 30, respectively, with AD-mix-α or -β. Compounds (3′R)- and (3′S)-5 were prepared by kinetic resolution of rac-19 with asymmetric epoxidation. Condensation of (5S)-4 and (3′R)- or (3′S)-5 with DCC in the presence of DMAP and PPTS furnished the advanced intermediate 6 with (5S,3′R) and (5S,3′S) chiralities in good yields. Addition of PPTS was important to prevent formation of acyl urea 24. A nickel-catalyzed coupling reaction between 6 and 8 [prepared in situ from (9′S,10′R)- or (9′R,10′S)-7 and MeLi] produced 9, which upon deprotection with Bu4NF furnished the four diastereoisomers of korormicin (1).