Stereoselective Synthesis of the C1-C16 Fragment of the Purported Structure of Formosalide B.

Abstract

The first stereoselective synthesis of the C1–C16 fragment possessing stereo-enriched fully substituted tetrahydropyran (THP) along with tetrahydrofuran (THF) rings of the proposed structure of formosalide B is described in 12 longest linear steps with 22% overall yield, starting from two cheap and commercially available 1,5-pentanediol and l-glutamic acid, following a convergent approach. The key steps involve in this synthesis are Horner–Wadsworth–Emmons reaction, Sharpless asymmetric dihydroxylation, and acid-mediated ketalization to assemble the substituted THP ring, one-pot Sharpless dihydroxylation–SN2-type cyclization, and Wittig homologation to construct the THF derivative.