Stereocontrolled Total Synthesis of Nonenolide.

Nonenolide (1) was first isolated from the entomopathogenic fungus Cordyceps militaries BCC2816 and exhibited good antimalarial activity against Plasmodium falciparum K1. Structurally, it features a decanolide with a trans-double bond attached to two chiral hydroxy groups, making the total synthesis of the exclusive isomer of 1 more difficult. Herein, we report the successful synthesis of 1 by employing a MacMillan α-hydroxylation to generate three chiral centers in both the key fragments, starting from 1,6-hexanediol and 1,4-butanediol, followed by Steglich esterification of compounds 2 and 3. The exclusive E-isomer was obtained via a ring-closing metathesis of the mono-PMB-protected diene 19. Deprotection provided the required natural product 1.