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Stereocontrolled Total Synthesis of Nonenolide
Purushotham Reddy Sudina1, Damoder Reddy Motati1, Aravind Seema2
1Division of Natural Product Chemistry , CSIR-Indian Institute of Chemical Technology , Hyderabad - 500007 , India.
Abstract:
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.
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