Total Synthesis of Cyanolide A in the Absence of Protecting Groups, Chiral Auxiliaries, or Premetalated Carbon Nucleophiles

摘要

Cyanolide A is a glycosidic 16-membered macrodiolide of C2 symmetry isolated from the Papua New Guinea cyano-bacterium Lyungbya bouillonii and is closely related in structure to the clavosolide family of natural products (Figure l). Cyanolide A exhibits potent molluscicidal activ- of infected water snails is more desirable. The molluscicide niclosamide (bayluscide) was developed for this purpose and is utilized broadly. However, it exhibits poor water solubility, is rather nonselective, adversely affects native fish, and is relatively expensive. Hence, an authentic need for alternative molluscicidal agents persists, thus fueling efforts toward the synthesis of naturally occurring molluscicides. Toward this end, cyanolide A has garnered significant attention from organic chemists, with several total and formal syntheses published since its isolation in 2010 (Figure l). Herein, we report a total synthesis of cyanolide A in the absence of protecting groups, chiral auxiliaries, or premetalated C-nucleophiles in fewer than half the steps of any previous approach.