An isocoumarin route to resorcylic acid lactones (RALs): asymmetric total synthesis of neocosmosin A, fusariumin and penicipyran D

Abstract

We disclose a concise asymmetric synthesis of a naturally occurring RAL, neocosmosin A, from an appropriately substituted isocoumarin framework. The isocoumarin was constructed through Ag(I)-mediated 6-endo-dig cyclization of appropriately substituted 2-alkynylated benzoates. The same isocoumarin compound was synthetically manipulated to naturally occurring fusariumin in a diverted way. The total synthesis of another naturally occurring isocoumarin, penicipyran D, was also accomplished for the first time through Ag(I)-catalysed 6-endo-dig cyclization of penta-substituted 2-alkynylated benzoates. An improved synthesis of neocosmosin A was also established through a late-stage RCM reaction from an isocoumarin-derived advanced intermediate.