Isocoumarin route to the construction of resorcylic acid lactones (RALs): Asymmetric total synthesis of naturally occurring RAL neocosmosin A and isocoumarin containing fusariumin, penicipyran D

Abstract

We disclose a concise asymmetric synthesis of naturally occurring RAL, neocosmocin A, from a properly substituted isocoumarin framework. The isocoumarin was constructed through Ag(I) mediated 6-endo-dig cyclization of properly substituted 2-alkynylated benzoates. The same isocoumarin compound was synthetically manipulated to naturally occurring fusariumin in a diverted way. 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 late-stage RCM reaction from an isocoumarin-derived advanced intermediate.