Total synthesis of the crinipellins

Abstract

Crinipellins are the only natural products with AB tetraquinane framework. The highly congested structure with eight stereogenic centers and highly reactive functional groups make it a great challenge for total synthesis. The total synthesis of crinipellin A and B was achieved using tandem cycloaddition reaction strategies via a trimethylenemethane (TMM) diyl-mediated [2+3] cycloaddition reaction. A formal total synthesis of crinipellin B preceded the asymmetric total synthesis of crinipellin A through the tandem [2+3] cycloaddition reaction of a diazoallenyl substrate containing a cyclopentane ring. The substrate for the cycloaddition reaction was prepared enantioselectively and subsequent selective functional group manipulation completed the first asymmetric total synthesis of crinipellin A.