(A) formal total synthesis of crinipellin B

Abstract

There is only one group of natural products having a tetraquinane framework, crinipellins. An investigation of several strains of basidomycete Crinipellis stipitaria has lead to the isolation of five new diterpenoids, containing a unique tetraquinane carbon framework, a combination of linear and angular tetraquinane moieties. Though there have been a lot of synthetic approaches to crinipellins, total synthesis was reported only once by Piers. A new efficient way to generate TMM diyl was developed with allene and N-aziridinylimines which was successfully utilized in [2+3] cycloaddition reaction with olefins. The novel one pot sequential transformation of thermally labile pyrazoles obtained through [2+3] cycloaddition reaction of diazoalkanes with allenes produced TMM diyls and the generated diyls were trapped by olefin to form polyquinane. Tetraquinane structure of Crinipellin B was assembled stereoselectively through thermolysis of allenyl aziridinylimine and further functional group modification provided Piers’ intermediate in his total synthesis of Crinipellin B. This formal total synthesis of Crinipellin B was accomplished in 14 steps sequence. Furthermore, we found out the separation condition of the enantiomers of the starting cyclopentanone that shows the possibility of asymmetric total synthesis of Crinipellin B.