Total synthesis of the antimitotic bicyclic peptide celogentin C.

ABSTRACT: An account of the total synthesis of celogentin C is presented. A right-to-left synthetic approach to this bicyclic octapeptide was unsuccessful due to an inability to elaborate derivatives of the right-hand ring. In the course of these efforts, it was discovered that the mild Braslau modification of the McFadyen-Stevens reaction offers a useful method of reducing recalcitrant esters to aldehydes. A left-to-right synthetic strategy was then examined. The unusual Leu-Trp side-chain cross-link present in the left-hand macrocycle was fashioned via a three-step sequence comprised of an intermolecular Knoevenagel condensation, a radical conjugate addition, and a SmI(2)-mediated nitro reduction. A subsequent macrolactamization provided the desired ring system. The high yield and concise nature o

SUBMITTER: Ma B 

PROVIDER: S-EPMC2810426 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature