Total synthesis and evaluation of cytostatin, its C10-C11 diastereomers, and additional key analogues: impact on PP2A inhibition.

ABSTRACT: The total synthesis of cytostatin, an antitumor agent belonging to the fostriecin family of natural products, is described in full detail. The convergent approach relied on a key epoxide-opening reaction to join the two stereotriad units and a single-step late-stage stereoselective installation of the sensitive (Z,Z,E)-triene through a beta-chelation-controlled nucleophilic addition. The synthetic route provided rapid access to the C4-C6 stereoisomers of the cytostatin lactone, which were prepared and used to define the C4-C6 relative stereochemistry of the natural product. In addition to the natural product, each of the C10-C11 diastereomers of cytostatin was divergently prepared (11 steps from key convergence step) by this route and used to unequivocally confirm the relative and absolute

SUBMITTER: Lawhorn BG 

PROVIDER: S-EPMC2566737 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature