Analogs of dictyostatin, intermediates therefor and methods of synthesis thereof

Abstract

Dictyostatin and its analogs show great promise as new anticancer agents. The present invention provides dictyostatin analogs, synthetic intermediates for the synthesis of dictyostatin analogs, and synthetic methods for the synthesis of such analogs and intermediates. Dictyostatin analogs can have the following structure or its enantiomer wherein Ris H, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, or a halogen atom; Ris H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRRR, CHOR, or COR; R, Rand Rare independently an alkyl group or an aryl group; Ris an alkyl group, an aryl group, an alkoxylalkyl group, —RSiRRRor a benzyl group, wherein Ris an alkylene group; Ris an alkyl group, an allyl group, a benzyl group, an aryl group, an alkoxy group, or —NRR, wherein Rand Rare independently H, an alkyl group or an aryl group; Ris (CH)where n is and integer in the range of 0 to 5, —CHCH(CH)—, —CH═CH—, —CH═C(CH)—, or —C≡C—; Ris wherein Ris H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRRR, CHOR, or COR; Ris H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRRR, CHOR, or COR, or Rand Rtogether form a portion of six-membered acetal ring incorporating CRR; Rand Rare independently H, an alkyl group, an aryl group or an alkoxyaryl group; and Ris H or OR, wherein Ris H, a protecting group, an alkyl group, an aryl group, a benzyl group, a trityl group, —SiRRR, CHOR, or COR; provided that the compound is not dictyostatin 1.