ANALOGS OF DICTYOSTATIN, INTERMEDIATES THEREFOR AND METHODS OF SYNTHESIS THEREOF

摘要

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 (I) wherein R<1> is H, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, or a halogen atom; R<2> is H, a protecting group, an alkyl group, a benzyl group, a trityl group, -SiRRR, CH2OR, or COR; R, R and R are independently an alkyl group or an aryl group; R is an alkyl group, an aryl group, an alkoxylalkyl group, -R SiRRR or a benzyl group, wherein R is an alkylene group; R is an alkyl group, an allyl group, a benzyl group, an aryl group, an alkoxy group, or -NRR, wherein R and R are independently H, an alkyl group or an aryl group; R<3> is (CH2)n where n is and integer in the range of 0 to 5, -CH2CH(CH3)-, -CH=CH-, -CH=C(CH3)-, or -C=C-; R<4> is (II) wherein R<23a> is H, a protecting group, an alkyl group, a benzyl group, a trityl group, -SiRRR, CH2OR, or COR, R<23b> is H, a protecting group, an alkyl group, a benzyl group, a trityl group, -SiRRR, CH2OR, or COR, or R<23a> and R<23b> together form a portion of six-membered acetal ring incorporating CRR; R and R are independently H, an alkyl group, an aryl group or an alkoxyaryl group; and R<5> is H or OR<2b>, wherein R<2b >is H, a protecting group, an alkyl group, an aryl group, a benzyl group, a trityl group, -SiRRR, CH2OR, or COR; provided that the compound is not dictyostatin 1.