Analogs of dictyostatin, intermediates therefor and methods of systhesis 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 wherein R1 is H, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, or a halogen atom; R2 is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; Ra, Rb and Rc are independently an alkyl group or an aryl group; Rd is an alkyl group, an aryl group, an alkoxylalkyl group, —RiSiRaRbRc or a benzyl group, wherein Ri is an alkylene group; Re is an alkyl group, an allyl group, a benzyl group, an aryl group, an alkoxy group, or —NRgRh, wherein Rg and Rh are independently H, an alkyl group or an aryl group; R3 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—; R4 is wherein R23a is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe, R23b is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe, or R23a and R23b together form a portion of six-membered acetal ring incorporating CRtRu; Rt and Ru are independently H, an alkyl group, an aryl group or an alkoxyaryl group; and R5 is H or OR2b, wherein R2b is H, a protecting group, an alkyl group, an aryl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; provided that the compound is not dictyostatin 1.
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