US 2008/0188651 A1 · Analogs of dictyostatin, intermediates therefor and methods of systhesis 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 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.

Claims4

Dependent claims

A compound having the following formula, or its enantiomer

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, —RSiRaRbRc 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), where n is and integer in the range of 0 to 5, —CH2CH(CH3)—, —CH═CH—, —CH═C(CH3)—, or —C≡C—;
R11a and R11b are independently H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, CORe, or R11a and R11b together form a portion of six-membered acetal ring containing CRtRu;
Rt and Ru are independently H, an alkyl group, an aryl group or an alkoxyaryl group;
R12 is a halogen atom, CH2OR2c, CHO, CO2R10, CH═CHCH2OR2c, CH═CHCHO or CH═CHCO2R10, wherein R2c is H, a protecting group, an alkyl group, an aryl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe, and R10 is H or alkyl;
and
R14a and R14b are independently H, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, CORe, or R14a and R14b together form a six-membered ring containing CRvRw, wherein Rv and Rw are independently H, an alkyl group, an aryl group or an alkoxyaryl group.

7 more elements

Dependencies are inferred from the claim text.

Analogs of dictyostatin, intermediates therefor and methods of systhesis thereof

Life of this patent

Analogs of dictyostatin, intermediates therefor and methods of systhesis thereof

Life of this patent

Abstract

Claims4