Analogs of dictyostatin, intermediates therefor and methods of synthesis thereof

US7321046B2 · kind B2 · utility

Assignee

• UNIVERSITY OF PITTSBURGH · US

Inventors

• Dennis P. Curran · Pittsburgh, US
• Youseung Shin · North Palm Beach, US
• Jean-Hugues Fournier · Montréal, CA
• John Mancuso · Vaudreuil-Dorion, CA
• Billy W. Day · Pittsburgh, US
• Arndt Bruckner · Neheim, DE
• Yoshikazu Fukui · Osaka, JP

Key dates

• Filing date: May 27, 2005
• Grant date: Jan 22, 2008
• Expiry date: May 27, 2025

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02P20/55
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

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 enantiomerwherein 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 iswherein 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 tri…