Total Syntheses of Epothilones A and B via a Macrolactonization-Based Strategy
Citations Over TimeTop 10% of 1997 papers
Abstract
The total syntheses of epothilones A (1) and B (2) and several analogues thereof are described. The reported strategy relies on a macrolactonization approach and features selective epoxidation of the macrocycle double bond in precursors 3 and 4 (Scheme 1), respectively, as well as high convergency and flexibility. Building blocks 9−12 and 15 were constructed by asymmetric processes and coupled via Wittig, aldol, and macrolactonization reactions to afford the basic skeleton of epothilones and that of several of their analogues by a relatively short route. The utilization of intermediate 14, obtained via a stereoselective Wittig reaction and its Enders coupling to SAMP hydrazone 13 (Scheme 8), in combination with a stereoselective aldol reaction with the modified substrate 69 (Scheme 10) improved the stereoselectivity and efficiency of the total synthesis of these new and highly potent microtubule binding antitumor agents.
Related Papers
- → Epothilones: Promising Natural Products with Taxol‐Like Activity(1997)35 cited
- → Recent Progress in the Synthesis of Epothilones(2004)11 cited
- → Synthetic Methodologies for the Preparation of Epothilones and Analogs(2006)8 cited
- → The Aldol Reaction in Natural Product Synthesis: The Epothilone Story(2004)14 cited
- → Epothilones(2007)