197233-41-3Relevant academic research and scientific papers
Total Synthesis of Epothilones A and B
Dongfang, Meng,Bertinato, Peter,Balog, Aaron,Su, Dai-Shi,Kamenecka, Ted,et al.
, p. 10073 - 10092 (2007/10/03)
Convergent, stereocontrolled total syntheses of the microtubule-stabilizing macrolides epothilones A (2) and B (3) have been achieved. Four distinct ring-forming strategies were pursued (see Scheme 1). Of these four, three were reduced to practice. In one approach, the action of a base on a substance possessing an acetate ester and a nonenolazable aldehyde brought about a remarkably effective macroaldolization see (89 -> 90 + 91; 99 -> 100 + 101), simultaneously creating the C2-C3 bond and the hydroxyl-bearing stereocenter at C-3. Alternatively, the 16-membered macrolide of the epothilones could be fashioned through a C12-C13 ring-closing olefin metathesis (e.g. see 111 -> 90 + 117; 122 -> 105 + 123) and through macrolactonization of the appropriate hydroxy acid (e.g. see 88 -> 93). The application of a stereospecific B-alkyl Suzuki coupling strategy permitted the establishment of a cis-C12-C13 olefin, thus setting the stage for an eventual site- and diastereoselective epoxidation reaction (see 96 -> 2; 106 -> 3). The development of a novel cyclopropane solvolysis strategy for incorporating the geminal methyl groups of the epothilones (see 39 -> 40 -> 41), and the use of Lewis acid catalyzed diene-aldehyde cyclocondensation (LACDAC) (see 35 + 36 -> 37) and asymmetric allylation (see 10 -> 76) methodology are also noteworthy.
