Total syntheses of epothilones A and B Journal Article
| Authors: | Meng, D.; Bertinato, P.; Balog, A.; Su, D. S.; Kamenecka, T.; Sorensen, E. J.; Danishefsky, S. J. |
| Article Title: | Total syntheses of epothilones A and B |
| Abstract: | 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 nonenolizable 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. |
| Keywords: | organic-synthesis; secondary alcohols; ring-closing metathesis; olefin metathesis; cross-coupling reactions; rifamycin-s; dess-martin; periodinane; cyclocondensation reactions; unsaturated sugars; ethyl diazoacetate |
| Journal Title: | Journal of the American Chemical Society |
| Volume: | 119 |
| Issue: | 42 |
| ISSN: | 0002-7863 |
| Publisher: | American Chemical Society |
| Date Published: | 1997-10-22 |
| Start Page: | 10073 |
| End Page: | 10092 |
| Language: | English |
| ACCESSION: | WOS:A1997YD32000016 |
| DOI: | 10.1021/ja971946k |
| PROVIDER: | wos |
| Notes: | Review -- Source: Wos |
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