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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  1. Aaron Balog
    14 Balog
  2. Dongfang   Meng
    17 Meng
  3. Dai-Shi   Su
    12 Su