189453-40-5Relevant academic research and scientific papers
Rapid access to epothilone analogs via semisynthetic degradation and reconstruction of epothilone D
Dong, Steven D.,Sundermann, Kurt,Smith, Karen M. J.,Petryka, Joseph,Liu, Fenghua,Myles, David C.
, p. 1945 - 1947 (2004)
A facile and efficient route to epothilone analogs has been developed from the natural product epothilone D (1). Degradation of 1 via an oxidative cleavage sequence provides acid intermediate 4 rapidly in six steps. From 4, a variety of epothilone analogs have been prepared utilizing ring-closing metathesis to reconstruct the trisubstituted-12,13-double bond. Using this approach, we report a number of epothilone analogs with varying C-15 aromatic side chains and C-14 allylic substitutions and their biological activities.
Catalytic antibody route to the naturally occurring epothilones: Total synthesis of epothilones A-F
Sinha, Subhash C.
, p. 1691 - 1702 (2007/10/03)
Naturally occurring epothilones have been synthesized starting from enantiomerically pure aldol compounds 9-11, which were obtained by antibody catalysis. Aldolase antibody 38C2 catalyzed the resolution of (±)-9 by enantioselective retro-aldol reaction to afford 9 in 90% ee at 50% conversion. Compounds 10 and 11 were obtained in more than 99% ee at 50% conversion by resolution of their racemic mixtures using newly developed aldolase antibodies 84G3, 85H6 or 93F3. Compounds 9, 10 and 11 were resolved in multigram quantities and then converted to the epothilones by metathesis processes, which were catalyzed by Grubbs' catalysts.
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.
