Abstract
An efficient synthesis of epothilone D analogs of type 1 has been developed, which is based on a highly diastereoselective Evans aldol reaction as one of the key steps. A profound difference in the relative stabilities of TBS-protecting groups on C7-O and C15-O was observed between secondary and primary amide groups at C5-N4. Although modeling studies had suggested analogs of type 1 to assume a conformation similar to the NMR-derived conformation of tubulin-bound epothilone A, compounds 1a-d were found to be significantly less active than the parent compound epothilone D.
Key words
epothilones - total synthesis - aldol reaction - microtubule inhibitors - natural products
References
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15 The results of the biological evaluations will be published separately.
