In a search for new epothilone analogs, it seems worthwhile to replace one of these methylene groups by a heteroatom such as oxygen or sulfur and this may be carried out at C9 or C10 (syntheses of 9-oxa [15] and 10-oxa [16] epothilones have been recently patented by the Schering group). We first selected 10-oxa EpoB and studied the effect of this modification on the conformational equilibrium of the macrocycle. It was found, at the AM1 level, [17] that 2 conformations of ...
