Abstract EN:

The goal of the present investigation was to assemble the 20-carbon unit of the taxoid diterpene skeleton in a step efficient and stereocontrolled way. We have developed an attractive approach that relies on the aldol reaction. The requisite taxoid diterpene carbon skeleton was prepared from two achiral aldol partners derived from methylcyclopentenone and benzoic acid. The central role played by the enolate geometry for the simple diastereoselection during the formation of the C9-C10 bond, has led to the accumulation of an enormous wealth of control elements. To avoid the problems associated with 8-membered B-ring formation, our strategy was based on a fragmentation rather than a ring closure operation. We investigated ways for the introduction of the C-11 functionality, necessary for the C11-C12 ring closure. Methods for accomplishing this synthetic transformation at carbon atoms adjacent to olefins, ketones or alcohols especially in highly functionalized eight-membered ring templates, heavily substituted in periphery, face difficulties inherent to the ring system. We explored conditions for connecting the C-11/C-12 carbons to complete the synthesis of the ABC ring system and finally achieved a convenient, stereocontrolled synthesis of the taxoid ABC subunit embodying the whole carbon framework and most of the required oxygen functionalities. The efficiency of the synthetic sequence allows us to continue on the synthesis of target molecules, to include a route which would be amenable to a series of taxoid representatives with minor structural modifications. To summarize, the aldol-annelation-fragmentation approach represents a working method for the taxoid construction.