Stereoselective Construction of all-anti Polypropionate Modules: Synthesis of the C5−C10 Fragment of Streptovaricin U

Abstract

A concise non-aldol approach for the stereoselective construction of all-anti polypropionate fragments was developed. The iterative epoxide-based methodology consists of the syn-selective epoxidation of cis homoallylic alcohols using the VO(acac) 2 catalyzed conditions followed by epoxide cleavage with a propynyl aluminum reagent as key steps. The methodology was applied to the synthesis of the all-anti C6-C10 fragment of streptovaricin U.

Reiterative epoxide-based strategies for the synthesis of stereo-n-ads and application to polypropionate synthesis. A personal account

“…The close relationship between these two polyketides can be exploited by developing a divergent/convergent synthesis of these fragments from terminal epoxide 26 , itself derived from anti,anti ,cis epoxide 14 . The synthesis of the anti,anti stereotetrads was extensively studied for the stereoselective synthesis of the streptovaricin U fragment [29]. …”

“…The optically active stereotetrad 27 was prepared in 38% overall yield using two iterations of our anti,anti methodology [29]. Careful protecting group manipulation allowed the preparation of carbonate 28 with N,N’ -carbonyldiimidazole (CDI), favoring formation of the 1,2-carbonate over the 1,3-carbonate.…”

“…Its polypropionate fragment consists of nine stereocenters, with a carbomethoxy functionality at C10. The polypropionate fragment of streptovaricin U replaces the C10 carbomethoxy for a methyl group, and its synthesis was reported by us using our reiterative methodology [29]. The ansa chain of streptovaricin D has yet to see a synthesis.…”

“…Moreover, the different polypropionate permutations present can be obtained by selecting the correct combination of epoxide and nucleophile. This methodology was successfully applied to the synthesis of the all- anti C5–C10 polypropionate fragment of streptovaricin U and the C14–C25 bafilomycin A 1 polypropionate chain [29,30]. …”

Concise epoxide-based synthesis of the C14–C25 bafilomycin A1 polypropionate chain

“…31–33 This methodology has led to the successful linear synthesis of the all anti fragment of streptovaricin U and other polypropionate modules. 34 Aimed at extending our methodology to more varied polypropionate targets and to expand it from linear to convergent, herein we present an epoxide-based approach for the enantioselective synthesis of the C14–C25 polypropionate fragment of bafilomycin A 1 .…”