| Research Abstract |
The segments, C_1-C_<13> and C_<15>-C_<21>, containing the thirteen stereogenic centers required for the frame of (+)-discodermolide, were synthesized in good to excellent enantio-and diastereoselectivities from a common racemic aldehyde, derived from 2-methyl-1,3-propanediol. The enantioselective aldol reactions of the racemic aldehyde with a silylketene acetal, derived from ethyl 2-bromopropionate, in the presence of chiral oxazaborolidinones, prepared in situ -with N-p-toluenesulfonyl-(R)-and -(S)-valine and BH_3-THF, proceeded under kinetic control to give the stereotriads with a high degree of enantioselectivity. Enantioselective(chiral borane) and diastereoselective(BF_3-OEt_2 and TiCl_4) aldol reactions with the silylketene acetal, coupled with diastereoselective radical debrominations(Bu_3SnH,Et_3B, with or without MgBr_2) were used iteratively. This aldol reaction strategy for the construction of the polypropionate frame to dramatically shortened the steps needed for the construction of the final segments.
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