Diastereo- and enantioselective total synthesis of stigmatellin A

Stigmatellin A (1) isolated from the myxobacterium Stigmatella aurantiaca is a powerful inhibitor of electron transport in mitochondria and chloroplasts. The first highly diastereo- and enantioselective total synthesis of this important natural product is described. Key steps in the synthesis are the alkylation of the SAMP-hydrazone (S)-13, a titanium mediated syn-diastereoselective aldol reaction, the anti-diastereoselective triacetoxyborohydride reduction of the aldol adduct (R,R,S)-16, formation of the chromone system via Baker Venkataraman rearrangement and exclusive (E) C=C double bond formation via Horner-Wadsworth-Emmons reaction.