A concise enantioselective total synthesis of (+)-epi-muricatacin, using asymmetric hydrogenation/intramolecular iodoetherification as key steps

A concise enantioselective total synthesis of (+)-epi-muricatacin, a potent cytotoxic agent, is described. A key feature of this protocol is a catalytic asymmetric hydrogenation and a chiral auxiliary mediated intramolecular iodoetherification to ensure a high degree of distereo- and enantiocontrol.

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tert-Butyl((S)-2-((2S,5S,6S)-5,6-diphenyl-1,4-dioxan-2-yl)-2 iodoethoxy)dimethylsilaneC24H33IO3Si[α]D25=-39.0 (c 1, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: ((S)-2-(2S,5S,6S))

(2S,3S,5S)-5-((R)-Oxiran-2-yl)-2,3-diphenyl-1,4-dioxaneC18H18O3[α]D25=+39.5 (c 1, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: ([2S,3S,5S]-5R-oxirane)

(R)-1-((2S,5S,6S)-5-6-Diphenyl-1,4-dioxan-2-yl)tridecan-1-olC29H42O3[α]D25=-20.0 (c 1, CHCl3)Source of chirality: asymmetric hydrogenationAbsolute configuration: (R)-1-(2S,5S,6S)