The first total synthesis of roquefortine C is achieved by implementation of a novel elimination strategy to construct the thermodynamically unstable E-dehydrohistidine moiety. Molecular modeling studies are presented which explain the instability of the roquefortine C structure compared to that of isoroquefortine C.

Alkaloids U 0600The Total Synthesis of Roquefortine C and a Rationale for the Thermodynamic Stability of Isoroquefortine C over Roquefortine C. -Molecular modeling studies explain the instability of the (E)-configurated title compound (Ia) compared to that of the unnatural isoroquefortine C (Ib). -(SHANGGUAN, N.; HEHRE, W. J.; OHLINGER, W. S.; BEAVERS, M. P.; JOULLIE*, M. M.; J.