Synthesis of chiral vinylsulfonium salts and their application in the synthesis of the mitomycin skeleton (Asymmetric epoxidation)

The mitomycins, antibacterial anticancer drugs have been extensively studied since their discovery in the 1950s. An efficient total synthesis may lead to a variety of new mitomycin analogs. However, total synthesis of mitomycin C challenges the synthetic chemist because of its structural complexity and instability.; The annulation reaction of dimethylvinylsulfonium iodide with the sodium salt of 2-formylindole followed by treatment with sodium azide forms a tricyclic azido alcohol which is a useful precursor in the racemic synthesis of the mitomycin skeleton. The synthesis of the enantiomerically pure mitomycin skeleton was tried using chiral vinylsulfonium salts reacted with 2-formylindole. Four chiral vinylsulfonium salts were prepared from camphor-derived compounds and they were used to synthesize a mitomycin precursor with an enantiomeric excess of up to 45%. After transferring the vinyl group to 2-formylindole in the annulation reaction, the chiral auxiliary sulfides were recovered in up to a 95% yield and can be recycled to regenerate the vinylsulfonium salt. Several approaches were tried to synthesize a vinylsulfonium salt with improved design in order to improve enantioselectivity.