ORGN 386

The Mitomycin family of natural products displays cytoxic properties.  Of these, Mitomycin C is used clinically as a chemotherapeutic agent against a variety of solid tumors.  Aziridinomitosene B (1) is a reductive product of Mitomycin B that upon activation exhibits the same activity as the mitomycins, namely DNA crosslinking.  Our synthetic strategy relies upon a single key transformation to generate the tetracyclic core from 2.  This occurs via ring opening of the substituted oxazole 2 to generate an azomethine ylide which undergoes a [3+2] cycloaddition with the tethered dipolarophile.  We report herein the synthesis of the azomethine ylide precursor (2), which possesses the entire carbon skeleton of the aziridinomitosenes.