6-Demethyl-6-halo- and 6-Demethyl-6-thiomitomycins: Synthesis of Novel Mitomycin Derivatives Involving a Tandem Michael Addition/Retro-Mannich Reaction Sequence

Synthesis of novel 6-demethyl-6-halomitomycins (3, 4, 6, and 7) and 6-demethyl;6-thiomitomycins (5 and 8) is described from key intermediates, namely, 6-demethyl-7,7-(ethylenedioxy)-6,6-dihalo-6,7-dihydromitosanes (18 and 19) and 6-demethyl-7,7-(ethylenedioxy)-6,7-dihydro-6-thiomitosane (20), respectively. Compounds 18-20 were prepared through a tandem Michael addition and a retro-Mannich reaction sequence (N-halosuccinimide or cationic arylsulfenyl species in the presence of Et 2 NH) on 10