Synthesis of Mitomycins

Abstract

This chapter describes mitomycin syntheses published in the period 1984–1988 plus 1989 literature available by August 1. Mitomycin synthesis was intensively investigated in this period. It is characterized by a considerable variety of strategies and novel chemistry. The most significant accomplishment was an efficient new total synthesis of mitomycin С by way of isomitomycin A. Other achievements include syntheses of decarbamoyl 7-methoxymitosane by electrophile-initiated biscyclization and by a copper-catalyzed double cyclization of an azidoquinone. New methods for 9,9a-dihydromitosenes were based on photocyclization of a diene-bearing azidoquinone and on intramolecular Reformatsky or Wittig reactions. A stereoselective synthesis of a 1,2-aziridinomito- sene involved photochemical oxidation-reduction followed by palladium-catalyzed cyclization. Mitosenes were prepared by a variety of strategies including triazole photolysis, “criss-cross” annulation of a 2-[2-(l,3-dioxocyclopentanyl)]aniline, Madelung synthesis, and Dieckmann cyclization of a substituted pyrrolazene. Other approaches were based on thermal isomerization of a 1-(1-pyrrolidinyl)-2-vinylbenzene, palladium-catalyzed cyclization of a 6-allyl-5-allylamino-1,4- benzoquinone, and intramolecular cycloaddition of a nitrile oxide to a vinyl group. A 1,2- cyclopropano derivative was formed by 1,3-dipolar addition of a diazo group to an alkene, followed by elimination of nitrogen.