Mitomycins are an important class of antitumor antibiotics that have unique structural features. Our synthetic approach toward mitomycins includes the transannular cyclization of the eight-membered intermediate 1 at the later stage of the synthesis. The eight-membered lactam 4 which had been prepared by the reaction called "controlled crisscross annulation" was converted to p-quinone 12 by taking the advantage of the reactivity difference of the conformational isomers 9A and 9B. p-Quinone 12 was transformed into allylic alcohol 14 in 5 steps. Stereospecific introduction of aziridine ring onto the eight-membered ring was accomplished in high yield by the use of intramolecular cyclization reaction. Namely, iodocyclization of allylic carbamate 15 followed by methanolysis afforded aziridine 17 as a single diastereoisomer. The stereochemistry of aziridine 17 was determined by single X-ray crystallographic analysis. Treatment of ketone 18 with TBDMSOTf in the presence of Net_3 gave the cyclized product 19 in quantitive yield. It is noteworthy that this transannular cyclization reaction proceeded without elimination of the oxygen functional group at the bridgehead. Debenzylation of the compound 19 followed by oxidation smoothly provided p-quinone 20 in good yield. Deprotection of p-quinone 20 afforded decarbamoyloxymitomycin derivative 22, which has p-quinone, aziridine and hydroxy group in the molecule.
