| Abstract
| - An enantiocontrolled route to aziridinomitosenes had been developed from l-serine methyl esterhydrochloride. The tetracyclic target ring system was assembled by an internal azomethine ylide cycloadditionreaction based on silver ion-assisted intramolecular oxazole alkylation and cyanide-induced ylide generationvia a labile oxazoline intermediate (62 to 66). Other key steps include reductive detritylation of 26, methylationof the N-H aziridine 56, oxidation of the sensitive cyclohexenedione 68 to quinone 70, and carbamoylationusing Fmoc-NCO. Although the aziridinomitosene tetracycle is sensitive, a range of protecting groupmanipulations and redox chemistry can be performed if suitable precautions are taken. A study of DNAalkylation by the first C-6,C-7-unsubstituted aziridinomitosene 11a has been carried out, and evidence forDNA cross-link formation involving nucleophilic addition to the quinone subunit is described.
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