The mitomycin antibiotics. Synthetic studies. XX. N-Substituted carbamoyl and acyl esters of a related 3-(hydroxymethyl)indole-4,7-dione

Mitomycins syntheses: a recent update

“…Unfortunately, these compounds did not show any anti-tumour activity [136]. Starting with the tricyclic ketone 181 [137–138] a low yielding bromination reaction was undertaken followed by an acetate displacement of the resulting α-bromoketone to give 182 (Scheme 50). The amine was introduced by formation of an oxime followed by catalytic hydrogenation in the presence of acetic anhydride to give the cis acetamido-acetate 183 .…”

Mitomycin antibiotics. Synthesis and activity of 1,2-disubstituted mitosenes

“…Elaboration of the quinone ring and hydroxymethyl groups, affording 14, was accomplished by procedures developed for 1-substituted mitosenes.4 This involved in sequence (7 -* 8 -*• 9 -*• 13 -* 14) Vilsmeier-Haack formylation, nitration, iron-in-acetic acid reduction followed by potassium nitrosodisulfonate oxidation, and sodium borohydride reduction followed by ferric chloride oxidation. As previously encountered with 1-acetamido analogues, but not with 1-acetoxy analogues, carbamate formation with 14 was difficult.4 A phenyl carbonate derivative of 14 was prepared, but it decomposed without forming a carbamate when treated with ammonia. 0 Abbreviations for microorganisms: E. coli = Escherichia coli, B. subtilis = Bacillus subtilis, K. pneumonia = Klebsiella pneumonia, Staph Smith = Staphylococcus aureus strain Smith, S. faecalis = Streptococcus faecalis, S. lútea = Sarcina lútea, Myco = Mycobacterium smegmatis.…”

“…Treatment of 14 with chlorosulfonyl isocyanate gave a vigorous reaction with possible formation of a chlorosulfonylcarbamate, but hydrolysis of the crude product was unsuccessful. Finally, an iV-methyl carbamate (15) was prepared by treating 14 with methyl isocyanate and triethylamine.…”

“…This possibility seems improbable in view of the report that the IV-methyl carbamate is somewhat less active than its unsubstituted analogue in related indoloquinones. 14 In Table II the abilities of these mitosenes and mitomycin A to induce the expression of -bacteriophage in Escherichia coli are presented. This assay has value in the preliminary screening of potential antitumor agents.…”