Mitosenes, structure

Scheme 7.11 shows the product structures resulting from the dithionite reduction of a simplified version of WV-15. The symmetric sulfite diester was extracted from the reaction mixture with methylene chloride. The isolation and characterization of the sulfite diester confirmed that this species can form in dithionite reductive activation reactions and provided the chemical shift for the 10a-13C center of a mitosene sulfite ester (49.37 ppm). The aqueous fraction of the reaction contained the mitosene sulfonate and trace amounts of Bunte salt, based on their 13C chemical shifts. 

For synthetic chemists the structure of mitomycins presents a formidable challenge. This is mainly because these pyrrolizine derivatives undergo facile elimination of methanol to give unstable aziridino mitosenes (216) which easily react to give solvolyzed products. Reduction of the quinone group gives even more unstable hydroquinones (217). 

Jones GB, Moody CJ (1989) Structurally modified antitumor agents. Part 1. Synthesis of cyclopropapyrrolo[l,2-a]indoles related to mitosenes by intramolecular cycloaddition. J Chem Soc Perkin Trans 1 2449-2454... 

In this review, the trivial names mitosane and mitosene [14] (Fig. 1) will be used to describe various mitomycin structures. For example, mitomycin C is 7-amino-9a-methoxymitosane. It should be noted that the numbering of a mitosane differs from the systematic numbering used in Chemical Abstracts for azirino[2, 3 3,4]pyrrolo[l,2-a]indoles, wherein the aziridine nitrogen is the starting point. 

H-NMR clarified the structure of the mitosene moiety but gave very limited information on the guanine portion due to the lack of usable proton signals other than 8 -H. The use of UV in determining the point of attachment of the mitosene to the guanine moiety was therefore explored. The UV spectra of alkylated... 

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