Synthesis of Mitomycin C Analogues. 1. Introduction of the Urethane Function at C-10 of the Pyrrolo[l, 2-a ]indole Skeleton

α-(Alkoxymethylene)-2-(1-pyrrolidinyl)benzeneacetonitriles 5b-e, prepared by condensation of 2-(1-pyrrolidinyl)benzeneacetonitrile with ethyl formate and subsequent alkylation of the sodium salt formed, cyclize thermally to the trans- and cts-9-(alkoxymethyl)pyrrolo[l, 2-a] indoles 6b-e and 7b-e, respectively. Treatment of the sodium salt of 5a with acetyl chloride or acetic anhydride affords the 1-alkylindoles 8a and 8b, respectively. The mechanisms of both types of reaction, which are examples of the “tertiary amino effect”, are discussed. The CH₂OR group of the pyrrolo[l, 2-a]indoles 6b, d, e and 7b, d, e is deprotected, dependent on the nature of R, by boron tribromide (R = CH₃), hydrobromic acid in acetic acid, and subsequent hydrolysis of the acetate formed (R = CH₂Ph) and by concentrated hydrochloric acid in methanol (R = CH₂OCH₃) to give the corresponding alcohols 6a and 7a, respectively. Treatment of the pyrrolo[l, 2-a]indole 7b with sodium in liquid ammonia yields a mixture of isomers of the 9-methylpyrrolo[l, 2-a]indole 12b; in addition to the cyano group at C-9 also the methoxy group has been removed. Under these conditions the alcohol 7a affords a mixture of 12b and the decyanated alcohols cis- 12c and trans- 12c. The alcohols 7a and trans- 12c are transformed to the corresponding urethanes 7g and 12d, respectively.