Anti-tumour heterocycles. Part xiv. A new route to pyrrolo-[3,2-f]indoles and the novel pyrrolo[3,2-f; 4,5-f′]diindole system

Abstract

Vilsmeier formylation of the dipyrrolylmethane 14a gave the 8-formylpyrrolo[3,2-f]indole 15. Alternatively, condensation of the pyrrole 1a with a variety of 2,3-unsubstituted pyrroles 16a–e in the presence of Montmorillonite K-10 clay gave, in general, the corresponding pyrrolo[3,2-f]indoles 19 and 21a–d. These pyrroloindoles were unambiguously structurally indentified by ¹H NMR spectra and NOE experiments. Amongst the by-products of the reaction were the corresponding pyrrolo[2,3-f]indoles, uncyclised 2-monosubstituted intermediate pyrroles and the 2,3-disubstituted derivatives. Similar results were obtained by replacing the ethyl ester 1a by the benzyl ester 1b.

The pyrrole 1a, with K-10 clay and the tetrahydroindole 24 gave only a very low yield of the spirocyclopentylpyrrolo[1,2-f]indole 25, but with the N-benzyl-4-oxotetrahydroindole 27b gave both the tetrahydropyrrolo[2,3-b]carbazole 28 and its [3,2-b] isomer 29 and other products.

The pyrrole 1a condensed with N-methoxycarbonylpyrrole 32 to give the pyrrolo[3,2-f]indole 33, its isomer 34, the monosubstituted intermediate 35 and the two products 36 and 37 resulting from disubstitution. Both of these (36 and 37) were cyclised with toluene-p-sulfonic acid to the novel pentacyclic pyrrolo[3,2-f; 4,5-f′]diindole 38.

Regiospecific hydrolysis and decarboxylation of the N-methoxycarbonylpyrroloindole 33 gave the 2,3-unsubstituted pyrrolo[3,2-f]indole 21k, which on Vilsmeier formylation gave the 8-formyl derivative 39b.