Synthesis and Unexpected Oxidization of the Tricyclic Core of Ugibohlin, Isophakellin, and Styloguanidine

Abstract

A series of 4-substituted 5,6,7,9-tetrahydropyrrolo[2,3-f]indolizin-9-ones, representing the tricyclic core skeleton of ugibohlin, isophakellin, and styloguanidine, were synthesized via an intramolecular Vilsmeier-Haack reaction. This reaction allows the chemoselective C-C bond formation between the pyrrole C3 and proline C5 of N-[(pyrrol-2-yl)carbonyl]prolinamides to construct the B-ring without the protection of the pyrrole nitrogen. Unexpected oxidizative property of the tricyclic core skeleton was observed, which could illuminate understanding of the biological formation of these marine secondary metabolites.

Synthesis of 3,3-disubstituted-2,3-dihydroazanaphthoquinones via simultaneous alkyne oxidation and nitrile hydration of ortho-alkynylarenenitriles

“…It is interesting to note that the functional group pattern (ketone, 3°alcohol and amide functional groups in a six-membered ring) found in the aminols 4 is present in the precursor used in the total synthesis of the alkaloid, chilenine 23 and also in the tricyclic core of secondary metabolites ugibohlin, isophakellin and styloguanidine. 24 To prove the point that the aminols 4 would behave like respective azanaphthoquinones in their reactions, the nucleophilic addition reactions of 4a were investigated. We reasoned that the dehydration and the nucleophilic addition would be assisted by acid catalysts, because Nicolaou et al have used triflic acid in the case of 3-aryl-3-hydroxyoxindoles for generating an all-carbon quaternary center at C-3 by Friedel-Crafts alkylation with aromatics.…”

Muscarine, imidazole, oxazole and thiazole alkaloids

“…29 The tricyclic core 4substituted 5,6,7,9-tetrahydropyrrolo[2,3-f]indolizin-9-one 42 of alkaloids ugibohlin 39, dibromoisophakellin 40, and styloguanidine 41 was synthesized via an intramolecular Vilsmeier-Haack reaction. 30 An unexpected oxidation mechanism of this type of tricyclic core skeletons was observed, which provided additional information for the biological synthesis of these secondary metabolites.…”