Synthesis of A-ring quinolones, nine-membered oxolactams and spiroindoles by oxidative transformations of 2,3-indolotriterpenoidsElectronic supplementary information (ESI) available: 1H, 13C NMR spectra of synthesized compounds (PDF). CCDC 1852656. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c8ob02624f

• Main Authors: Khusnutdinova, Elmira F, Kazakova, Oxana B, Lobov, Alexander N, Kukovinets, Olga S, Suponitsky, Kyrill Yu, Meyers, Craig B, Prichard, Mark N
• Format: Article
• Language: English
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c8ob02624f

This paper describes an access to new nitrogen-containing heterocyclic triterpenoids by the reaction of 2,3-indolotriterpenoids with ozone and dimethyldioxirane. The oxidation of indolo-fused 28-oxo-allobetulin or methyl platanoate with ozone led to a mixture of a quinolone as the major product and a nine-membered 2,3-seco-2-oxolactam and three different types of spiroindoles as byproducts. The formation of quinolone and 2,3-seco-2-oxolactam derivatives could be explained by the standard 1,3-dipolar cycloaddition of ozone to the C2(3)-double bond of the triterpene core similar to the products observed in the ozonolysis of indoles in the Witkop-Winterfeldt oxidation (WWO). The formation of spiroindoles was unexpected and could be explained through the 1,2-cycloaddition of ozone to the C2(3)-double bond with consecutive intramolecular rearrangements of the 2,3-epoxy-intermediate. These spiroindoles seem to be novel structures observed in the WWO reaction. The formation of only two isomeric triterpene spiroindolinones was achieved by the oxidation of 2,3-indolo-28-oxo-allobetulin with dimethyldioxirane that could be explained by the rearrangement of the 2,3-epoxy-intermediate. 19β,28-Epoxy-18α-olean-28-oxo-2-nor-2,3-4′(1 H )-quinolone was the most active against HPV-11 with EC 50 0.45 μM and SI 50 322 in a primary assay and SI 90 < 10 against HPV-16 in a secondary assay. The oxidative transformations of indolotriterpenoids have great potential for further modifications towards the preparation of new biologically active compounds. An access to new antiviral A-ring quinolones, oxolactams and spiroindoles by oxidation of 2,3-indolo-triterpenoids with ozone and dimethyldioxirane is reported.