Synthesis of A-ring quinolones, nine-membered oxolactams and spiroindoles by oxidative transformations of 2,3-indolotriterpenoids

Elmira F. Khusnutdinova, Oxana B. Kazakova, Alexander N. Lobov, Olga S. Kukovinets, Kyrill Yu Suponitsky, Craig B. Meyers, Mark N. Prichard

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8 Scopus citations

Abstract

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′(1H)-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.

Original languageEnglish (US)
Pages (from-to)585-597
Number of pages13
JournalOrganic and Biomolecular Chemistry
Volume17
Issue number3
DOIs
StatePublished - 2019

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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