TY - JOUR
T1 - Synthesis of A-ring quinolones, nine-membered oxolactams and spiroindoles by oxidative transformations of 2,3-indolotriterpenoids
AU - Khusnutdinova, Elmira F.
AU - Kazakova, Oxana B.
AU - Lobov, Alexander N.
AU - Kukovinets, Olga S.
AU - Suponitsky, Kyrill Yu
AU - Meyers, Craig B.
AU - Prichard, Mark N.
N1 - Funding Information:
This work was supported by Federal programs No. AAAA-A17-117011910023-2 and AAAA-A17-117011910027-0. The NMR spectra were recorded at the Center for the Collective Use ‘Chemistry’ of the Ufa Institute of Chemistry of the Russian Academy of Sciences; X-ray structure investigation was carried out at the Center for Molecular Structure Studies at A. N. Nesmeyanov Institute of Organoelement Compounds. These studies were funded in whole or in part with Federal funds from the National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract HHSN272201100016I (MNP). EFK gratefully acknowledges the President of Russian Federation for a young scientist stipendium (SP-1507.2016.4).
Publisher Copyright:
© 2019 The Royal Society of Chemistry.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.1039/c8ob02624f
DO - 10.1039/c8ob02624f
M3 - Article
C2 - 30574983
AN - SCOPUS:85060056165
SN - 1477-0520
VL - 17
SP - 585
EP - 597
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
IS - 3
ER -