Lambertianic acid was selectively transformed at the carboxylic group. Synthetic methods for natural labdanoids, i.e., lambertianic acid methyl ester and lambertianol, were proposed. New N-containing diterpenoid derivatives with alkyl(aryl)amide, dialkylamide, hydrazide, N-hydroxycarbamoyl, and nitrile groups in the C-4 position of the labdane skeleton were synthesized via reactions of lambertianic acid chloride with aliphatic and aromatic amines, amino acids, hydrazine, and hydroxylamine. Compounds with higher cytotoxicity than lambertianic acid against MCF-7, HeLa, and HepG2 (MTT assay) human tumor cell lines were obtained. The IC50 value of the most active lambertianic acid N-hydroxycarbamoyl derivative was 15 μM (selectivity index >7).
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Acknowledgment
We thank staff of the Khimiya Service Center for Common Use, SB, RAS, for the spectral and analytical studies. The work was financially supported by a grant from the Russian Foundation for Basic Research and the Novosibirsk Region administration (Project No. 19-43-540003) and in the framework of a State Task (Projects Nos. 122040400030-8 and 122040400038-4).
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For No. 42, see the literature [1].
Translated from Khimiya Prirodnykh Soedinenii, No. 6, November–December, 2023, pp. 936–947.
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Kharitonov, Y., Antipova, V.I., Marenina, M.K. et al. Synthetic Transformations of Higher Terpenoids. 43. Synthesis and Cytotoxic Properties of New Lambertianic Acid Derivatives at the Carboxylic Group. Chem Nat Compd 59, 1109–1121 (2023). https://doi.org/10.1007/s10600-023-04206-1
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DOI: https://doi.org/10.1007/s10600-023-04206-1