The synthesis and properties of tricyclic diterpenoids containing a C-4 functionalized oxazole ring are reported. The reaction of 4-[5-(bromomethyl)oxazol-2-yl]-18-norisopimarane with sodium azide in the presence of hydrated copper sulfate and sodium ascorbate in DMF gave the corresponding azide, from which new diterpenoid derivatives containing a 1H-substituted 1,2,3-triazol-4-yl substituent were synthesized. Reduction of the azide produced the terpenoid 5-aminomethyloxazole. Reaction of 4-[5-(bromomethyl)oxazol-2-yl]-18-norisopimarane with methyl esters of amino acids in DMF in the presence of potash synthesized compounds with oxazole C-5 amino-acid substituents. Cytotoxicity of the new isopimaric acid derivatives gainst CEM-13, MT-4, U-937, MCF-7, and MDA-MB-231 human tumor cells was studied.
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Acknowledgment
The work was financially supported by grants from the RFBR (Project No. 17-43-543235) (p_mol_a) and the RSF (Project No. 18-13-00361). Biological studies were supported by Task No. 17.5484.2017/BY. Analytical and spectral studies were performed at the Chemical Research Common Use Center, NIOCh, SB, RAS.
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Translated from Khimiya Prirodnykh Soedinenii, No. 1, January–February, 2019, pp. 47–53.
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Gromova, M.A., Kharitonov, Y.V., Pokrovskii, M.A. et al. Synthetic Transformations of Higher Terpenoids. 37. Synthesis and Cytotoxicity of 4-(Oxazol-2-Yl)-18-Norisopimaranes. Chem Nat Compd 55, 52–59 (2019). https://doi.org/10.1007/s10600-019-02613-x
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DOI: https://doi.org/10.1007/s10600-019-02613-x