Synthesis and Evaluation of the Cytotoxicity of Furanolabdanoids Containing a 3-Aminopropanoyl Substituent in the Furan Ring
YU. V. KHARITONOV1, D. A. PETROVA1, E. E. SHULTS1, M. A. POKROVSKII2, A. G. POKROVSKII2
1Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
2Novosibirsk State University, Novosibirsk, Russia
Keywords: diterpenoids, lambertianic acid, Mannich reaction, cytotoxicity
Pages: 715–723
Abstract
15-Acetyl- and 16-acetylfuranolabdanoids were synthesised by the acetylation of the methyl ester of lambertianic acid with acetic anhydride in the presence of Mg(ClO4)2 and used as starting compounds for the preparation of 15- or 16-(3-aminopropanoyl)methyllambertianates. The proposed approach involved silylation of 15-acetyl- or 16-acetylmethyllambertianate and the Mannich reaction of the resulting enol silyl ester with N,N-disubstituted methyleneiminium salts. The synthesized compounds possessed cytotoxicity on tumour cell lines CCRF CEM, MCF7 and PC-3 (MTT test). The compounds containing a 3-morpholinopropanoyl or 3-pyrrolidinopropanoyl substituent at the C-16 position of methyl lambertianate selectively inhibited the growth of human T-cell leukemia cells (GI50 was 5.8-6.1 μM) and exhibited cytotoxicity an order of magnitude higher than the parent compound lambertianic acid.
DOI: 10.15372/CSD2023521
EDN: HAUFLC
|
