Conjugates of betulinic, oleanolic, ursolic, and glycyrrhetic acids and several of their derivatives with the antituberculosis drug isoniazid and 3-and 4-pyridinecarboxaldehydes were synthesized.Betulinic, oleanolic, ursolic, and glycyrrhetic acids have been successfully modified in the last decades to produce new biologically active compounds [1-6] of various structures including hydrazides and hydrazones [4] with antiviral and antitumor activity. It was shown recently that functionalization of the diterpenoid oxo-acid isosteviol by N-containing groups increased its antituberculosis activity, reducing the minimal inhibitory concentrations (MIC) from 50 to 1.5 Pg/mL [7]. Because antituberculosis activity is also typical of triterpenoids, namely betulin [8] and betulinic [8][9][10][11], oleanolic [10-13], and ursolic [10,14] acids, it seemed interesting to perform an analogous investigation of the isoprenoid series by studying the effect of their functionalization by the same N-containing groups that were used for isosteviol [7].Herein we report the synthesis of conjugates of betulinic, oleanolic, ursolic, and glycyrrhetic acids and 28-oxoallobetulone with the antituberculosis drug isoniazid (4-pyridinecarboxylic acid hydrazide) and 3-and 4-pyridinecarboxaldehydes.Mixed hydrazides 7-9 (Scheme 1) were synthesized via reaction of acid chlorides 4-6, which were prepared from triterpene acids 1-3, with isoniazid by refluxing in CHCl 3 in analogy with the previous work [15]. The target products were isolated by column chromatography in 71-77% yields. The PMR spectra turned out to be sufficiently characteristic to establish their structures. They showed resonances for amide protons at weak field (G 6.35 ppm, 8.15, 9.00-9.25, 10.15-10.90). Doubled resonances for the amide protons were noted in 7. This indicated that conformational equilibrium around the C(O)-N bond was occurring in solution. Protons of the pyridine rings of 7-9 appeared as doublets at G 7.56-7.68 (H-3c, H-5c) and 8.50-8.67 (H-2c, H-6c) ppm. 13 C NMR spectra exhibited resonances for C-28 (C-30) and C-7c at G 174.3-176.3 and 161.4-163.7 ppm.
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