Synthesis, structure, and pharmacological activity of (7R,8S)-epoxy-(13R,17R)-trioxolane abietic acid

Abstract

The synthesis and X-ray diffraction established the structure of (7R,8S)-(see text for symbol)-(13R,17R)-trioxolaneabietic acid. Predicted by the computer system PASS antineoplastic activity and the ability to induce apoptosis, a mechanism of cell death, is correlated with experimentally shown cytotoxic activity against malignant cell line MeWo. Results of tests on animals have shown that abietic acid and its 9R,11S-epoxy-12R,15R-trioxolane derivative have anti-inflammatory and antiulcer activity in the absence of adverse effects on animal organisms.

Oxidation of Methyl 2-Cyano-3,4-seco-4(23)-Ene-Ursolate by Ozone

“…We found earlier that oleanolic acid methyl ester was oxidized by ozone to methyl 12-oxoolean-28-oate [23] whereas oxidation of the analogous ursolic acid derivative gave 12-oxo-11S,13R-oxetane on ring C [24]. Limitations of methods for synthesizing such chiral non-racemic oxetanes were noted [25].Considering the aforementioned examples and continuing research on oxidative transformations of plant terpenoids [11,12,14,17,18,[26][27][28], we decided to determine the direction of the oxidation by ozone of 2-cyano-3,4-seco-4(23)-ene ursolic acid methyl ester (1) and to compare the results with those published for oxidation of the analogous oleanolic acid derivative [23].Oxidation of 1 with two unsaturated bonds in the C-4(23) (ring A) and C-12(13) (ring C) positions by ozone in CH 2 Cl 2 formed the three 2-cyano-3,4-seco-4-oxo derivatives 12-oxours-11S,13R-oxetane (2, 68%), 11-oxours-12-ene (3, 12%), and 12-hydroxy-4,11-dioxours-12-ene (4, 8%) (Scheme 1). Thus, oxidation of methyl 2-cyano-3,4-seco-4(23)-ene ursolate by ozone was non-selective, in contrast with the oxidation of the analogous oleanolic acid derivative, which enabled selective transformations of rings A and C to be carried out [23].…”

“…Considering the aforementioned examples and continuing research on oxidative transformations of plant terpenoids [11,12,14,17,18,[26][27][28], we decided to determine the direction of the oxidation by ozone of 2-cyano-3,4-seco-4(23)-ene ursolic acid methyl ester (1) and to compare the results with those published for oxidation of the analogous oleanolic acid derivative [23].…”

“…3E,12D-Dihydroxyoleane-13E,28-lactone is a key intermediate in the synthesis of endothelin A receptor antagonists and a promising antidiabetic agent [5]. 12E-Hydroxyurs-11-ene-13E,28-lactone was produced by oxidative transformation of ursolic acid by ruthenium porphyrins and was active against A431 human skin cancer cells [5,6].The structures of the starting substrates are known to affect considerably the oxidation of triterpenoids [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. For example, the reactivities of oleanolic and ursolic acid derivatives were found to differ during oxidation by dimethyldioxirane although these triterpenoids differ only by the location of the methyl in ring E [21].…”

Synthesis and anticancer activity of quinopimaric and maleopimaric acids’ derivatives

“…The diterpenoids ability to induce apoptosis in different tumor cells is shown. 17,18 As a part of our program to investigate the plant terpenoids pharmacological potency, [6][7][8][19][20][21][22][23] especially to find cytotoxic agents among the levopimaric acid derivatives, we have realized the chemical transformations of levopimaric acid diene adducts with p-benzoquinone and maleic anhydride, resulting in more than twenty derivatives of quinopimaric and maleopimaric acids' with different double bonds, types of the E-ring and modification of the carbonyl-groups.…”

Synthesis and anticancer activity of aminopropoxytriterpenoids

“…As a part of our investigation program of the plant triterpenoids pharmacological potency (Kazakova et al 2010a, b;Kazakov et al, 2011;Kazakova et al 2011a, d;Kazakov et al, 2012;Kazakova et al 2013;Smirnova et al 2014Smirnova et al , 2015Tret'yakova et al, 2014;Yamansarov et al, 2015), we present here the synthesis of triterpenoids bearing cyanoethyl and aminopropoxy chains at the C-28 and C-3 or C-28 positions and their in vitro and in vivo anticancer activity. Fig.…”