The chemical and biological potential of C ring modified triterpenoids

Siewert, Bianka; Wiemann, Jana; Köwitsch, Alexander; Csuk, René

doi:10.1016/j.ejmech.2013.11.025

Cited by 52 publications

(35 citation statements)

References 55 publications

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“…A previous study states that the treatment of oleanolic acid (1) or methyl maslinate (4) with MCPBA does not produce epoxy derivatives (Siewert et al, 2014). Therefore, from maslinic acid (2) and through the 12a-bromo-28,13b-olide derivative (12), we produced the 12,13-epoxy derivative (13) (Fig.…”

Section: Biotransformation Of Compound 13mentioning

confidence: 89%

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Biotransformation of oleanolic and maslinic methyl esters by Rhizomucor miehei CECT 2749

et al. 2015

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Section: Biotransformation Of Compound 13mentioning

confidence: 89%

“…This compound (11) was semi-synthesised from the 2a,3b-diacetyl derivative of methyl maslinate with MCPBA, which exhibited moderate cytotoxic activity on different cancer-cells lines (Siewert et al, 2014). The formation of this compound (11) could be explained (4) with Rhizomucor miehei.…”

Section: Biotransformation Of Methyl Maslinate (4)mentioning

confidence: 99%

Biotransformation of oleanolic and maslinic methyl esters by Rhizomucor miehei CECT 2749

et al. 2015

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“…Cytotoxicity of oenanthotoxin (1) and derivatives 13, 15-21 was determined using the photometric sulforhodamine B assay [40][41][42][43] employing six different human cancer cell lines and non-malignant mouse fibroblasts (NIH 3T3) for comparison. The results of these assays are compiled in the Table 1.…”

Section: Biologymentioning

confidence: 99%

Chemoenzymatic synthesis and cytotoxicity of oenanthotoxin and analogues

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Siewert

et al. 2015

Bioorganic & Medicinal Chemistry

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“…Ursolic acid derivatives with a 12-hydroxy-11-oxo-12-ene fragment in ring C had not been described previously. After our research was completed, the formation of this fragment via oxidation by SeO 2 of a 12-oxo oleanane derivative was reported [21].…”

mentioning

confidence: 95%

“…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]. Proposed schemes for separating mixtures of ursolic and oleanolic acids, which occur together in natural sources, were based on the inertness of the C-12(13) unsaturated bond of the former to the action of m-CPBA and HCOOH/H 2 O 2 [21,22]. 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].…”

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confidence: 98%

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

et al. 2014

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oxetane. The last was formed by oxidation of intermediate 12-oxoursolate. Ozonolysis of the ursolic acid derivative with two unsaturated bonds in the C-4(23) and C-12(13) positions was non-selective, in contrast with that reported previously for an analogous oleanolic-acid derivative.The triterpenoids oleanolic and ursolic acids are widespread in the plant world and exhibit various biological activities including antidiabetic, anticancer, antiviral, etc. [1][2][3]. Oxygenation of ring C is an important technique for modifying their structures in order to prepare new biologically active compounds. Examples include the synthesis from oleanolic acid of bardoxolone methyl (2-cyano-3,12-dioxooleane-1(2),9(11)-dien-28-oic acid methyl ester), which passed phase I clinical trials for treating cancer and phase II for treating chronic kidney disease in type 2 diabetes patients [4]. 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]. Proposed schemes for separating mixtures of ursolic and oleanolic acids, which occur together in natural sources, were based on the inertness of the C-12(13) unsaturated bond of the former to the action of m-CPBA and HCOOH/H 2 O 2 [21,22]. 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].

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The chemical and biological potential of C ring modified triterpenoids

Cited by 52 publications

References 55 publications

Biotransformation of oleanolic and maslinic methyl esters by Rhizomucor miehei CECT 2749

Biotransformation of oleanolic and maslinic methyl esters by Rhizomucor miehei CECT 2749

Chemoenzymatic synthesis and cytotoxicity of oenanthotoxin and analogues

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

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