An Efficient Oxyfunctionalization of Quinopimaric Acid Derivatives with Ozone

Abstract

An access to oxyfunctionalized quinopimaric acid derivatives is reported. The ozonolysis of methyl dihydroquinopimarate occurs through 1,2-cycloaddition of ozone to the bridging double bond followed by intermolecular rearrangements and formation of nontrivial 4β-hydroxy-4α,14α-epoxy-13(15)-ene derivative 2. The oxidation of methyl furfurilydene dihydroquinopimarate with ozone led to anhydride 5 and unexpected carboxymethyl substituted cyclopentane lactone 6. The structure of compound 6 was confirmed by X-Ray analysis of its methyl ester.

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].…”

Oxidative lactonization of oleanane and ursane acids by treating with ozone

“…For example, the oxidation of methyl ursolate with ozone proceeds with generation of 12-oxo-11S,13R-oxetane fragment in the cycle С [21], whereas the oxidation of methyl oleanate leads to methyl 12-oxooleane [22]. Different courses of oxidation processes of triterpenoids belonging to the α-and β-amirine series with reagents like m-chloroperoxybenzoic acid and HCOOH-H 2 O 2 underlie their separation in the form of oxyderivatives, because in plants these metabolites often accompany each other [3,23,24].In continuation of our research on the oxidative transformations of vegetable terpenoids [25][26][27][28][29][30][31] we investigated in the present study the oxidation of С 12 =С 13 bond of the ring С in oleanane and ursane acids with ozone involving the free carboxy group (oxidative lactonization).Oxidative lactonization of oleanolic acid at the treatment with ozone was investigated before in various solvents (ethyl acetate, N,N-dimethylacetamide-MeOH, СН 2 Сl 2 -MeOH) with generation of three types of structures: 12α,13α-epoxides, 12α-hydroxy- …”

“…In continuation of our research on the oxidative transformations of vegetable terpenoids [25][26][27][28][29][30][31] we investigated in the present study the oxidation of С 12 =С 13 bond of the ring С in oleanane and ursane acids with ozone involving the free carboxy group (oxidative lactonization).…”