Ursolic acid structure

Figure 5.1 Structures of the pure triterpenes studied by GALDI MS hydroxydammarenone (20 hydroxydammar 24 en 3 one) 1, oleanolic acid (3 hydroxyolean 12 en 28 oic acid) 2, oleanonic acid (3 oxoolean 12 en 28 oic acid) 3, 18(3 glycyrrhetinic acid ((3(3,18(3,20(3) 3 hydroxy 11 oxoolean 12 en 29 oic acid) 4, uvaol (urs 12 en 3,28 diol) 5, ursolic acid (3 hydroxyurs 12 en 28 oic acid) 6, and ursonic acid (3 oxours 12 en 28 oic acid) 7...

Methylation at C-4 of sterol nucleus was one of the other factors affecting activity enhancement. Thus, in general, 4-methylsterols (14,15) and 4,4-dimethylsterols (8,13) exhibited higher activity than 4-desmethylsterols. A similar structure-activity relationship was observed also in the HHPA-induced inflammation on mouse ear [35]. Whereas cholesterol (7) did not show inhibitory activity, several 4,4-dimethylcholestane derivatives, 0-12, exhibited activity. 4,4-Dimethylcholestane-3a,5a-diol (12) was the most potent inhibitor its activity was comparable to that of ursolic acid (210) [35]. Compound 12 reduced also the inflammation induced by teleocidin B (3), one of the indole alkaloid-type of tumor promoters [53]. 

Triterpenic Acids. The following pentacyclic mono- and dihydroxy triterpenic acids are present in virgin olive oil (35, 43, 44) 3p-hydroxy-17-carboxy-5-12-olea-nene (oleanolic acid) 3 3,2a-dihydroxy-17-carboxy-5-12-oleanene (maslinic acid) 3p-hydroxy-17-carboxy-8-12-ursene (ursolic acid) 2a,3p-dihydroxy-17-carboxy-5-12-ursene (2a-hydroxyursolic acid) and deoxyursolic acid (structure not fully elucidated). 

Preliminary structure-activity relationship studies on triterpene saponins have shown the best activity against HSV-1, -2, adenovirus (AD-2), polyovirus (PV-2) and VSV for saponins having as aglycones ursolic acid, glycyrrhetinic acid, hederagenin and oleanolic acid [152],... 

In connection with the work on the relationship between chemical structure and anti-inflammatory activity, the effect of ursolic acid, betulin, betulinic acid and erythrodiol on a system of chronic dermal edema and cellular proliferation caused by repeated administration of TPA has recently been examined [89], This experimental model of chronic inflammation has considerable selectivity for corticosteroids and leukotriene synthesis inhibitors. Erythrodiol and ursolic acid were significantly effective and also reduced the neutrophil infiltration detected by MPO activity. The lupane derivatives, betulin and betulinic acid, despite their possible steroid-like mechanism of action [47], were not effective in the chronic model. This result could mean that a six-member E ring of the pentacyclic structure is necessary for the activity against a multiple dose of TPA. The data confirm that a hydroxyl group at the C-28 position is important for the activity, as is also true in the case of erythrodiol, and it may explain the anti-inflammatory effect of this compound in each of the methods. 

In order to obtain more information on the chemical reactions involved in the LOX inhibitory effect of triterpenes, ursolic acid and its analogues (uvaol, oleanolic acid and methyl ursolate) were studied on LOX activity. The best inhibitors of soybean 15-LOX were ursolic and oleanolic acids, with IC50 values of 0.175 and 0.265 mM, respectively. These results showed that the carboxylic group in the position 28 in ursolic acid is implicated in the inhibition of LOX activity because methylation of this functional group abolished it. Other structural features of ursolic acid are also relevant for its inhibitory effect, for oleanolic acid is less active than ursolic acid, and yet they only differ in the position of one methyl group (at C-20 instead of C-19) [101]. 

Remarkably few triterpenes have been isolated from Eremophila species. Oleanolic acid and ursolic acid were isolated from E. caerulea (134) and 3-ept-oleanolic acid from E. platycalyx (16). Two unusual triterpenes (218 and 219) have been isolated from the wood oil of Eremophila mitchelli. Their structures were determined from a combination of spectroscopic techniques, aided by an X-ray diffraction study of the tetrahydro-derivative (220) of the dione (218). The... 

Triterpenic and steroidal compounds were also isolated from Teucrium species. Common triterpenic acids such as ursolic acid, oleanolic acid and small amounts of micromeric acid were isolated from T.fruticans [81] while a-amyrin, lupeol, sitosterol and stigmasterol were present in T. divaricatum subsp. villosum [75]. Two new steroidal compounds SP-hydroxy-stigmast-24(24i), 25-dien-242-al (157) and 3P-hydroxy-24a-ethylcholesta-5, 25-dien-7-one (158) were isolated together with two known compounds 24a-ethylcholesta-5, 25-dien-3P-ol (159) and sitosterol from the aerial parts of T.chamaedrys subsp. chamaedrys [82]. The plant also yielded a-amyrin and ursolic acid. The structures of the new steroidal compounds were established by NMR techniques and by comparison of similar known compounds (Table 24). 

The ethanol extract from the fruit of Randia siamensis after separation by column chromatography yielded four components ursolic acid (1), pseudoginsenoside-RPi (2), pseudoginsenoside-RTi (3) and siamenoside (4). 1 is a conunonly occurring triterpenoid acid while 2 and 3 are saponins which were first isolated from Panax (Araliaceae) species and were identified by Tanaka et al. (198S). The major component isolated in our study, oleanolic acid glycoside 3, has since been reported to be present in additional species (Morita et al., 1986 Shukla and Thakur, 1988 Shukla, 1989 Ida et al., 1994 Sakai et al., 1994). In the structural elucidation of the four components from R. siamensis, NMR spectroscopy was foimd to be... 

Some T. have major physiological significance. Thus, lanosterol is converted biosynthetically to cholesterol, the precursor of all steroid hormones, bile acids, and vitamin D3. In fungi, lanosterol is converted to er-gosterol (see sterols), an essential component of the fungal cell membrane. Plant cell membranes also incorporate steroids (phytosterols). In prokaryotes, the hopanoids take over the functions of steroids in the cell membranes. As a component of animal and plant waxes T. strengthen the structures. They protect the plant surface from desiccation and attack by microorganisms (e.g., betulin, lupeol, oleanolic acid, and ursolic acid). 

Ibragimov AYa, Khazanovich RL (1972) Ursolic acid from Agrimonia asiatica. Chem Nat Compd 8(3) 390-391 Ibragimova MU, Israilov lA, Yunusov MS, Yunusov SYu (1974) Alkaloids of Fumaria vaillantii structure of vadlantine. Chem Nat Compd 10(4) 481 82... 

Ursolic acid a simple unsaturated pentacylic tri-terpene carboxylic acid, M, 456.71, m.p. 292°C, [d o + T2° (CHCI3). U.a. is a structural derivative of a-Amyrin in which the 28-methyl group is replaced by a carboxyl group (see Amyrin). It occurs widely in plants as the free acid, esterified, or as the aglycon of triterpene saponins (see Saponins), e.g. in the wax layer of apples pears and cherries in the skin of bilberries and cranberries, and in the leaves of many members of the Rosaceae Oieoceae and Labiatae. 

The studies with a goal to explore the variability of biological responses from the perspective of sample purity have been performed by Jaki et al For this purpose nine different samples of the pentacyclic plant triterpene ursolic acid with purity certifications were obtained, and their purity was independently assessed by means of quantitative HNMR. Biological evaluation consisted of determining MICs against two strains of virulent Mycobacterium tuberculosis and IC50 values in Vero cells. Ab initio structure elucidation provided unequivocal structural confirmation and included an extensive H NMR spin system analysis, determination of nearly all /hh couplings and the complete NOE pattern, which led to a revision of earlier reports. 

The triterpene sapogenins betulinic acid, oleanolic acid and ursolic acid show cytotoxic and anti-inflammatory effects, and based on their structures novel chemopreventive and anticancer agents are being developed (Liby et al., 2007). A derivative of betulinic acid, beviri-mat, is the first member of a new class of anti HIV therapeutics, maturase inhibitors. These... 

Most of the 20 odd triterpenes that have been structurally determined are derived from pentacyclic hopane (94). The exceptions are friedelin (95), epifriedelanol, taraxerene, ursolic acid, and diacetyl pyxinol. 

Figure 1. Structure of rosemary phytochemicals, (A) carnosic acid (B) carnosol (C) rosmarinic acid (D) ursolic acid.

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