Lupane triterpenoids

In addition to H and NMR analysis, TLC coupled in an offline manner with electrospray mass spectrometry (ESI-MS) and high-resolution ESI Fourier transform ion cyclotron resonance (FTICR) MS for isolation and characterization of two novel lupane triterpenoids from Paullinia pinnata L. 6P-(3 -methoxy-4 -hydroxybenzoyl)-lup-20(29)-ene-one and 6P-(3 -methoxy-4 -hydroxybenzoyl)-lup-20(29)-ene-ol, which are suspected to play a crucial role in the plant s wound healing effects [32]. The extract from Paullinia pinnata L. was subjected to an exhaustive isolation procedure starting with two consecutive column chromatography purifications on silica gel different ratios of chloroform-methanol were used as eluent. The triterpenoid-containing fraction was purified on preparative silica gel TLC plate with chloroform-methanol (9 1, v/v) as a developing solvent. The two resulting lupane bands were finally submitted to MS analyses. 

Annan, K. and Houghton, P.J. 2010. Two novel lupane triterpenoids from Paullinia pinnata L. with fibroblast stimulatory activity, J. Pharm. Pharmacol., 62 663-668. 

Betulinic acid (51) and its close structural anolog, betulin (52), are lupane triterpenoids widely distributed in the plant kingdom, with the latter especially abundant in the bark of the white birch tree [133], Betulin can serve as the semi-synthetic precursor of betulinic acid, which is considered biologically more active than betulin. Important biological activities attributed to betulinic acid and its derivatives, are anti-EHV activity and selective cytotoxicity against melanoma cancer cells [133-135]. Betulinic acid can indnce apoptosis by acting on the mitochondria of various tumor cells. This compound is currently under phase I/n clinical trials launched by National Cancer Institute (NCI) as a chemotherapeutic agent for the treatment of dysplastic melanocytic nevi, which are considered associated with cutaneous melanomas [136]. 

The plant is known to produce norbisabolane diterpenes, including phyllanthusols A and B, which are both cytotoxic (36). From the bark, pentacyclic triterpenoids, phyl-lanthol, and olean-12en-3[3-ol (p-amyrin) have been isolated (37). Note lupane- and oleanane-type triterpenoids isolated from the bark of Phyllanthus flexuosus, such as olean-12-en-3 (3,15 a-diol, olean-12-en-3 [3,15 a,24-triol, lupeol, and betulin inhibited the enzymatic activity of topoisomerase II activity with IC50 values in the range of 10 to 39 p.M (38). 

Frankincense, also known as olibanum, is obtained from trees belonging to the genus Boswellia (Burseraceae family). It is one of the best-known ancient plant resins. The ancient Egyptians were the first to use it as incense in embalming practices and in the preparation of medicines, cosmetics and perfumes, and today it is still used therapeutically. It contains pentacyclic triterpenoids belonging to oleanane, ursane or lupane type molecules and in particular of a- and p-boswellic acids, and their O-acetates [104 111], 11 -Oxo-p-boswellic acid and its acetyl derivative, identified in several Boswellia species, are also diagnostic for frankincense [112]. 

Betulin and lupeol, together with low amounts of lupenone, betulone and betulinic acid, are characteristic of birch bark [87,153 157]. All these compounds are pentacyclic triterpenoids with a lupane skeleton. In addition to triterpenoids, birch bark contains high amounts of a lipid material, called suberin [158]. 

Regert et al. studied [9] a series of 30 Neolithic hafting adhesives from lake dwellings at Chalain (France) using an analytical procedure based on GC/MS analysis involving solvent extraction (dichloromethane) and trimethylsilylation. In the majority of the samples a series of triterpenoid compounds with a lupane structure was clearly identified on the basis of their TMS mass spectra. In particular, the presence of betulin, betulone, lupenone, lupeol and lupa-2,20(29)-dien-28-ol allowed birch bark tar to be identified. In other samples the co-occurrence of other plant biomarkers such as a-amyrin,(3-amyrin... 

Triterpenoid saponins are synthesized via the isoprenoid pathway.4 The first committed step in triterpenoid saponin biosynthesis involves the cyclization of 2,3-oxidosqualene to one of a number of different potential products (Fig. 5.1).4,8 Most plant triterpenoid saponins are derived from oleanane or dammarane skeletons although lupanes are also common 4 This cyclization event forms a branchpoint with the sterol biosynthetic pathway in which 2,3-oxidosqualene is cyclized to cycloartenol in plants, or to lanosterol in animals and fungi. 

The structure of benulin (134), a lupene hemiacetal from Bursera arida, has been confirmed by X-ray analysis. An investigation of several Senecio species has resulted in the isolation of a series of lupane derivatives which include the acids (135), (137), and (139), the corresponding aldehydes (136), (138), and (140), the ketone (141), and betulonic acid. Three more triterpenoids (142)—(144) have... 

Esterification with a fatty acid or with ferulic acid at C-3 of triterpene alcohols exerted almost no influence on the activity as has been observed with lupane- (264/265) and cycloartane- (66/67, 72/73) type compounds and a C-3 monohydroxy triterpenoid (264/266). However, esterification at C-3 with a fatty acid reduced the inhibitory activity of some dihydroxy triterpenoids (138/139,140 202/203, 204 230/231 232/233, 234). 

Induction of epidermal ODC is a characteristic biochemical alteration elicited by TPA and may be representative of the effects of phorbol esters with strong tumor promoting activity [81]. A single application of TPA (5 pg) resulted in a substantial and transient increase of epidermal ODC activity in mice with a peak at about 4 h after TPA treatment, and the induction was potently inhibited by treatment (5 pM) of the mouse skin with sitosterol (33, 65% inhibition) and three lupane type triterpenoids betulin (255 79%), betulinic acid (257 89%), and lupeol (264,96%) [30]. The inhibitory effect on TPA-induced ODC activity was further reported for ursolic acid (210 45% inhibition at 2.0 pM/5nM of TPA) [31]. 

Plant-derived triterpenoids are overtly abundant in sediments from the late Mesozoic onwards. These include oleanane (61), lupane (62), and taraxastane (63). There is a clear relationship between these compounds and triterpenoid precursors such as /3-amyrin (64)... 

Rao et al. (52) isolated the novel triterpenoid, hyptadienic acid from the aerial part of H. suaveolens. This was the first report of a naturally occurring A-ring contracted triterpene outside the lupane series. Triguna et al. (67) isolated the new natural triterpenoid, 3y -hydroxylup-12-en-28-oic acid, from the roots of H. suaveolens in addition to a- and yff-amyrin. 

The interesting biological properties shown by many saponins, coupled with improvements in spectroscopic methods of structure determination have led to the increased study of this class of compound. The following papers deal with saponins and prosapogenins which are based on known triterpenoids of the following groups dammarane-euphane,158 lupane,159 oleanane,160 and ursane.161... 

Triterpenoids are widely distributed throughout the plant kingdom. Oleananes and ursanes, which often occur together, and lupanes are found... 

Widespread reports indicate that, in addition to their anti-inflammatory role, triterpenes have other activities. Triterpenoids have been found to possess cytotoxic, antimicrobial and interesting effects on metabolism. Triterpenoids with antitumour activity include oleanane, lanostane, lupane, friedelane, hopane and quassionoid types. Glycyrrhetinic acid has been described as an antiviral, hypolipidemic and anti-atherosclerotic agent. Cucurbitacins B and E, and oleanolic acid possess a potent protective action on the liver, and ganoderic acid and its derivatives have been shown to be inhibitors of cholesterol biosynthesis. Lanostane derivatives, like suberosol, have also been found to inhibit HIV replication in H9 lymphocytes [1,3]. 

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