Lupane Group

A second member of the A(l),28-bisnorlupane series, deoxyemmolactone (150), has been found in the bark of Alangium villosum. The position of the trisub-stituted double bond remains in doubt. Jingullic acid, from Emmenospermum alphitonioides, has been assigned the structure (151). It was correlated with the mercuric acetate oxidation product (152) of dihydroceanothic acid (153). 

Degradative studies have shown that mercuric acetate oxidation of acetyl-betulinic acid (154) and dihydroceanothic acid (153) results in the formation of the C-28 — C-19 lactones (155) and (152) respectively. The configuration of the hydrogen at C-18 in these compounds is a. Under similar conditions betulin (156) is transformed into the ether (157). The product of mercuric acetate oxidation of lupenyl acetate (158) is 3j5-acetoxylupa-18,20(29)-diene (159) and not the I3(18),20(29)-diene as previously suggested. Treatment of the ring a seco- 

Halsall and his colleagues have elucidated the structures of a number of the minor products of ozonolysis of methyl acetylbetulinate (162). In addition to the expected nor-ketone they obtained the two trisnor-compounds (163) and (164), the Baeyer-Villiger product (165), and the bisnor-acid (166). These results are rationalised in terms of three different decomposition mechanisms for the ozonide 

X-Ray analysis of the new triterpenoid (134) from Emmenospermum pancherianum (Rhamnaceae) indicated that the isopropenyl group has the unusual P-configur-ation.43 Subsequent reinvestigation of emmolactone82 by X-ray analysis showed that it also has a p-isopropenyl group, and its structure is therefore revised to 

Details have appeared of the synthesis91 and rearrangement92 of 3a,4a- and 3p,4p-epoxy-D A-friedo-18p,19a-H-lupanes (seeVol. 11, p. 123). Wagner-Meerwein type rearrangements of some lupane derivatives have been studied.93 The 13C n.m.r. spectra of some lupanes have been reported.94 

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 

Acid-catalysed isomerization of the olefins (153)—(155), obtained on decarboxylation of lupan-28-oic acid, resulted in the formation of the lup-17-ene derivative (156) with inversion at C-19 and not 28-norlup-13(18)-ene (157) as previously suggested.Further studies have been reported on a series of lupan-12-one and 29-hydroxy-30-norIupan-20-one (158) derivatives. The nitrone (159) and the N-hydroxy-Iactam (160) were produced on irradiation of 3 -acetoxy-28-nitrosyloxylupane (161).  

Protiva, F. Turecek, and A, Vystrcil, Coll- Czech. Chem. Comm., 1977,42, 140. 

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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... 

In a similar study of the ozonolysis of betulin diacetate, Vystrcil and Budesinsky obtained inter alia compounds (168), (169), and (170). Continuing their studies of epimerisation at C-19 in the lupane series, these authors have reported the formation of the lactone (171) by acid equilibration of the bisnor-acid (172). Performic acid oxidation of the isopropenyl group in a number of lupene derivatives has been described. Most of the products can be rationalised by assuming the rearrangement of an initially formed epoxide. 

A series of lupane caffeoyl esters have been isolated from Celastrus stephanotifolius and Hippocratea volubilis by Chen and coworkers [43] and our research group [44]. 

From the root bark of H. volubilis, volubilide (51) was isolated. This unusual compound has a structure based on two monomer units from abietane and lupane di/triterpene skeletons. From its HREIMS, H, 13C-NMR and X-ray data the molecular formula C50H74O5 was obtained for (51). From the l3C-NMR data and 2D NMR experiments, the C-30 unit was identified as a lupane derivative with a 30-21a lactone group, related to ochraceolide A [65]. 

The main kind of anti-inflammatory triterpenes isolated have oleanane, ursane, taraxastane, lupane and lanostane skeletons (Table 1). Some minor compounds such as hopane are included in other structural groups. Other anti-inflammatory triterpenes like the different cucurbitacins are not included in this review because of their high toxicity. 

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. 

Collagenase production and release are partly responsible for the joint destruction that characterises human rheumatoid arthritis. Triterpenes from the lupane and a-amyrin groups have been studied in vitro to examine their effects on the release of the arthritic joint degradative enzyme collagenase using the rat osteosarcoma. This test and the rat synovial granuloma of adjuvant arthritis are similar both models are based on connective tissue tumours with bone-invasive properties. The pentacyclic triterpenes assayed have been shown to possess general antiproteolytic effects that can explain the anti-arthritic effects in adjuvant arthritis in rats [71,103]. 

Both the mixed stems and stem bark, and the stems CHCls-soluble extracts of L. wallichii Kurz, were found to display significant inhibitory activity in a famesyl protein transferase (FPTase) assay system. It has been suggested that inhibitors of this enzyme may be considered as potential anticancer agents for tumors in which products of the ras oncogene contribute to transformation. The bioassay directed fractionation of the two active extracts [213] led to the isolation of the known lupane lactones, ochraceolide A (128), ochraceolide B (129), and the new compound dihydroochraceolide A (135), among other known triterpenes. The structure of 135 was confirmed by reduction of 128, Fig. (37) and the stereochemistry to the epoxide group of 129, not determined when this compound was first isolated from K. ochracea [211], was established by preparation of both epoxide isomers, 129 and the new semisynthetic derivative, 20-epi-ochraceolide B (136) from 128. 

The 3p-hydroxy triterpenes of the oleanane, ursane and lupane series have been converted to the 2-deoxy- and 2,6-dideoxy-a-L-arafcmo-hexopyranosyl derivatives by addition processes applied to L-glucal and L-rhamnal. p-Gluco-sides of diol 78 (R = R = H) have been made with the sugar bonded separately to each of the hydroxyl groups. ... 

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