Triptolides

In China, the plant is used to treat rheumatic inflammation. The anti-inflammatory property is substantiated, and a surprising amount of evidence is available. Note that the main anti-inflammatory principle of Tripterygium uiildfordii is a diterpene triepoxide known as triptolide, which posseses potent anti-inflammatory and immunosuppressive properties (103,104). 

Zhao G, Vaszar LT, Qiu D, Shi I, Kao PN. Anti-inflammatory effects of triptolide in human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol 2000 279 L958-L966. 

Feng-Qiao L, Xiu-Zhi L., Xi-Bin L, et al. Triptolide, a Chinese herbal extract, protects dopaminergic neurons from inflammation-mediated damage through inhibition of microglial activation. J Neuroimmunol 2004 148 24-31. 

Tripterygium hypoglaucum (Levi.) Hutch. Shan Hai Ton or Zi Jin Pi (whole plant) Alkaloides, triptolide.33 Anti-infl ammatory, antiswelling. 

Tripterygium wilfordii Hook. f. Lei Gong Teng (Yellow vine) (root) Tripchilorolide, celastrol, triptein, wilfordine, triptophenolide, triptonide, triptolide, tripdiolide, triptolidenol, tripchlorolide, triptolide, tripdioltonide, trihydroxytriptolide, triptolide.33-241-390-431-443 This herb is toxic with adverse effects on gastrointestinal tract. Antifertility effect on male, anti-inflammatory, antitumor, treat cancer, antirheumatoid arthritis, suppressive effects. 

Leuenroth SJ, Okuhara D, Shotwell JD, Markowitz GS, Yu Z, Somlo S, Crews CM (2007) Triptolide is a traditional Chinese medicine-derived inhibitor of polycystic kidney disease. Proc Natl Acad Sci USA 104 4389 1394... 

McCallum C, Kwon S, Leavitt P, Shen D-M, Liu W, Gumett A (2007) Triptolide binds covalently to a 90 kDa nuclear protein. Role of epoxides in binding and activity. Immunobiology 313 549-556... 

Di33 Triptolide Tripterygium wilfordii APO, COX, NFkB, TNFa [96,196-200]... 

ABSTRACT This article reviews the literature published dealing with the synthesis of some bioactive diterpenes. It describes the biological activity and synthesis of only four diterpenes pisiferic acid, camosic acid, triptolide and miltirone. This review excludes the discussions of Taxodione, a bioactive diterpene, because it has already been reviewed [85], The utility of several reagents in the total synthesis of terpenoid compounds has been documented. It can be observed that several routes have been developed for the synthesis of a single diterpene. 

Kupchan et al. [38] first isolated triptolide, a highly oxygenated diterpene from an ethanol ic extract of the Chinese medicinal plant Triptergium... 

Wilfordil Hook F (celastraceae) on the basis of bioassay-directed fractionation. The ethanol extract was concentrated in an ethylacetate layer of an ethylacetate-water participation. The ethylacetate extract was eluted on silica gel with chloroform and 5% methanol in chloroform. The latter fraction was further chromatographed on silica AR-CC-7 with chloroform to yield a triptolide-enriched fraction. This was further chromatographed on silica AR CC-7 to yield triptolide (137) which on crystallization from CH2Cl2-Et20 was obtained as white needles, m.p. 

Berchtold et al. [49] have reported the first total synthesis of racemic triptolide (149) and this is described in Fig. (17). 

The synthesis of triptolide (149) by Berchtold[49], provides many interesting information for organic chemists. An excellent method has been developed for the construction of butenolide ring. The periodate oxidation of o-hydroxymethylphenoles appears to be a convenient method for the stereospecific construction of the C-ring functionality in triptolide and related substances. 

Van Tamelen and coworkers have developed three syntheses of triptolide (149) and these are described in Fig. (18). 

Hydroxymethylation of ketone (155) was followed by protection of the aliphatic hydroxy group (2-methoxypropyl ether) and addition of an a-benzyloxymethylene group at C-4. Acidic workup at the last stage of the reaction sequence produced (156). Its transformation to aldehyde (157) was carried out by successive treatment with methoxypropyl ether, acetic anhydride and pyridine, hydrochloric acid and methanol, and finally chromic acid, pyridine and hydrochloric acid. Dehydration of (157) led to the formation of (158) in 20% yield. Reagents other than the mentioned produced appreciable quantities of the cis A/B isomer. The butenolide (159) was finally synthesized by oxidation and hydrogenolysis. In order to complete the synthesis of triptolide it was necessary to introduce the... 

Fig ( 18 ) A series of reactions are carried out for the conversion of dehydroabietic acid to ketone (155) to hydroxymethyiation, protection of aliphatic hydroxyl group, addition of an -benzyloxymethyl group and acid treatment provides (156) which is con verted to (158). The butenolide function is constructed by successive oxidation and debenzylation to yield (159) which is converted to triptolide (149) by conventional methods. 

The third synthesis of triptolide by van Tamelen [55] features a biomimetic approach to the ring system. This is documented in Fig. (20). 

Isopropyl anisole (171) was converted to bromide (172) by metalation, formylation and bromination. Alkylation with cyclopropyl ketoester produced (173) whose transformation to alcohol (174) was achieved by saponification, decarboxylation and reduction.. Its conversion to homoallylic bromide (175) was accomplished by the method of Julia et al. [56]. Alkylation of ethyl acetoacetate with bromide (175) furnished p-ketoester (176). It was subjected to cyclization with stannic chloride in dichloromethane. The resulting tricyclic alcohol provided the olefinic ester (177) by treatment with mesylchloride and triethylamine. Epoxidation followed by elimination led to the previously reported intermediate (146) whose conversion to triptolide (149) has already been described. 

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