Triptolide synthesis

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. 

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. 

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... 

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

Baneijee and Azocar [57] have developed an alternative synthesis of compound (167) whose transformation to triptolide (149) has already been described. [52] The synthesis of (167) is described in Fig. (21). 

The method described for the synthesis of triptolide is concise and affords good yield in most of the steps. We believe that the experimental procedures are complicated and requires skilled experimentalists. Yang et al [72] have also accomplished an enantioselective total synthesis of (-)-triptolide. 

Tripelennamine as antihistamine, 1, 177 biological activity, 4, 911 toxicity, 4, 912 Tripelennamine, p-bromo-as antihistamine, 2, 520 a-Tripiperideine synthesis, 3, 510 Triprolidine as antihistamine, 1, 177 Triptolide, 7, 192 Tripyrroles synthesis, 4, 415, 416 1,6,6a A4-T riselenapentalenes CNDO calculations, 6, 1052 PE spectra, 6, 1057 Trisilacyclobutanes synthesis, 1, 601... 

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