Triptolides derivatives

Dai (6) prepared triptolide derivatives, (V), which were effective in treating or preventing transplantation rejection including graft-versus-host disease. 

The potent antileukemics 79 and 80 contain a characteristic hydrogen-bonded 9,11-epoxy-14P-hydroxy system. As triptonide (81) showed no antileukemic activity in doses up to 0.4 mg/kg, Kupchan et al. [171] hypothesized that this system was necessary for the antileukemic activity of the triptolides. Subsequent testing of the minor variants 14-epitriptolide (82), the main product obtained from the reduction of 81, with a-oriented 14-hydroxyl, and the thiol adducts 83 and 84, obtained by selective alkylation of 79 and 80, respectively (lacking 9,11-epoxide) Fig. (24), revealed that these triptolides derivatives, did not show any... 

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... 

Fig (22) 2-isopropylphenol (183) is converted to allylic alcohol (185). Its bromide derivative reacts with methyl acetoacetate. The resulting compound undergoes radical cyclization yields ketoester (186) whose vinyl triflate on reduction and carbonylation furnishes lactone (187). Diol (188) obtained from (187), is converted to monoepoxide (189) which on further epoxidation produces triptonide (148). Its conversion to triptolide (149) is accomplished by reduction. 

The chemistry of components from the TW plant has been well characterized. The biological activity of these components is under study for the development of clinically useful therapeutic agents. Among the components, triptolide type compounds are being developed for treatment of autoimmune diseases as well as cancer, and other components such as celastrol-type compounds and alkaloids also have prospects for further development. All of these are examples derived from the investigation of Traditional Chinese... 

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