38647-11-9Relevant articles and documents
Triptolide derivatives as potential multifunctional anti-Alzheimer agents: Synthesis and structure–activity relationship studies
Ning, Chengqing,Mo, Liumei,Chen, Xuwei,Tu, Wentong,Wu, Jun,Hou, Shengtao,Xu, Jing
, p. 689 - 693 (2018)
Owning to the promising neuroprotective profile and the ability to cross the blood–brain barrier, triptolide has attracted extensive attention. Although its limited solubility and toxicity have greatly hindered clinical translation, triptolide has nonetheless emerged as a promising candidate for structure–activity relationship studies for Alzheimer's disease. In the present study, a series of triptolide analogs were designed and synthesized, and their neuroprotective and anti-neuroinflammatory effects were then tested using a cell culture model. Among the triptolide derivatives tested, a memantine conjugate, compound 8, showed a remarkable neuroprotective effect against Aβ1–42 toxicity in primary cortical neuron cultures as well as an inhibitory effect against LPS-induced TNF-α production in BV2 cells at a subnanomolar concentration. Our findings provide insight into the different pharmacophores that are responsible for the multifunctional effects of triptolide in the central nervous system. Our study should help in the development of triptolide-based multifunctional anti-Alzheimer drugs.
Method for asymmetrically synthesizing Triptonide and Triptolide
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Paragraph 0140-0150, (2021/08/25)
The invention discloses a method for asymmetrically synthesizing triptonide and triptolide, the method comprises the following steps: starting from (-)-Taniguchi lactone, developing a framework structure of the triptolide through alkylation reaction, transition metal catalytic hydrogen atom transfer reaction and aldol type ring closing reaction, further completing total synthesis of the triptonide through oxidation reaction, and converting the triptonide into the triptolide through a known reduction reaction. The reaction operation in the synthesis is simple, the method can be widely popularized and used, and a foundation is laid for further structure-function relationship research and structure optimization of the triptolide and the triptolide.
Design, synthesis and structure-activity relationships studies on the d ring of the natural product triptolide
Xu, Hongtao,Tang, Huanyu,Feng, Huijin,Li, Yuanchao
supporting information, p. 290 - 295 (2014/04/03)
Triptolide is a diterpene triepoxide natural product isolated from Tripterygium wilfordii Hook F, a traditional Chinese medicinal herb. Triptolide has previously been shown to possess antitumor, anti-inflammatory, immunosuppressive, and antifertility activities. Earlier reports suggested that the five-membered unsaturated lactone ring (D ring) is essential for potent cytotoxicity, however, to the best of our knowledge, systematic structure- activity relationship studies have not yet been reported. Here, four types of D ring-modified triptolide analogues were designed, synthesized and evaluated against human ovarian (SKOV-3) and prostate (PC-3) carcinoma cell lines. The results suggest that the D ring is essential to potency, however it can be modified, for example to C18 hydrogen bond acceptor and/or donor furan ring analogues, without complete loss of cytotoxic activity. Interestingly, evaluation of the key series of C19 analogues showed that this site is exquisitely sensitive to polarity. Together, these results will guide further optimization of this natural product lead compound for the development of potent and potentially clinically useful triptolide analogues.
Efficient syntheis of the key intermediate triptophenolide methyl ether for the synthesis of(-)-triptolide
Zhou, Bing,Li, Xiaomei,Feng, Huijin,Li, Yuanchao
scheme or table, p. 5396 - 5401 (2010/08/19)
An efficient synthesis of triptophenolide methyl ether 4 from the readily available abietic acid 3 in nine steps is described and successfully applied to the synthesis of (-)-triptolide 1.The route is of characteristic of low cost, high yield and easy operation.In addition, every reaction in this route has been successfully scaled-up to a 100 g substrate level without loss of yield.
Semisynthesis of C-ring modified triptolide analogues and their cytotoxic activities
Aoyagi, Yutaka,Hitotsuyanagi, Yukio,Hasuda, Tomoyo,Fukaya, Haruhiko,Takeya, Koichi,Aiyama, Ritsuo,Matsuzaki, Takeshi,Hashimoto, Shusuke
, p. 1947 - 1949 (2007/10/03)
Several C-ring modified analogues of a potent antileukemic diterpene, triptolide (1), were synthesized and their structure-activity relationships were studied.
Enantioselective Total Synthesis of (-)-Triptolide, (-)-Triptonide, (+)-Triptophenolide, and (+)-Triptoquinonide
Yang, Dan,Ye, Xiang-Yang,Xu, Ming
, p. 2208 - 2217 (2007/10/03)
The first enantioselective total synthesis of (-)-triptolide (1), (-)-triptonide (2), (+)-triptophenolide (3), and (+)-triptoquinonide (4) was completed. The key step involves lanthanide triflate-catalyzed oxidative radical cyclization of (+)-8-phenylmenthyl ester 30 mediated by Mn(OAc)9, providing intermediate 31 with good chemical yield (77%) and excellent diastereoselectivity (dr 38:1). (+)-Triptophenolide methyl ether (5) was then prepared in >99% enantiomeric excess (>99% ee), and readily converted to natural products 1-4. In addition, transition state models were proposed to explain the opposite chiral induction observed in the oxidative radical cyclization reactions of chiral β-keto esters 17 (without an α-substituent) and 17a (with an α-chloro substituent).
