A review of the total syntheses of triptolide

Abstract

Triptolide is a complex triepoxide diterpene natural product that has attracted considerable interest in the organic chemistry and medicinal chemistry societies due to its intriguing structural features and multiple promising biological activities. In this review, progress in the total syntheses of triptolide are systematically summarized. We hope to gain a better understanding of the field and provide constructive suggestions for future studies of triptolide.

Triptolide: pharmacological spectrum, biosynthesis, chemical synthesis and derivatives

“…Over decades, relatively slow progress has been made toward the goal of total triptolide synthesis, with many of the advancements made attributed the efforts of Berchtold 116 , van Tamelen 117 and Yang 118 . Currently, there are four principal ways to synthesize triptolide: Ⅰ) synthesis from tetralinone, α-abietic acid or α-dehydroabietic acid as starting materials, Ⅱ) synthesis via the Diels-Alder reaction, Ⅲ) synthesis of the core skeleton via a polyene cyclization reaction, and IV) synthesis via metal catalysis 119 .…”

“…Reduction of 12 with NaBH 4 provides pure C-7β alcohol ( 13 ). Finally, triptolide ( 1 , 21%) and 14-epitriptolide (68%) are obtained through an Alder periodate reaction (NaIO 4 , 74%), a sequencing m-CPBA oxygenation and basic hydrogen peroxide oxygenation (H 2 O 2 /OH - ) procedure, and sodium borohydride reduction 119 . In summary, the first total synthesis of racemic triptolide was completed from 5 in 16 steps.…”

“…Many reviews have been focused on triptolide. However, thus far, these reviews have been basically aimed at introducing the research progress of triptolide, such as its anticancer effects 176 , derivative identification 170 and advances in its total chemical synthesis 119 . In this review, triptolide is described in detail from different perspectives such as pharmacological activity and biosynthesis, aiming to provide new ideas for researchers in different disciplines and promote the research progress of triptolide.…”

Recent progress and new perspectives for diterpenoid biosynthesis in medicinal plants

“…Triptolide is a diterpenoid epoxide, which possesses antitumor, immunosuppressive, and anti‐inflammatory properties 13 . The amount of triptolide in Tripterygium plants is extremely low (6–16 ng/g), 103 and its chemical synthesis is cumbersome, with low yield 104 . The production capacity for this compound is therefore insufficient to meet large commercial needs, especially for the industrial production of triptolide and its derivatives.…”

Synthesis of celastrol derivatives as potential non‐nucleoside hepatitis B virus inhibitors

“…Taken together, celastrol should be a promising bioactive natural product for new drug discovery. However, unlike its relative triptolide, lots of total synthesis and structural modifications have conducted in the past two decades (Chen, Zhou, & Li, 2012; Hou, Liu, & Xu, 2019b; Kaloun et al., 2016; Liu et al., 2018; Ning et al., 2018; Patil et al., 2015; Wang et al., 2017; Xu, Chen, Tang, Feng, & Li, 2014; Xu et al., 2017; Xu & Liu, 2019; Xu, Tang, Feng, & Li, 2014a, 2014b; Xu, Tang, Yang, Feng, & Li, 2014; Zhang, Xiao, & Xu, 2019; Zhou, Yang, Ding, Li, & Miao, 2012), and some triptolide derivatives have already entered clinic for the treatment of challenging cancer and/or rheumatoid arthritis (RA) (Carter et al., 2012; Pao et al., 2019; Patil et al., 2012; Wang, Xu, Fu, Li, & Lou, 2012; Zhou et al., 2005). So far, there is only one total synthesis (Camelio, Johnson, & Siegel, 2015) and several chemical modifications of celastrol have been reported (Figueiredo, Salvador, Cortés, & Cascante, 2017a; Jiang et al., 2016; Kyriakou et al., 2018; Li et al., 2015, 2018; Pang, Luo, Liu, Wu, & Wang, 2018; Shan et al., 2017; Tang, Huang, Pan, Zhang, & Lu, 2015; Zhang, Zhang, Piao, & Quan, 2018; Zhu et al., 2017), which are largely focused on its anti‐cancer activity.…”