New facile enantio- and diastereo-selective syntheses of (−)-triptonide and (−)-triptolide

Zhang, Hongrui; Li, Haifeng; Xue, Jiangeng; Chen, Rui; Li, Ying; Tang, Yu; Li, Chunxin

doi:10.1039/c3ob42183j

Cited by 18 publications

(11 citation statements)

References 51 publications

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“…Recently,Z hang et al used the Pfau-dAngelo method for the stereoselective alkylation of 5-methoxytetralone 164 with the Nazarov reagent 162 (Scheme 46). [117] Acidic treatment results in the bridged [3.3.1] product 165,b ut alkaline conditions yields the desired enone 166 (with agood 90 % ee) in a1 0:1m ixture along with the tautomeric dienol. Subsequent functionalization yields the known intermediate 167 in the synthesis of both (À)-triptonide and (À)-triptolide.…”

Section: Angewandte Chemiementioning

confidence: 99%

Enantioselective Access to Robinson Annulation Products and Michael Adducts as Precursors

2017

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The Robinson annulation is a reaction that has been useful for numerous syntheses since its discovery in 1935, especially in the field of steroid synthesis. The products are usually obtained after three consecutive steps: the formation of an enolate (or derivative), a conjugate addition, and an aldol reaction. Over the years, several methodological improvements have been made for each individual step or alternative routes have been devised to access the Robinson annulation products. The first part of this Review outlines the most relevant developments towards the formation of monocarbonyl-derived Robinson annulation products (MRA products, MRAPs) and activated monocarbonyl-derived Robinson annulation products (AMRA products, AMRAPs). The following sections are then devoted to the diastereoselective and enantioselective synthesis of these products, while the last section describes the enantiomeric resolution of racemic mixtures.

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Section: Angewandte Chemiementioning

confidence: 99%

Enantioselective Access to Robinson Annulation Products and Michael Adducts as Precursors

2017

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“…The pharmaceutical potential of T. wilfordii diterpenoids has spurred interest in the development of methods for their sustainable and reliable production, particularly given the generally low content of these metabolites, slow growth rate, and the restricted habitat of this species (GBIF, 2016). While cell culture systems and total synthesis have been investigated as sources of T. wilfordii bioactive terpenoids (Kutney et al, 1981;Zhang et al, 2014;Camelio et al, 2015), an attractive alternative yielding access to bioactive terpenoids is the metabolic engineering of microorganisms for heterologous production (Paddon et al, 2013). This approach may ultimately offer economic and environmental benefits, but requires functional knowledge of the biosynthetic pathways of the target molecules.…”

Section: Introductionmentioning

confidence: 99%

The terpene synthase gene family in Tripterygium wilfordii harbors a labdane‐type diterpene synthase among the monoterpene synthase TPS‐b subfamily

et al. 2017

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SUMMARYTripterygium wilfordii (Celastraceae) is a medicinal plant with anti-inflammatory and immunosuppressive properties. Identification of a vast array of unusual sesquiterpenoids, diterpenoids and triterpenoids in T. wilfordii has spurred investigations of their pharmacological properties. The tri-epoxide lactone triptolide was the first of many diterpenoids identified, attracting interest due to the spectrum of bioactivities. To probe the genetic underpinning of diterpenoid diversity, an expansion of the class II diterpene synthase (diTPS) family was recently identified in a leaf transcriptome. Following detection of triptolide and simple diterpene scaffolds in the root, we sequenced and mined the root transcriptome. This allowed identification of the root-specific complement of TPSs and an expansion in the class I diTPS family. Functional characterization of the class II diTPSs established their activities in the formation of four C-20 diphosphate intermediates, precursors of both generalized and specialized metabolism and a novel scaffold for Celastraceae. Functional pairs of the class I and II enzymes resulted in formation of three scaffolds, accounting for some of the terpenoid diversity found in T. wilfordii. The absence of activity-forming abietane-type diterpenes encouraged further testing of TPSs outside the canonical class I diTPS family. TwTPS27, close relative of mono-TPSs, was found to couple with TwTPS9, converting normal-copalyl diphosphate to miltiradiene. The phylogenetic distance to established diTPSs indicates neo-functionalization of TwTPS27 into a diTPS, a function not previously observed in the TPS-b subfamily. This example of evolutionary convergence expands the functionality of TPSs in the TPS-b family and may contribute miltiradiene to the diterpenoids of T. wilfordii.

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“…In 2014, Li and co-workers further reported a formal asymmetric synthesis of triptolide from tetralone 24 (Fig. 2, route B and Scheme 2) [50], featuring a Robinson annulation of Nazarov’s reagent 25 with 5-methoxy-2-tetralone 24 in the presence of enantiomerically pure ( R )-α-phenylethylamine ( 49 ) to generate key tricyclic intermediates 51 and 52 , a Pd(II)-catalyzed carbonylation–lactonization reaction of 9 to construct the butenolide (D-ring), and a Friedel–Crafts isopropylation to install the C-13 isopropyl group. Still, the construction of the C-5 trans junction A-/B-ring was problematic, direct reduction of 51 and 52 with either Pd/BaSO 4 /H 2 or Li/NH 3 / t -BuOH could not give the desired ketoester 54 in satisfactory yield for a target-oriented synthesis.…”

Section: Reviewmentioning

confidence: 99%

A review of the total syntheses of triptolide

Zhang¹,

Xiao²,

Xu³

2019

Beilstein J. Org. Chem.

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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.

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New facile enantio- and diastereo-selective syntheses of (−)-triptonide and (−)-triptolide

Cited by 18 publications

References 51 publications

Enantioselective Access to Robinson Annulation Products and Michael Adducts as Precursors

Enantioselective Access to Robinson Annulation Products and Michael Adducts as Precursors

The terpene synthase gene family in Tripterygium wilfordii harbors a labdane‐type diterpene synthase among the monoterpene synthase TPS‐b subfamily

A review of the total syntheses of triptolide

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