DIAL-A-TERPENE: NEW CHEMICAL PROTOCOLS ALLOWING FOR THE ITERATIVE SYNTHESIS OF TERPENOIDS

Dial-A-萜烯：允许迭代合成萜类化合物的新化学方案

• 批准号: EP/P030742/1
• 负责人: David Braddock
• 金额: $ 47.2万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FP030742%2F1
• 关键词: DIAL; TERPENE; NEW; CHEMICAL; PROTOCOLS

Terpenoids, comprised of 'head-to-tail' and 'head-to-head' arrangements of five-carbon atom containing (C5) units, are a very large and diverse class of linear and (poly)cyclic natural occuring biomolecules and account for 60% of known natural products (estimated as more than 40 000 distinct chemical structures). Their vital biological functions include lipid membrane modulation, light harvesting and photooxidative protection, electron transport, intercellular signaling as hormones, and interspecies defence amongst others. Their medicinal benefits have been recognised for centuries, initially as traditional herbal remedies from plants, and subsequent development of e.g., steroidal medicines as blockbuster drugs in the 20th century through to the present day (budesonide was the number 1 prescribed drug of 2013). It is well understood that the (poly)cyclic terpenoids all arise from linear (C5)n precursors, and nature constructs the linear precusors by sequential addition of activated C5 phosphate-containing units. These linear terpenoids are important in their own right, being constituents of nearly every living cell, and play vital roles in peptide modification. A very great deal of chemical, biochemical and biological research has been directed towards the understanding of all of the above, and scientific database searches at the time of writing on "terpen*" (as a catch-all for terpene and terpenoid) reveals > 94 000 manuscripts have been published in this area. However, despite the long-term recognition that these linear compounds are essentially C5-repeating units, a general and iterative chemical protocol for their synthesis - using naturally occuring terpenoid building blocks - does not exist. This is in stark contrast to the state of affairs for synthesis of the other main classes of biologically important compounds (peptides, RNA and oligosaccharides) where use of of solid-phase synthesis, iterative coupling protocols and automated methods has revolutionised these research areas. It is thefore the aim of this proposal to develop such chemical protocols for terpenoids.

萜类化合物由含有五个碳原子（C5）单元的“头-尾”和“头-头”排列组成，是一类非常大且多样的线性和（多）环状天然存在的生物分子，占已知天然产物的60%（估计有超过40000种不同的化学结构）。它们的重要生物学功能包括脂质膜调节、光捕获和光氧化保护、电子传递、作为激素的细胞间信号传导和种间防御等。几个世纪以来，它们的药用价值已得到认可，最初是从植物中提取的传统草药，随后发展为例如，甾体类药物作为重磅炸弹药物在20世纪一直到今天（布地奈德是2013年的头号处方药）。众所周知，（多）环萜类化合物都是由线性（C5）n前体产生的，自然界通过依次加入活化的含C5磷酸盐的单元来构建线性前体。这些线性萜类化合物本身就很重要，几乎是每个活细胞的组成部分，并在肽修饰中发挥重要作用。大量的化学、生物化学和生物学研究都是为了理解上述所有内容，在撰写“terpen*”（作为萜烯和萜类化合物的统称）时，科学数据库搜索显示，在这一领域已经发表了> 94 000篇手稿。然而，尽管长期认识到这些线性化合物基本上是C5-重复单元，但使用天然存在的萜类化合物结构单元合成它们的通用和迭代化学方案并不存在。这与其他主要类别的生物重要化合物（肽、RNA和寡糖）的合成状况形成鲜明对比，其中固相合成、迭代偶联方案和自动化方法的使用彻底改变了这些研究领域。因此，本建议的目的是开发此类萜类化合物的化学方案。

项目成果

Relay Cross Metathesis for the Ascent of the Terpenoids

萜类化合物上升的接力交叉复分解

• DOI: 10.26434/chemrxiv.8267837.v1
• 发表时间: 2019
• 作者: Bahou K

A Relay Strategy Actuates Pre-Existing Trisubstituted Olefins in Monoterpenoids to Form New Trisubstituted Olefins by Cross Metathesis

中继策略驱动单萜类化合物中预先存在的三取代烯烃通过交叉复分解形成新的三取代烯烃

• DOI: 10.26434/chemrxiv.8267837
• 发表时间: 2019
• 作者: He T

Relay Cross Metathesis for the Iterative Construction of Terpenoids and Synthesis of a Diterpene-Benzoate Macrolide of Biogenetic Relevance to the Bromophycolides.

用于迭代构建萜类化合物和合成与溴藻内酯生物遗传相关的二萜-苯甲酸酯大环内酯的中继交叉复分解。

• DOI: 10.1021/acs.orglett.0c00935
• 发表时间: 2020
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Bahou KA

(±)-Polysiphenol and Other Analogues via Symmetrical Intermolecular Dimerizations: A Synthetic, Spectroscopic, Structural, and Computational Study.

(±)-聚苯酚和其他类似物通过对称分子间二聚化：合成、光谱、结构和计算研究。

• DOI: 10.1021/acs.jnatprod.2c00749
• 发表时间: 2022-11-25
• 期刊: JOURNAL OF NATURAL PRODUCTS
• 影响因子: 5.1
• 作者: Braddock, D. Christopher;Duran-Corbera, Anna;Nilforoushan, Masih;Yang, Ziye;He, Tianyou;Santhakumar, Gajan;Bahou, Karim A.;Rzepa, Henry S.;Woscholski, Rudiger;White, Andrew J. P.
• 通讯作者: White, Andrew J. P.

Relay Cross Metathesis for the Iterative Ascent of the Terpenoids

萜类化合物迭代上升的接力交叉复分解

• DOI: 10.26434/chemrxiv.8267837.v2
• 发表时间: 2019
• 作者: Bahou K