葫芦二烯醇 | 35012-08-9

• 物质功能分类: 化学试剂 - 有机试剂 - 烯烃（环状与无环状）
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 中文名称: 葫芦二烯醇
• 英文名称: cucurbitadienol
• 英文别名: 10α-cucurbitadienol；3β-hydroxy-cucurbita-5,24-diene；(3S,8R,9R,10S,13R,14S,17R)-4,4,9,13,14-pentamethyl-17-[(2R)-6-methylhept-5-en-2-yl]-2,3,7,8,10,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-ol
• CAS: 35012-08-9
• 化学式: C₃₀H₅₀O
• 分子量: 426.726
• InChiKey: WSPRAEIJBDUDRX-FBJXRMALSA-N

物化性质

• 沸点：
  499.4±14.0 °C(Predicted)
• 密度：
  0.98±0.1 g/cm3(Predicted)
• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

制备方法与用途

葫芦二烯醇（10α-葫芦二烯醇）是一种天然产物，能在瓜蒌种子中找到。葫芦二烯醇具有抗炎作用。

反应信息

• 作为反应物：
  描述：

  葫芦二烯醇 在 platinum(IV) oxide 氢气 作用下， 以 乙醇 为溶剂， 生成 10α-Cucurbit-5-en-3β-ol
  参考文献：
  名称：

  7-OX0-10α-Cucurbitadienol from the seeds of Trichosanthes kirilowii and its anti-inflammatory effect

  摘要：

  The structure of a new triterpene isolated from the seeds of Trichosanthes kirilowii was determined to be 7-oxo-10 alpha-cucurbita-5,24-dien-3 beta-ol (7-oxo-10 alpha-cucurbitadienol) by spectral and chemical methods. 7-0xo-10 alpha-cucurbitadienol, and its acetyl and 24-dihydro derivatives showed marked inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear inflammation in mice. The 50% inhibitory dose of these compounds for TPA-induced inflammation (1 mu g ear(-1)) was 0.4-0.7 mg ear(-1).

  DOI：

  10.1016/s0031-9422(00)97029-8
• 作为产物：
  描述：

  2,3环氧角鲨烯 在 Cucurbita pepo cucurbitadienol synthase L₄₈₈P mutant 作用下， 生成 葫芦二烯醇
  参考文献：
  名称：

  在三萜生物合成过程中通过氧化角鲨烯环化酶控制1,2-重排过程†

  摘要：

  氧化角鲨烯环化酶（OSC）通过一系列阳离子-π环化和1,2-重排过程催化无环底物环化为各种多环三萜。尚未确定OSC控制中间碳阳离子的命运以生成每种特定的三萜产物的机制。植物中普遍存在的固醇前体，环戊烯醇和葫芦科植物特定葫芦二烯醇的形成仅因甲基和氢化物的1,2-重排程度不同而异。在本研究中，我们确定了环戊烯醇合酶和葫芦二烯醇合酶中的关键残基，这些残基主要负责在这两种化合物之间切换产物特异性。环戊烯醇合酶中酪氨酸118突变为亮氨酸导致产生瓜氨酸二烯醇作为主要产物，葫芦二烯醇合酶中相应的亮氨酸125残基突变为酪氨酸导致生成了厚朴酚。我们对“转换”残基的发现将为OSC的合理工程设计生产所需的三萜烯开辟未来的可能性。

  DOI：

  10.1039/c5ob00714c

文献信息

• Functional Characterization of Cucurbitadienol Synthase and Triterpene Glycosyltransferase Involved in Biosynthesis of Mogrosides from Siraitia grosvenorii
  作者：Longhai Dai、Can Liu、Yueming Zhu、Jiangsheng Zhang、Yan Men、Yan Zeng、Yuanxia Sun

  DOI：10.1093/pcp/pcv043

  日期：2015.6

  Mogrosides, the major bioactive components isolated from the fruits of Siraitia grosvenorii, are a family of cucurbitane-type tetracyclic triterpenoid saponins that are used worldwide as high-potency sweeteners and possess a variety of notable pharmacological activities. Mogrosides are synthesized from 2,3-oxidosqualene via a series of reactions catalyzed by cucurbitadienol synthase (CbQ), Cyt P450s (P450s) and UDP glycosyltransferases (UGTs) in vivo. However, the relevant genes have not been characterized to date. In this study, we report successful identification of SgCbQ and UGT74AC1, which were previously predicted via RNA-sequencing (RNA-seq) and digital gene expression (DGE) profile analysis of the fruits of S. grosvenorii. SgCbQ was functionally characterized by expression in the lanosterol synthase-deficient yeast strain GIL77 and was found to accumulate cucurbitadienol as the sole product. UGT74AC1 was heterologously expressed in Escherichia coli as a His-tag protein and it showed specificity for mogrol by transfer of a glucose moiety to the C-3 hydroxyl to form mogroside IE by in vitro enzymatic activity assays. This study reports the identification of CbQ and glycosyltransferase from S. grosvenorii for the first time. The results also suggest that RNA-seq, combined with DGE profile analysis, is a promising approach for discovery of candidate genes involved in biosynthesis of triterpene saponins.

  莫格罗苷是从西瑞亚果中分离出的主要生物活性成分，属于葫芦烷型四环三萜皂苷，在全世界范围内被用作高效甜味剂，并具有多种显著的药理活性。莫格罗苷由2,3-氧代甾烷通过一系列反应合成，这些反应由葫芦烷二烯醇合成酶（CbQ）、细胞色素P450酶（P450s）和UDP糖基转移酶（UGTs）在体内催化。然而，相关基因迄今尚未得到鉴定。在这项研究中，我们成功鉴定了SgCbQ和UGT74AC1，此前通过RNA测序（RNA-seq）和西瑞亚果的数字基因表达谱（DGE）分析预测了这两个基因。SgCbQ的功能特征是通过在缺乏羊毛甾醇合酶的酵母菌株GIL77中的表达来鉴定，发现其作为唯一产物积累葫芦烷二烯醇。UGT74AC1作为His标签蛋白在大肠杆菌中异源表达，并通过将葡萄糖部分转移到C-3羟基上形成莫格罗苷IE，在体外酶促活性测定中显示出对莫格罗苷的特异性。这项研究首次鉴定了西瑞亚果中的CbQ和糖基转移酶。研究
• Oxidation of Cucurbitadienol Catalyzed by CYP87D18 in the Biosynthesis of Mogrosides from<i>Siraitia grosvenorii</i>
  作者：Jiangsheng Zhang、Longhai Dai、Jiangang Yang、Can Liu、Yan Men、Yan Zeng、Yi Cai、Yueming Zhu、Yuanxia Sun

  DOI：10.1093/pcp/pcw038

  日期：2016.5

  Mogrosides, the principally bioactive compounds extracted from the fruits of Siraitia grosvenorii, are a group of glycosylated cucurbitane-type tetracyclic triterpenoid saponins that exhibit a wide range of notable biological activities and are commercially available worldwide as natural sweeteners. The biosynthesis of mogrosides involves initial cyclization of 2,3-oxidosqualene to the triterpenoid skeleton of cucurbitadienol, followed by a series of oxidation reactions catalyzed by Cyt P450s (P450s) and then glycosylation reactions catalyzed by UDP glycosyltransferases (UGTs). We previously reported the identification of a cucurbitadienol synthase (SgCbQ) and a mogrol C-3 hydroxyl glycosyltransferase (UGT74AC1). However, molecular characterization of further transformation of cucurbitadienol to mogrol by P450s remains unavailable. In this study, we report the successful identification of a multifunctional P450 (CYP87D18) as being involved in C-11 oxidation of cucurbitadienol. In vitro enzymatic activity assays showed that CYP87D18 catalyzed the oxidation of cucurbitadienol at C-11 to produce 11-oxo cucurbitadienol and 11-hydroxy cucurbitadienol. Furthermore, 11-oxo-24,25-epoxy cucurbitadienol as well as 11-oxo cucurbitadienol and 11-hydroxy cucurbitadienol were produced when CYP87D18 was co-expressed with SgCbQ in genetic yeast, and their structures were confirmed by liquid chromatography–solid-phase extraction–nuclear magnetic resonance–mass spectrometry coupling (LC-SPE-NMR-MS). Taken together, these results suggest a role for CYP87D18 as a multifunctional cucurbitadienol oxidase in the mogrosides pathway.

  ides生物合成中的作用。
• Promiscuous Oxidosqualene Cyclases from <i>Neoalsomitra integrifoliola</i> Catalyzing the Formation of Tetracyclic, Pentacyclic, and Heterocyclic Triterpenes
  作者：Xiao-Bo Li、Chun-Li Huang、Ying Zhang、Jing-Yang Ding、Gui-Sheng Xiang、Guang-Hui Zhang、Sheng-Chao Yang、Bing Hao

  DOI：10.1021/acs.orglett.4c00730

  日期：2024.4.19

  cyclases (NiOSC1–NiOSC6) from Neoalsomitra integrifoliola were characterized for the biosynthesis of diverse triterpene scaffolds, including tetracyclic and pentacyclic triterpenes from the 2,3-oxidosqualene (1) and oxacyclic triterpenes from the 2,3:22,23-dioxidosqualene (2). NiOSC1 showed high efficiency in the production of naturally rare (20R)-epimers of oxacyclic triterpenes. Mutagenesis results revealed

  来自Neoalsomitra integrifoliola的六种氧化角鲨烯环化酶 ( Ni OSC1– Ni OSC6) 被表征用于生物合成多种三萜支架，包括来自 2,3-氧化角鲨烯 ( 1 ) 的四环和五环三萜和来自 2,3:22,23 的氧杂环三萜-二氧化角鲨烯( 2 )。 Ni OSC1 在生产天然稀有的氧杂环三萜 (20 R )-差向异构体方面表现出高效率。诱变结果表明，与野生型相比， Ni OSC1-F731G 突变体显着增加了 (20 R )-差向异构体的产量。同源建模和分子对接阐明了环氧化物加成步骤中 (20 R )-构型的起源。
• Acid-catalyzed isomerization of cycloartane triterpene alcohols. The formation of cucurbitane- and lanostane-type isomers
  作者：Naoto Shimizu、Toshihiro Itoh、Masao Saito、Taro Matsumoto

  DOI：10.1021/jo00178a030

  日期：1984.2
• Control of the 1,2-rearrangement process by oxidosqualene cyclases during triterpene biosynthesis
  作者：Shohei Takase、Yusuke Saga、Nozomi Kurihara、Shingo Naraki、Kenta Kuze、Genki Nakata、Takeshi Araki、Tetsuo Kushiro

  DOI：10.1039/c5ob00714c

  日期：——

  residues in cycloartenol synthase and cucurbitadienol synthase that were primarily responsible for switching product specificities between the two compounds. The mutation of tyrosine 118 to leucine in cycloartenol synthase resulted in the production of cucurbitadienol as a major product, while the mutation of the corresponding residue leucine 125 to tyrosine in cucurbitadienol synthase resulted in

  氧化角鲨烯环化酶（OSC）通过一系列阳离子-π环化和1,2-重排过程催化无环底物环化为各种多环三萜。尚未确定OSC控制中间碳阳离子的命运以生成每种特定的三萜产物的机制。植物中普遍存在的固醇前体，环戊烯醇和葫芦科植物特定葫芦二烯醇的形成仅因甲基和氢化物的1,2-重排程度不同而异。在本研究中，我们确定了环戊烯醇合酶和葫芦二烯醇合酶中的关键残基，这些残基主要负责在这两种化合物之间切换产物特异性。环戊烯醇合酶中酪氨酸118突变为亮氨酸导致产生瓜氨酸二烯醇作为主要产物，葫芦二烯醇合酶中相应的亮氨酸125残基突变为酪氨酸导致生成了厚朴酚。我们对“转换”残基的发现将为OSC的合理工程设计生产所需的三萜烯开辟未来的可能性。