10,11-oxidosqualene | 365456-24-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 10,11-oxidosqualene
• 英文别名: 2-[(3E)-4,8-dimethylnona-3,7-dienyl]-2-methyl-3-[(3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienyl]oxirane
• CAS: 365456-24-2
• 化学式: C₃₀H₅₀O
• 分子量: 426.726
• InChiKey: OZBVWSJPTAXJQA-JSFDVHLOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.4
• 重原子数：
  31
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  10,11-oxidosqualene 在 N-溴代丁二酰亚胺(NBS) 、 sodium hydride 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 生成 2,3:10,11-dioxidosqualene
  参考文献：
  名称：

  Dioxidosqualenes: characterization and activity as inhibitors of 2,3-oxidosqualene-lanosterol cyclase

  摘要：

  The preparation and characterization of dioxidosqualenes 4-10 is reported. Treatment of the appropriate epoxysqualene 1, 2, or 3 with NBS followed by chromatographic purification afforded the corresponding epoxybromohydrins 11-14 as diastereomeric mixtures, with the exception of compound 11, which could be separated into the respective racemates 11a and 11b. Further dehydrobromination with NaH in THF led to the respective dioxidosqualenes 4-8 in good conversion yields. Dioxides 9 and 10 were isolated from the crude reaction mixture of the treatment of epoxide 2 with dimethyldioxirane. Characterization of compounds 4-10 was carried out by combining IH and C-13 NMR spectral means with positive GC-MS-CI analysis. The GC-MS-CI analysis included the identification of the carbonyl compounds resulting from the cleavage of dioxido derivatives 4-10 with periodic acid. Finally, data on the activity of dioxidosqualenes as oxidosqualene-lanosterol cyclase (OSLC) inhibitors in rat liver microsomes are also presented. In this respect, 2,3:18,19-dioxidosqualene (7) was found to be the best inhibitor within the compounds assayed (IC50 = 0.11 muM), although dioxides 4, 5, and 9 also exhibited a potent inhibitory activity (IC50 = 21.3, 13.0, and 9.3 muM, respectively). The fact that these compounds could be potentially generated in an organism constitutes a remarkable difference relative to other OSLC inhibitors described to date.

  DOI：

  10.1021/jo00067a036
• 作为产物：
  描述：

  角鲨烯 在 magnesium monoperoxyphthalate hexahydrate 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 10,11-oxidosqualene 、 6,7-oxidosqualene
  参考文献：
  名称：

  26-和29-羟基-2,3-氧化角鲨烯的酶环化反应生成19-和21-羟基羊毛甾醇

  摘要：

  使用贝克酵母悬浮液将29-羟基-2,3-氧化角鲨烯以接近定量的产率（基于（3 S）对映异构体的利用）转化为21-羟基羊毛甾醇。类似地，26-羟基-2,3-氧化角鲨烯被有效地环化为19-羟基羊毛甾醇。

  DOI：

  10.1016/0040-4039(91)80421-2

文献信息

• Squalene-Hopene Cyclase: On the Polycyclization Reactions of Squalene Analogues Bearing Ethyl Groups at Positions C-6, C-10, C-15, and C-19
  作者：Kazunari Takahashi、Yusuke Sasaki、Tsutomu Hoshino

  DOI：10.1002/ejoc.201800010

  日期：2018.3.29

  The cyclization of Et‐substituted squalenes (SQs) at C‐6, C‐10, C‐15, and C‐19 by squalene‐hopene cyclase has been studied. No reaction occurred with 6‐EtSQ, and mono‐ and bicyclic products were obtained with 10‐ and 15‐EtSQ. In contrast, 19‐EtSQ was converted into mono‐, bi‐, tetra‐, and pentacyclic products. The products give an insight into the binding in the recognition sites in the cyclase.

  研究了角鲨烯-环戊烯环化酶在C-6，C-10，C-15和C-19上对Et取代的角鲨烯（SQs）的环化作用。6-EtSQ没有反应发生，而10-和15-EtSQ获得了单环和双环产物。相反，19-EtSQ被转化为单，双，四和五环产物。该产品可深入了解环化酶中识别位点的结合。
• Squalene–hopene cyclase: insight into the role of the methyl group on the squalene backbone upon the polycyclization cascade. Enzymatic cyclization products of squalene analogs lacking a 26-methyl group and possessing a methyl group at C(7) or C(11)
  作者：Shin-ichi Nakano、Shumi Ohashi、Tsutomu Hoshino

  DOI：10.1039/b404287e

  日期：——

  To provide deep insight into the polycyclization reaction of squalene, some analogs were synthesized and incubated with the cell-free homogenates of the recombinant Escherichia coli encoding the wild-type squalene cyclase. The presence of C(6)–Me leads to an efficient polycyclization cascade. Substitution of the C(14)–H and the C(18)–H with a methyl group halted the polycylization reaction at the tricyclic ring stage having a 6/6/6-fused ring system and the tetracycle with a 6/6/6/6-fused ring, respectively, both of which were produced according to a Markovnikov closure. Replacement of the C(7)–H and the C(11)–H with a methyl group led to no cyclization. These results, in conjunction with our previous reports, indicated that the methyl positions are important for bringing to completion of the normal polycylization reaction and further demonstrated that the precise steric bulk size at the methyl positions of squalene is critical to the correct folding and the strong binding of the substrate to the squalene cyclase.

  为了深入了解鲨烯的多环化反应，合成了一些类似物，并与编码野生型鲨烯环化酶的重组大肠杆菌的无细胞匀浆一起孵育。C(6)–Me的存在导致了一个高效的多环化级联反应。用甲基取代C(14)–H和C(18)–H分别使多环化反应在具有6/6/6融合环系统的三环阶段和具有6/6/6/6融合环的四环阶段停止，这两者都是按照马克尼科夫闭合反应生成的。用甲基替代C(7)–H和C(11)–H则未导致环化。结合我们之前的报告，这些结果表明甲基位置对正常多环化反应的完成至关重要，并进一步证明鲨烯中甲基位置的精确立体体积对于底物与鲨烯环化酶的正确折叠和强结合至关重要。
• New Cyclization Mechanism for Squalene: a Ring-expansion Step for the Five-membered C-ring Intermediate in Hopene Biosynthesis
  作者：Tsutomu HOSHINO、Masanori KOUDA、Takamasa ABE、Shumi OHASHI

  DOI：10.1271/bbb.63.2038

  日期：1999.1

  Three triterpenes having the 6/6/5-fused tri- and 6/6/6/5-fused tetracyclic skeletons were isolated from an incubation mixture of the mutated F601A enzyme, these products being in accordance with a Markovnikov closure. Successful trapping of the tricyclic cationic intermediate by using the squalene analog having a highly nucleophilic hydroxyl group leads us to propose that the ring expansion process

  从突变的F601A酶的温育混合物中分离出具有6/6 / 5-融合的三环和6/6/6 / 5-融合的四环骨架的三个三萜，这些产物与Markovnikov封闭法一致。通过使用具有高度亲核羟基的角鲨烯类似物成功捕获三环阳离子中间体，使我们提出5元C环的扩环过程涉及角鲨烯环化级联反应。
• Two Concise Enantioselective Total Syntheses of (−)-Glabrescol Implicate Alternative Biosynthetic Pathways Starting from Squalene
  作者：Peng Yang、Pei-Fang Li、Jin Qu、Liang-Fu Tang

  DOI：10.1021/ol3016836

  日期：2012.8.3

  The C2-symmetric (−)-glabrescol was synthesized in two steps from (10S,11R)-dihydroxy-10,11-dihydrosqualene or squalene with 50% or 10% overall yields, respectively. These highly efficient and biomimetic syntheses employed a base-promoted middle-to-terminal double epoxide-opening cascade, which constructs the five tetrahydrofuran rings in glabrescol in one operation.

  所述Ç 2 -对称（ - ） - glabrescol在从两个步骤（10合成小号，11 - [R ）-二羟基-10,11- dihydrosqualene或角鲨烯与分别为50％或10％的总产率，。这些高效且仿生的合成过程采用了碱促进的中端至双端双环氧化物开放级联反应，该反应可在一次操作中在甘草糖醇中构建五个四氢呋喃环。
• Investigation of the Effects of Squalene and Squalene Epoxides on the Homeostasis of Coenzyme Q10 in Rats by UPLC‐Orbitrap MS
  作者：Wenjing Yu、Kaiju Sun、Liying Zhang、Xilin Wan、Changbao Chen、Rui Su、Yifei Liu、Hongfeng Wang、Hongmei Yang

  DOI：10.1002/cbdv.202000243

  日期：2020.8

  to its potential cancer-preventive function. However, the mechanism has not yet been investigated in detail. Therefore, the aim of this study is to see if the plasma coenzyme Q 10 (CoQ 10 ) level will be altered by gavage of squalene and oxidosqualenes to rats. In the present work, a sensitive and simple high-performance analytical method based on ultra-high-performance liquid chromatography coupled

  由于其潜在的癌症预防功能，角鲨烯长期以来一直被用作膳食补充剂。然而，尚未对其机制进行详细研究。因此，本研究的目的是观察血浆辅酶 Q 10 (CoQ 10 ) 水平是否会因给大鼠灌胃角鲨烯和氧化角鲨烯而改变。在目前的工作中，开发了一种基于超高效液相色谱与 Orbitrap 质谱联用 (UPLC-Orbitrap-MS) 的灵敏且简单的高效分析方法，用于定量大鼠血浆中的 CoQ 10。辅酶Q 9 (CoQ 9 )用作内标。CoQ 10 是在乙腈介导的血浆蛋白沉淀后使用 UPLC-Orbitrap-MS 在负离子模式下测定的。每天一次给大鼠灌胃角鲨烯和两种角鲨烯环氧化物几天后，它们血浆中 CoQ 10 的水平升高，但高剂量 (286 mg/kg) 和低剂量 (143 mg/kg) 之间没有显着差异。公斤）组。连续 5 天每天一次的角鲨烯和连续 3 天每天一次的氧化角鲨烯的胃内给药对于达到 CoQ