(3S)-2,3-dihydroxy-2,3-dihydrosqualene | 63976-64-7

• 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: (3S)-2,3-dihydroxy-2,3-dihydrosqualene
• 英文别名: (S)-2,3-dihydroxy-2,3-dihydrosqualene；2,3(S)-Dihydroxy-6,7-dihydrosqualene；(3S,all-E)-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18,22-pentaene-2,3-diol；(-)-squalene 2,3-glycol；(-)-2,3-Dihydrosqualen-2,3-diol；(3S,6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-6,10,14,18,22-pentaene-2,3-diol
• CAS: 63976-64-7
• 化学式: C₃₀H₅₂O₂
• 分子量: 444.742
• InChiKey: GRPNWQFOKYUABH-RSKUXYSASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.3
• 重原子数：
  32
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3S)-2,3-dihydroxy-2,3-dihydrosqualene 在 Triton X-100 、 氢氧化钾 作用下， 以 甲醇 为溶剂， 反应 12.5h， 以33%的产率得到(3R,6E,10E)-13-[(1S,4aS,8aS)-5,5,8a-trimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-2,6,10-trimethyltrideca-6,10-diene-2,3-diol
  参考文献：
  名称：

  Production of epoxydammaranes by the enzymatic reactions of (3R)- and (3S)-2,3-squalene diols and those of 2,3:22,23-dioxidosqualenes with recombinant squalene cyclase and the mechanistic insight into the polycyclization reactions

  摘要：

  通过角鲨烯环化酶对(3R)-和(3S)-2,3-鲨烯二醇进行酶环化，可得到双环化合物和环氧达玛烷，两者的比例约为 3:2。环氧达玛烷支架的形成表明，6/6/6/5-融合的四环阳离子作为中间体参与了多环化反应。2,3:22,23-二氧二十二烷也能产生环氧达玛烷骨架，即 3α- 或 3β- 羟基环氧达玛烷，但产生的双环化合物的数量明显低于角鲨烯二醇，这表明二醇较大的立体体积对多环化途径的影响要大于较小的过氧化物体积。除一种产物外，所有环氧达玛烷都具有 17R、20R 立体化学结构，这表明这些类似物在反应腔中折叠成全椅构象。对所观察到的立体化学特异性的机理认识表明，有组织的全椅构象受到角鲨烯环化酶的严格限制，因此反应腔内不允许自由构象变化；羟基或环氧化物朝中间阳离子方向的微小旋转可产生高产率的酶促产物，而较大的旋转则导致产物的低产率。生成的环氧达玛烷的立体化学结构与天然来源的环氧达玛烷相反，因此这里描述的几乎所有酶产物都是新的。

  DOI：

  10.1039/b615897h
• 作为产物：
  描述：

  三十碳六烯-2,3-二醇 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 (3S)-2,3-dihydroxy-2,3-dihydrosqualene
  参考文献：
  名称：

  2,3-和内部赤型-角鲨烯二醇的丙烯酸的衍生化。分离和绝对配置确定

  摘要：

  我们研究了一种新的方法，用于拆分和制备角鲨烯二醇的对映异构体，作为对映异构体的绝对构型，该对映体是化学合成不同的角鲨烯氧化物（SOs）的中间前体。（3 R）-和（3 S）-2,3-SO，（6 R，7 R）-和（6 S，7 S）-6,7-SO和（10 R，11 R）-和（10 S，11 S）-10,11-SO。相应的外消旋角鲨烯二醇中间体与（S）-（+）-甲氧基苯基乙酸（（S）-（+）-MPA），（S）-（+）-9-甲氧基甲氧基乙酸（（S）-（+）-9-AMA）和（S）-（+）-乙酰氧基苯基乙酸（（S）-（+）-APA）提供了非对映体酯，其可以通过硅胶快速柱色谱法容易地分离。另外，有利的是根据描述的这些衍生手性试剂的模型，由1 H NMR数据推断出这些衍生的二醇的这些非对映异构体的绝对构型。为了证明不同的立体异构体的绝对构型的分配，（小号） - （+） - AMA显示较大的Δ δ由1 H NMR，然而，（小号）

  DOI：

  10.1016/j.tet.2004.09.059

文献信息

• Asymmetric dihydroxylation of squalene
  作者：Gerard A. Crispino、K.Barry Sharpless

  DOI：10.1016/s0040-4039(00)74236-5

  日期：1992.7

  The asymmetric dihydroxylation of squalene was studied using the new ligand (DHQD)2-PHAL. Moderate positional selectivity for the 2,3-olefin was observed with high % ee.

  使用新的配体（DHQD）2 -PHAL研究了角鲨烯的不对称二羟基化。在高ee百分比下，观察到对2,3-烯烃的中等位置选择性。
• Highly Effective Transition Structure Designed Catalyst for the Enantio<i>- </i>and Position<i>-</i>Selective Dihydroxylation of Polyisoprenoids
  作者：E. J. Corey、Junhu Zhang

  DOI：10.1021/ol016577i

  日期：2001.10.1

  GRAPHICSThe chiral monocinchona derivative shown, synthesized in one step from two efficiently prepared chiral building blocks, was designed under mechanistic guidance as a catalyst for the enantio- and position-selective dihydroxylation of the terminal isopropylidene group of polylsoprenoids. Its efficacy as a synthetic reagent for this purpose was demonstrated for several different substrates.
• Boar; Damps, Journal of the Chemical Society. Perkin transactions I, 1977, # 6, p. 709 - 712
  作者：Boar、Damps

  DOI：——

  日期：——
• Internal Oxidosqualenes: Determination of Absolute Configuration and Activity as Inhibitors of Purified Pig Liver Squalene Epoxidase
  作者：Jose-Luis Abad、Josefina Casas、Francisco Sanchez-Baeza、Angel Messeguer

  DOI：10.1021/jo00117a014

  日期：1995.6

  The preparation and characterization of oxidosqualenes 3-(6R,7R), 3-(6S,7S), 4-(10R,11R), and 4-(10S,11S) is reported. Squalenediol 6 was converted into the corresponding mixture of(R)-Mosher esters 8 and 9, which were separated by semipreparative HPLC. Esters 8 and 9 were reduced to the chiral diols 6-(6R,7S) and 6-(6S,7R), respectively, which were finally converted into the corresponding epoxides 3-(6R,7R) and 3-(6S,7S). A similar procedure was used for the preparation of chiral epoxy derivatives 4-(10R,11R) and 4-(10S,11S) from esters 10 and 11, respectively. The determination of the absolute configuration of these epoxides was carried out by using the method reported by Ohtani et al. (J. Am. Chem. Sec. 1991, 113, 4092), which was adapted to the case of racemic mixtures from synthetic origin. For this purpose, the (R)-Mosher esters derived from the enantiomers of squalenediols 6 or 7 were used. The validity of this approach was confirmed by the absolute configuration found for the three squalenediols 6-(6R,7R), 6-(6S,7S), 7-(10R,11R), and 7-(10S,11S) formed in the Sharpless asymmetric dihydroxylation of squalene (Crispino, G. A.; Sharpless, K. B. Tetrahedron Lett. 1992, 33, 4273). Results on the inhibitory activity of oxidosqualenes 3-(6R,7R), 3-(6S,7S), 4-(10R,11R), and 4-(10S,11S) using purified squalene epoxidase (SE) fi om pig liver showed that epoxide 3-(6S,7S) was the best inhibitor within the compounds assayed (IC50 = 6.7 mu M), although oxidosqualene 4-(10R,11R) also exhibited a moderate inhibitory activity (IC50 = 25 mu M). The inhibition elicited by the epoxy derivative 3-(6S,7S) was competitive with respect to squalene (K-i = 2.7 mu M). This activity is comparable to that reported for the most potent competitive SE inhibitors described so far. Finally, incubation of oxidosqualene 3-(6S,7S) with purified SE led to the formation of dioxidosqualene 22-(3S,6S,7S), whereas its regioisomer 23-(3S,18S,19S) was not detected. In contrast, incubation of epoxide 3-(6R,7R) under the same conditions afforded a mixture of dioxides 22-(3S,6R,7R) and 23-(3S,18R,19R) in a 5:12 molar ratio. The fact that oxidosqualenes 3 and 4 have been found in nature, and our previous results showing that racemic dioxide 23 is a potent inhibitor of oxidosqualene-lanosterol cyclase in rat liver microsomes (Abad, J. L.; et al. J. Org. Chem. 1993, 58, 3991), confers a potential physiological relevance to the results reported herein.
• Production of epoxydammaranes by the enzymatic reactions of (3R)- and (3S)-2,3-squalene diols and those of 2,3:22,23-dioxidosqualenes with recombinant squalene cyclase and the mechanistic insight into the polycyclization reactions
  作者：Tsutomu Hoshino、Yukie Yonemura、Takamasa Abe、Yumi Sugino

  DOI：10.1039/b615897h

  日期：——

  The enzymatic cyclizations of (3R)- and (3S)-2,3-squalene diols by squalene cyclase afforded bicyclic compounds and epoxydamamranes in a ca. 3 : 2 ratio. Formation of the epoxydammarane scaffold indicates that a 6/6/6/5-fused tetracyclic cation is involved as the intermediate in the polycyclization reaction. 2,3:22,23-Dioxidosqualenes also afforded an epoxydammarane skeleton, i.e., 3α- or 3β-hydroxyepoxydammaranes, but the amount of bicyclic compounds produced was markedly lower than that of the squalene diols, indicating that the larger steric bulk of the diols had a more significant influence on the polycyclization pathway than the smaller bulk of the expoxide. All the epoxydammaranes had 17R,20R stereochemistry except for one product, demonstrating that these analogs were folded into an all-chair conformation in the reaction cavity. The mechanistic insight into the observed stereochemical specificities indicated that the organized all-chair conformation is rigidly constricted by squalene cyclase and, thus, free conformational change is not allowed inside the reaction cavity; a small rotation of the hydroxyl group or the epoxide toward the intermediary cation gave a high yield of the enzymatic products, while a large rotation led to a low yield of the product. The stereochemistries of the generated epoxydammaranes are opposite to those from natural sources, and thus almost all of the enzymatic products described here are novel.

  通过角鲨烯环化酶对(3R)-和(3S)-2,3-鲨烯二醇进行酶环化，可得到双环化合物和环氧达玛烷，两者的比例约为 3:2。环氧达玛烷支架的形成表明，6/6/6/5-融合的四环阳离子作为中间体参与了多环化反应。2,3:22,23-二氧二十二烷也能产生环氧达玛烷骨架，即 3α- 或 3β- 羟基环氧达玛烷，但产生的双环化合物的数量明显低于角鲨烯二醇，这表明二醇较大的立体体积对多环化途径的影响要大于较小的过氧化物体积。除一种产物外，所有环氧达玛烷都具有 17R、20R 立体化学结构，这表明这些类似物在反应腔中折叠成全椅构象。对所观察到的立体化学特异性的机理认识表明，有组织的全椅构象受到角鲨烯环化酶的严格限制，因此反应腔内不允许自由构象变化；羟基或环氧化物朝中间阳离子方向的微小旋转可产生高产率的酶促产物，而较大的旋转则导致产物的低产率。生成的环氧达玛烷的立体化学结构与天然来源的环氧达玛烷相反，因此这里描述的几乎所有酶产物都是新的。