(6S,7S)-squalene-6,7-epoxide

• 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: (6S,7S)-squalene-6,7-epoxide
• 英文别名: 6(S),7(S)-Oxidosqualene；(2S,3S)-2-methyl-2-(4-methylpent-3-enyl)-3-[(3E,7E,11E)-3,8,12,16-tetramethylheptadeca-3,7,11,15-tetraenyl]oxirane
• 化学式: C₃₀H₅₀O
• 分子量: 426.726
• InChiKey: ZBGRMKZSJNJFTN-RDYFRTLMSA-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：

  (6S,7S)-squalene-6,7-epoxide 在 aluminum isopropoxide 作用下， 以 甲苯 为溶剂， 反应 10.0h， 以2 mg的产率得到(10E,14E,18E)-(S)-2,10,15,19,23-Pentamethyl-6-methylene-tetracosa-2,10,14,18,22-pentaen-7-ol
  参考文献：
  名称：

  来自 Caulerpa prolifera 的三种角鲨烯衍生物

  摘要：

  摘要 (6S,7S)-Squalene-6,7-epoxide, (10S, 11S)-squalene-10,11-epoxide 和 all-trans-(3S)-2,6,10,15,19,23-hexamethyltetracosa -1,6,10,14,18,22-hexaen-3-ol 已从海藻 Caulerpa prolifera 中分离出来。

  DOI：

  10.1016/0031-9422(82)83189-0
• 作为产物：
  描述：

  Methanesulfonic acid (4E,8E,12E)-1-(1-hydroxy-1,5-dimethyl-hex-4-enyl)-4,9,13,17-tetramethyl-octadeca-4,8,12,16-tetraenyl ester 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 (6S,7S)-squalene-6,7-epoxide 、 6(R),7(R)-Oxidosqualenene
  参考文献：
  名称：

  Internal Oxidosqualenes: Determination of Absolute Configuration and Activity as Inhibitors of Purified Pig Liver Squalene Epoxidase

  摘要：

  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.

  DOI：

  10.1021/jo00117a014

文献信息

• Synthesis of (E)- and (Z)-29-methylidyne-2,3-oxidosqualene derivatives as inhibitors of liver and yeast oxidosqualene cyclase
  作者：Maurizio Ceruti、Franca Viola、Gianni Balliano、Paola Milla、Giorgio Roma、Giancarlo Grossi、Flavio Rocco

  DOI：10.1039/b200888m

  日期：2002.6.7

  derivatives is described starting from the C22 and C17 squalene aldehyde monobromohydrins. The conversion was achieved by means of a Wittig reaction, followed by desilylation of the terminal acetylene. For trisubstituted 1,3-enynes, preliminary alkylation with a suitable allyl bromide was performed. A new procedure for the synthesis of squalene aldehyde C27, C22 and C17 monobromohydrins is also described

  从C 22和C 17角鲨烯醛单溴醇开始描述（E）-和（Z）-29-亚甲基二炔-2,3-氧化角鲨烯衍生物的合成。借助于维蒂希反应（Wittig reaction），然后对末端乙炔进行甲硅烷基化来实现该转化。对于三取代的1，3-烯炔，用合适的烯丙基溴进行初步烷基化。还描述了用于合成鲨烯醛C 27，C 22和C 17一溴代醇的新方法。一些新化合物可作为猪肝和酵母氧化角鲨烯环化酶的抑制剂，并且是动物酶的时间依赖性抑制剂。
• Synthesis and biological activity of 19-azasqualene 2,3-epoxide as inhibitor of 2,3-oxidosqualene cyclase
  作者：M Ceruti、F Rocco、F Viola、G Balliano、G Grosa、F Dosio、L Cattel

  DOI：10.1016/0223-5234(93)90026-b

  日期：1993.1

  19-Azasqualene 2,3-epoxide and its N-oxide, high-energy intermediate analogue inhibitors of 2,3-oxidosqualene (SO) cyclase, were obtained by total synthesis. These compounds were designed to mimic the C-20 carbonium ion precursor of lanosterol formed during SO cyclization. The synthesis involved the preparation Of C22 squalenoid aldehyde epoxide through a new procedure and the reconstruction of the squalenoid chain bearing a nitrogen at C-19 (pro C-20). 19-Azasqualene 2,3-epoxide was active on SO cyclase from rat and pig liver with an IC50 of 1.5 muM in pig, while in SO cyclases of yeast (S cerevisiae and C albicans) microsomes it was 20-30-fold less active. It was inactive on squalene epoxidase from rat and pig liver at the highest concentrations tested (100 muM).
• 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.
• Three squalene derivatives from Caulerpa prolifera
  作者：Lorenzo De Napoli、Ernesto Fattorusso、Silvana Magno、Luciano Mayol

  DOI：10.1016/0031-9422(82)83189-0

  日期：——

  Abstract (6S,7S)-Squalene-6,7-epoxide, (10S, 11S)-squalene-10,11-epoxide and all-trans-(3S)-2,6,10,15,19,23-hexamethyltetracosa-1,6,10,14,18,22-hexaen-3-ol have been isolated from the marine alga Caulerpa prolifera.

  摘要 (6S,7S)-Squalene-6,7-epoxide, (10S, 11S)-squalene-10,11-epoxide 和 all-trans-(3S)-2,6,10,15,19,23-hexamethyltetracosa -1,6,10,14,18,22-hexaen-3-ol 已从海藻 Caulerpa prolifera 中分离出来。