6-[(3R,4S,5S,7R,8S,9S)-7-ethyl-10-[(2R,3R)-2-ethyl-3-[2-[(2R,3R)-2-ethyl-3-methyloxiran-2-yl]ethyl]oxiran-2-yl]-4,8-dihydroxy-3,5,9-trimethyl-6-oxodecyl]-2-hydroxy-3-methylbenzoic acid | 1056032-77-9

• 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: 6-[(3R,4S,5S,7R,8S,9S)-7-ethyl-10-[(2R,3R)-2-ethyl-3-[2-[(2R,3R)-2-ethyl-3-methyloxiran-2-yl]ethyl]oxiran-2-yl]-4,8-dihydroxy-3,5,9-trimethyl-6-oxodecyl]-2-hydroxy-3-methylbenzoic acid
• CAS: 1056032-77-9
• 化学式: C₃₄H₅₄O₈
• 分子量: 590.798
• InChiKey: GZSVXEOFOIBCNR-QSGZZWGISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  42
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  140
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  benzyl 6-[(3R,4S,5S,7R,8S,9S)-7-ethyl-10-[(2R,3R)-2-ethyl-3-[2-[(2R,3R)-2-ethyl-3-methyloxiran-2-yl]ethyl]oxiran-2-yl]-4,8-dihydroxy-3,5,9-trimethyl-6-oxodecyl]-3-methyl-2-phenylmethoxybenzoate 在 Pd(OH)2/C 、 水 、 碳酸氢铵 作用下， 以 甲醇 为溶剂， 反应 0.17h， 以3%的产率得到6-[(3R,4S,5S,7R,8S,9S)-7-ethyl-10-[(2R,3R)-2-ethyl-3-[2-[(2R,3R)-2-ethyl-3-methyloxiran-2-yl]ethyl]oxiran-2-yl]-4,8-dihydroxy-3,5,9-trimethyl-6-oxodecyl]-2-hydroxy-3-methylbenzoic acid
  参考文献：
  名称：

  Epoxide Hydrolase Lsd19 for Polyether Formation in the Biosynthesis of Lasalocid A: Direct Experimental Evidence on Polyene-Polyepoxide Hypothesis in Polyether Biosynthesis

  摘要：

  Polyether metabolites are an important class of natural products. Although their biosynthesis, especially construction of polyether skeletons, attracted organic chemists for many years, no experimental data on the enzymatic polyether formation has been obtained. In this study, a putative epoxide hydrolase gene lsd19 found on the biosynthetic gene cluster of an ionophore polyether lasalocid was cloned and successfully overexpressed in Escherichia coli. Using the purified Lsd19, a proposed substrate, bisepoxyprelasalocid, and its synthesized analogue were successfully converted into lasalocid A and its derivative via a 6-endo-tet cyclization mode. On the other hand, treatment of the bisepoxide with trichloroacetic acid gave isolasalocid A via a 5-exo-tet cyclization mode. Therefore, the enzymatic conversion observed in this study unambiguously showed that the bisepoxyprelasalocid is an intermediate of the lasalocid biosynthesis and that Lsd19 catalyzes the sequential cyclic ether formations involving an energetically disfavored 6-endo-tet cyclization. This is the first example of the enzymatic epoxide-opening reactions leading to a polyether natural product.

  DOI：

  10.1021/ja8040543

文献信息

• Epoxide Hydrolase Lsd19 for Polyether Formation in the Biosynthesis of Lasalocid A: Direct Experimental Evidence on Polyene-Polyepoxide Hypothesis in Polyether Biosynthesis
  作者：Yoshihiro Shichijo、Akira Migita、Hiroki Oguri、Mami Watanabe、Tetsuo Tokiwano、Kenji Watanabe、Hideaki Oikawa

  DOI：10.1021/ja8040543

  日期：2008.9.17

  Polyether metabolites are an important class of natural products. Although their biosynthesis, especially construction of polyether skeletons, attracted organic chemists for many years, no experimental data on the enzymatic polyether formation has been obtained. In this study, a putative epoxide hydrolase gene lsd19 found on the biosynthetic gene cluster of an ionophore polyether lasalocid was cloned and successfully overexpressed in Escherichia coli. Using the purified Lsd19, a proposed substrate, bisepoxyprelasalocid, and its synthesized analogue were successfully converted into lasalocid A and its derivative via a 6-endo-tet cyclization mode. On the other hand, treatment of the bisepoxide with trichloroacetic acid gave isolasalocid A via a 5-exo-tet cyclization mode. Therefore, the enzymatic conversion observed in this study unambiguously showed that the bisepoxyprelasalocid is an intermediate of the lasalocid biosynthesis and that Lsd19 catalyzes the sequential cyclic ether formations involving an energetically disfavored 6-endo-tet cyclization. This is the first example of the enzymatic epoxide-opening reactions leading to a polyether natural product.