ethyl (3R,5S)-3,5-dihydroxy-6-benzyloxyhexanoate | 92757-82-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl (3R,5S)-3,5-dihydroxy-6-benzyloxyhexanoate
• 英文别名: ethyl 3R,5S-6-(benzyloxy)-3,5-dihydroxy hexanoate；(3r,5s)-Ethyl 6-(benzyloxy)-3,5-dihydroxyhexanoate；ethyl (3R,5S)-3,5-dihydroxy-6-phenylmethoxyhexanoate
• CAS: 92757-82-9
• 化学式: C₁₅H₂₂O₅
• 分子量: 282.337
• InChiKey: MVKCDWFSCUHMCH-KGLIPLIRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  20
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl (3R,5S)-3,5-dihydroxy-6-benzyloxyhexanoate 在 sodium hydroxide 、 甲苯 作用下， 以 1,4-二氧六环 为溶剂， 生成 (4R,6S)-6-(benzyloxy)methyl-4-hydroxy-tetrahydro-2-pyrone
  参考文献：
  名称：

  Asymmetric synthesis of (3R-)-and (3S-)-hydroxy-5-pentanolides

  摘要：

  DOI：

  10.1016/s0040-4039(01)91028-7
• 作为产物：
  描述：

  (-)-(2S,3R)-2,3-epoxy-4-(benzyloxy)-1-butanol 在 吡啶 、 咪唑 、 4 A molecular sieve 、 四丁基氟化铵 、 氯化二乙基铝 、 溶剂黄146 、 红铝 、 pyridinium chlorochromate 、 三氟乙酸 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 ethyl (3R,5S)-3,5-dihydroxy-6-benzyloxyhexanoate
  参考文献：
  名称：

  Asymmetric synthesis of (3R-)-and (3S-)-hydroxy-5-pentanolides

  摘要：

  DOI：

  10.1016/s0040-4039(01)91028-7

文献信息

• Stereoselective introduction of two chiral centers by a single diketoreductase: an efficient biocatalytic route for the synthesis of statin side chains
  作者：Xuri Wu、Lili Wang、Shuzhen Wang、Yijun Chen

  DOI：10.1007/s00726-009-0390-0

  日期：2010.6

  (Lipitor®), are the top-selling drugs in the world. The biocatalytic production of chiral side chains of statin drugs is of great interest to academia and industry. Stereoselective double reduction of a β,δ-diketo ester catalyzed by a diketoreductase offers a simple and efficient route for the preparation of statin side chains. Comparison of different cofactor regeneration systems resulted in an easy and cost-effective

  他汀类药物，包括阿托伐他汀（立普妥®），是最畅销的药物在世界上。他汀类药物的手性侧链的生物催化生产引起学术界和工业界的极大兴趣。双酮还原酶催化的β，δ-二酮酯的立体选择性双还原为他汀类侧链的制备提供了一种简单而有效的途径。不同辅因子再生系统的比较导致了这种酶促还原的简便且经济高效的过程。
• Synthesis of ethyl and t-butyl (3R,5S)-dihydroxy-6-benzyloxy hexanoates via diastereo- and enantioselective microbial reduction
  作者：Zhiwei Guo、Yijun Chen、Animesh Goswami、Ronald L. Hanson、Ramesh N. Patel

  DOI：10.1016/j.tetasy.2006.05.027

  日期：2006.6

  Previously we have demonstrated the reduction of ethyl diketoester 4 to the corresponding dihydroxy ester 6a by Acinetobacter sp. SC13874. Recently we screened more than 100 cultures for microbial reduction of both the ethyl and t-butyl diketoesters 4 and 5. Most yeast cultures showed a preference for reduction at the C-3 with low enantioselectivity. Among the three Acinetobacter strains screened, Acinetobacter sp. SC13874 reduced both compounds 4 and 5 to the corresponding (3R)- and (5S)-monohydroxy compounds. Monohydroxy compounds were isolated and their absolute configurations determined. (3R)- and (5S)-Monohydroxy compounds were reduced further to the corresponding dihydroxy esters 6a and 8a to provide alternate routes for the synthesis of compounds 14a nd 16a, potential intermediates for the synthesis of HMG-CoA reductase inhibitors. Cell suspensions of Acinetobacter sp. SC13874 reduced the ethyl diketoester 4 to a mixture of desired syn and undesired anti diastereomers. The desired syn-(3R,5S)-dihydroxy ester 6a was obtained with an enantiomeric excess (ee) of 99% and a diastereomeric excess (de) of 63%. Cell suspensions reduced the t-butyl diketoester 5 to a mixture of mono- and dihydroxy esters with the dihydroxy ester showing an ee of 87% and de of 51% for the desired syn(3R,5S)-dihydroxy ester 8a. Three different ketoreductases were purified to homogeneity, and their biochemical properties compared. Reductase I only catalyzes the reduction of ethyl diketoester 4 to its monohydroxy products 10 and 11, whereas reductase II catalyzes the formation of dihydroxy products 6 and 7 from monohydroxy substrates 10 and 11. A third reductase (III) was identified, which catalyzes the reduction of diketoester 4 to syn-(3R,5S)-dihydroxy ester 6a. (c) 2006 Elsevier Ltd. All rights reserved.