(R)-solketal butyrate | 57415-99-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (R)-solketal butyrate
• 英文别名: Butanoic acid, [(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl ester；[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl butanoate
• CAS: 57415-99-3
• 化学式: C₁₀H₁₈O₄
• 分子量: 202.251
• InChiKey: JMMOQNCIYAMRDB-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-solketal butyrate 生成 (R)-(-)-甘油醇缩丙酮
  参考文献：
  名称：

  KLOOSTERMAN, M.;MOSMULLER, E. W. J.;SCHOEMAKER, H. E.;MEIJER, E. M., TETRAHEDRON LETT., 28,(1987) N 26, 2989-2992

  摘要：

  DOI：
• 作为产物：
  描述：

  丙酮缩甘油 在 4-二甲氨基吡啶 、 rhizopus oryzae lipase 、 BES buffer 、 水 、 sodium carbonate 、 Triton X-100 作用下， 以 乙酸乙酯 为溶剂， 反应 16.5h， 生成 (R)-solketal butyrate
  参考文献：
  名称：

  Quantitative Screening of Hydrolase Libraries Using pH Indicators: Identifying Active and Enantioselective Hydrolases

  摘要：

  The slowest step in finding a selective hydrolase for synthesis is often the screening step. Researchers must run small test reactions and measure the amounts of stereoisomers formed by HPLC, GC, or NMR, We have developed a colorimetric method to speed up this screening. We quantitatively detect ester hydrolysis using a pH indicator, 4-nitrophenol. We estimate the selectivity by measuring the initial rates of hydrolysis for pure stereoisomers separately. To demonstrate the utility of this method, we screened seventy-two commercial enzymes for enantioselective hydrolysis of racemic solketal butyrate, an important chiral building block. First, we eliminated the twenty hydrolases that did not catalyze hydrolysis of either enantiomer. Next, we measured initial rates of hydrolysis of the pure enantiomers of solketal butyrate. For horse-liver esterase, these initial rates differed by a factor of twelve. Subsequent GC experiments confirmed an enantiomeric ratio of fifteen for this hydrolase, Although this enantioselectivity is moderate, it is the highest enantioselectivity reported for a hydrolysis of solketal esters.

  DOI：

  10.1002/(sici)1521-3765(19981102)4:11<2324::aid-chem2324>3.0.co;2-i

文献信息

• Mapping the substrate selectivity of new hydrolases using colorimetric screening: lipases from Bacillus thermocatenulatus and Ophiostoma piliferum, esterases from Pseudomonas fluorescens and Streptomyces diastatochromogenes
  作者：Andrew Man Fai Liu、Neil A Somers、Romas J Kazlauskas、Terry S Brush、Frank Zocher、Markus M Enzelberger、Uwe T Bornscheuer、Geoff P Horsman、Alessandra Mezzetti、Claudia Schmidt-Dannert、Rolf D Schmid

  DOI：10.1016/s0957-4166(01)00072-6

  日期：2001.3

  screened a general library of 29 substrates and a chiral library of 23 pairs of enantiomers. All four hydrolases catalysed the hydrolysis of unnatural substrates, but the two lipases accepted a broader range of substrates than the two esterases. As expected, the two lipases favoured more hydrophobic substrates, while the two esterases showed a preference for smaller substrates. Several moderately enantioselective

  生物化学和分子生物学的最新进展简化了新型水解酶的发现和制备。尽管这些水解酶可能解决了有机合成中的问题，但测量其选择性（尤其是对映选择性）仍然繁琐且耗时。最近，我们开发了一种比色筛选方法来测量水解酶的对映选择性。在这里，我们应用这种快速筛选方法来绘制四种新型水解酶的底物选择性图：来自嗜热芽孢杆菌的脂肪酶（DSM 730，BTL2）和丝状真菌Ophiostoma piliferum（NRRL 18917，OPL）以及来自两种细菌荧光假单胞菌（Pseudomonas fluorescens（ SIK-W1，酯酶I，PFE）和链霉菌（Tü20，SDE）。我们筛选了29种底物的通用文库和23对对映异构体的手性文库。所有四种水解酶均催化非天然底物的水解，但是与两种酯酶相比，两种脂肪酶接受的底物范围更广。不出所料，这两种脂肪酶偏爱疏水性更高的底物，而两种酯酶则偏爱较小的底物。确认了该酚醛酸酯的一些中等对映选择性反应：BTL2，丁酸酯，E
• Lipases Aided Esterification of (2,2-Dimethyl-1,3-dioxolan-4-yl)methanol
  作者：Aurelia Zniszczol、Krzysztof Walczak

  DOI：10.2174/157017861101140113155507

  日期：2014.1.31

  Racemic solketal (2,2-Dimethyl-1,3-dioxolan-4-yl)methanol 1, was treated with carboxylic acids of varying chain length or their vinyl esters in the presence of different lipases. The esterification reaction was carried out in n-hexane or diisopropyl ether as a solvent. The yield of the solketal esters and their enantiopurity were satisfactory, as indicated by gas chromatography using chiral column. Lipases from Rhizopus oryzae and Pseudomonas fluorescence gave the best enantiomeric excess (ee) when the solketal was treated with vinyl butyrate in a solution of diisopropyl ether at room temperature.

  消旋的索克替醛（2,2-二甲基-1,3-二恶烷-4-基）甲醇1，在不同脂肪酶的存在下，与不同链长的羧酸或其乙烯酯反应。酯化反应在正己烷或二异丙基醚中进行。索克替醛酯的产率和它们的手性纯度令人满意，这一点通过使用手性柱的气相色谱法得到了证实。来自米麹霉和荧光假单胞菌的脂肪酶在索克替醛与乙烯丁酸酯在室温下的二异丙基醚溶液中反应时，给出了最佳的对映体过量（ee值）。
• Differential Elimination of Synthetic Butyric Triglycerides In Vivo: A Pharmacokinetic Study
  作者：P. Planchon、P. Pouillart、G. Ronco、P. Villa、F. Pieri

  DOI：10.1002/jps.2600821016

  日期：1993.10

  New butyrate derivatives were synthesized to investigate the residence time of potent butyric acid in vivo. These derivatives were triglycerides in which one, two, or three butyric acid molecules were bound to glycerol or to mono- and dipalmitic esters of glycerol. Pharmacokinetic studies showed that a constant plasma level of each compound was maintained for a long time; all molecules had identical

  合成了新的丁酸酯衍生物，以研究强丁酸在体内的停留时间。这些衍生物是甘油三酸酯，其中一个，两个或三个丁酸分子与甘油或甘油的单和二棕榈酸酯结合。药代动力学研究表明，每种化合物的血浆水平可长期维持不变；所有分子的分布体积相同，但平均停留时间不同。存在棕榈酸的三酯没有毒性，并且在生物体中似乎更稳定。这可能是由于它们在组织上的吸附。可以合成由丁酸和各种长脂肪酸组成的其他甘油三酸酯，并在长期临床治疗中有用。
• An Esterase with Superior Activity and Enantioselectivity towards 1,2-<i>O</i>-Isopropylideneglycerol Esters Obtained by Protein Design
  作者：Luis F. Godinho、Carlos R. Reis、Ronald van Merkerk、Gerrit J. Poelarends、Wim J. Quax

  DOI：10.1002/adsc.201200211

  日期：2012.11.12

  selected as targets for mutagenesis, in order to enhance YbfF activity and enantioselectivity towards IPG esters. Random mutagenesis at positions 25, 124, 185 and 235 yielded several best YbfF variants with enhanced activity and enantioselectivity towards IPG esters. The best YbfF mutant, W235I, exhibited a 2-fold higher enantioselectivity than wild-type YbfF, with an E=38 for IPG butyrate and an E=77

  的大肠杆菌酯酶YbfF显示高朝1,2-活性ø -isopropylideneglycerol（IPG）丁酸酯和辛酸IPG，和更喜欢ř这些底物对映体，产生š超过IPG产物的对映体。为了提高该酶用于动力学拆分IPG的外消旋酯的潜力，非常需要提高活性和对映选择性。R的分子对接两种IPG酯的对映体都进入YbfF的活性位点，从而鉴定了近端的YbfF活性位点残基。选择四个残基（25、124、185和235）作为诱变目标，以增强YbfF活性和对IPG酯的对映选择性。在位置25、124、185和235处进行随机诱变产生了几种最佳的YbfF变体，具有增强的活性和对IPG酯的对映选择性。最好YbfF突变体，W235I，表现出2倍与更高的对映选择性比野生型YbfF，Ë用于IPG丁酸和= 38 È对于IPG辛酸酯＝ 77。分子对接实验进一步支持了实验显示的增强的对映选择性，并提供了该氨基酸取代对YbfF活性位点的
• Low-temperature method for enhancement of enantioselectivity in the lipase-catalyzed kinetic resolutions of solketal and some chiral alcohols
  作者：Takashi Sakai、Tetsuo Kishimoto、Yukie Tanaka、Tadashi Ema、Masanori Utaka

  DOI：10.1016/s0040-4039(98)01747-x

  日期：1998.10

  Low-temperature method (−40 °C at best) for enhancement of the enantioselectivity in a lipase-catalyzed transesterification was proved to be widely applicable to primary and secondary alcohols and enabled theoretical prediction of the course of enhancement of the enantioselectivity physicochemically.

  事实证明，在脂肪酶催化的酯交换反应中提高对映选择性的低温方法（最高为-40°C）已广泛适用于伯醇和仲醇，并能够从理论上预测物理化学上对映选择性提高的过程。