(+)-(2R,3E)-4-(2',5'-dimethylphenyl)-but-3-en-2-ol

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂醇
• 英文名称: (+)-(2R,3E)-4-(2',5'-dimethylphenyl)-but-3-en-2-ol
• 英文别名: (E)-4-(2',5'-dimethylphenyl)but-3-en-2-ol；(R,E)‐4‐(2',5'‐dimethylphenyl)but‐3‐en‐2‐ol；(E,2R)-4-(2,5-dimethylphenyl)but-3-en-2-ol
• 化学式: C₁₂H₁₆O
• 分子量: 176.258
• InChiKey: AHXWLSFZJNVUKK-XUIVZRPNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (+)-(2R,3E)-4-(2',5'-dimethylphenyl)-but-3-en-2-ol 在 丙酸 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 27.0h， 生成 (-)-(3S,4E)-3-(2′,5′-dimethylphenyl)hex-4-enoic acid
  参考文献：
  名称：

  Chiral δ-iodo-γ-lactones derived from cuminaldehyde, 2,5-dimethylbenzaldehyde and piperonal: chemoenzymatic synthesis and antiproliferative activity

  摘要：

  Six enantiomeric pairs of beta-aryl-delta-iodo-gamma-lactones 8a-c, 9a-c derived from cuminaldehyde, 2,5-dimethylbenzaldehyde and piperonal were synthesized with high enantiomeric purities (ee 93-99%) from enantiomerically enriched allyl alcohols 3a-c. The key step in the synthesis of lactones 8a and 9a was the kinetic resolution of racemic (E)-4-(4'-isopropylphenyl)but-3-en-2-ol 3a by a lipase-catalysed transesterification. Among the five tested enzymes, the most effective and enantioselective was lipase B from Candida antarctica and after 2 h (-)-(S)-alcohol 3a and (+)-(R)-propionate 5 were obtained with ee's >= 99%. The transfer of chirality from alcohols (S)-3a-c and (R)-3a-c to gamma,delta-unsaturated esters (S)-6a-c and (R)-6a-c via a stereoselective Johnson-Claisen rearrangement followed by hydrolysis and iodolactonization afforded the final lactones 8a-c and 9a-c. The configurations of their stereogenic centres were assigned based on crystallographic analysis and/or the iodolactonization mechanism. In 42 of 48 tests, the synthesized lactones showed antiproliferative activity against four selected cancer lines (Jurkat, D17, GL-1, CLBL-1). The trans-stereoisomers were more active than the cis-stereoisomers and the highest activity was found for lactone (-)-trans-(4S,5R,6S)-9c with a 1,3-benzodioxole substituent and both enantiomers of the trans-lactone with a 2,5-dimethylphenyl substituent: (+)-9b and (-)-9b. Among the trans-lactones, those with a (4S,5R,6S)-configuration exhibited higher activity than their enantiomers and the most significant difference was observed for the enantiomers of the trans-lactone with a 1,3-benzodioxole substituent 9c (IC50 = 5.29 and 5.08 vs 36.47 and 33.77 for Jurkat and GL-1 cancer lines respectively). (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2016.02.003
• 作为产物：
  描述：

  (E)-4-(2,5-dimethylphenyl)-3-buten-2-one 在 sodium tetrahydroborate 、 Candida antarctica lipase immobilized on acrylic resin 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 异丙醚 、 水 为溶剂， 反应 16.0h， 生成 (+)-(2R,3E)-4-(2',5'-dimethylphenyl)-but-3-en-2-ol
  参考文献：
  名称：

  （E）-4-（2'，5'-二甲基苯基）-but-3-en-2-ol和（E）-4-（benzo [ d ] [1'，3'] dioxol-5的动力学拆分脂肪酶催化的酯交换反应合成'-基）-丁-3-烯-2-醇

  摘要：

  开发了一种短而有效的化学酶促途径，以生产两种立体异构形式的烯丙醇，其在立体异构中心具有庞大的芳族取代基，即（E）-4-（2'，5'-二甲基苯基）-but-3-en-2 -ol和（E）-4-（苯并[ d ] [1'，3']二恶醇-5'-基）-丁-3-烯-2-醇。醇经过脂肪酶催化的酯交换反应，南极假丝酵母（CAL-B）的脂肪酶被证明是筛选实验中最有效的生物催化剂，显示出对（R）-对映异构体的高度对映异构性。用乙酸异丙烯酯代替丙酸乙烯酯会降低所有脂肪酶催化的（E）-4-（苯并[ d]] [1'，3']二氧杂环戊烯-5'-基） -丁-3-烯-2-醇，但在CAL-B和Amano脂肪酶PS的两种制剂的情况下，对映选择率为显著增强（Ë > 100）。在（的制备规模反应ë）-4-（2'，5'-二甲基苯基） -丁-3-烯-2-醇与丙酸乙烯酯催化由CAL-B，未反应的（ - ） - （小号） -醇（EE = 98％）和（+）

  DOI：

  10.1016/j.tetasy.2015.05.006

文献信息

• Free and Immobilized Lecitase™ Ultra as the Biocatalyst in the Kinetic Resolution of (E)-4-Arylbut-3-en-2-yl Esters
  作者：Aleksandra Leśniarek、Anna Chojnacka、Radosław Drozd、Magdalena Szymańska、Witold Gładkowski

  DOI：10.3390/molecules25051067

  日期：——

  chain length was investigated for the enantioselective hydrolysis of racemic 4-arylbut-3-en-2-yl esters using Lecitase™ Ultra (LU). Immobilized preparations of the Lecitase™ Ultra enzyme had significantly higher activity and enantioselectivity than the free enzyme, particularly for 4-phenylbut-3-en-2-yl butyrate as the substrate. Moreover, the kinetic resolution with the immobilized enzyme was achieved

  使用 Lecitase™ Ultra (LU) 研究了缓冲液类型、共溶剂类型和酰基链长度对外消旋 4-芳基丁-3-烯-2-基酯的对映选择性水解的影响。Lecitase™ Ultra 酶的固定化制剂比游离酶具有显着更高的活性和对映选择性，特别是对于作为底物的 4-phenylbut-3-en-2-yl butyrate。此外，固定化酶的动力学分辨率在更短的时间内（24-48 小时）实现。Lecitase™ Ultra，固定在溴化氰活化的琼脂糖上，特别有效，在以丙酮为共溶剂的磷酸盐缓冲液 (pH 7.2) 中反应 24 小时后，产生 (R)-醇和未反应的 (S)-具有良好到极好的对映体过量（ee 90-99%）的酯。
• Chiral δ-iodo-γ-lactones derived from cuminaldehyde, 2,5-dimethylbenzaldehyde and piperonal: chemoenzymatic synthesis and antiproliferative activity
  作者：Witold Gładkowski、Andrzej Skrobiszewski、Marcelina Mazur、Anna Gliszczyńska、Marta Czarnecka、Aleksandra Pawlak、Bożena Obmińska-Mrukowicz、Gabriela Maciejewska、Agata Białońska

  DOI：10.1016/j.tetasy.2016.02.003

  日期：2016.4

  Six enantiomeric pairs of beta-aryl-delta-iodo-gamma-lactones 8a-c, 9a-c derived from cuminaldehyde, 2,5-dimethylbenzaldehyde and piperonal were synthesized with high enantiomeric purities (ee 93-99%) from enantiomerically enriched allyl alcohols 3a-c. The key step in the synthesis of lactones 8a and 9a was the kinetic resolution of racemic (E)-4-(4'-isopropylphenyl)but-3-en-2-ol 3a by a lipase-catalysed transesterification. Among the five tested enzymes, the most effective and enantioselective was lipase B from Candida antarctica and after 2 h (-)-(S)-alcohol 3a and (+)-(R)-propionate 5 were obtained with ee's >= 99%. The transfer of chirality from alcohols (S)-3a-c and (R)-3a-c to gamma,delta-unsaturated esters (S)-6a-c and (R)-6a-c via a stereoselective Johnson-Claisen rearrangement followed by hydrolysis and iodolactonization afforded the final lactones 8a-c and 9a-c. The configurations of their stereogenic centres were assigned based on crystallographic analysis and/or the iodolactonization mechanism. In 42 of 48 tests, the synthesized lactones showed antiproliferative activity against four selected cancer lines (Jurkat, D17, GL-1, CLBL-1). The trans-stereoisomers were more active than the cis-stereoisomers and the highest activity was found for lactone (-)-trans-(4S,5R,6S)-9c with a 1,3-benzodioxole substituent and both enantiomers of the trans-lactone with a 2,5-dimethylphenyl substituent: (+)-9b and (-)-9b. Among the trans-lactones, those with a (4S,5R,6S)-configuration exhibited higher activity than their enantiomers and the most significant difference was observed for the enantiomers of the trans-lactone with a 1,3-benzodioxole substituent 9c (IC50 = 5.29 and 5.08 vs 36.47 and 33.77 for Jurkat and GL-1 cancer lines respectively). (C) 2016 Elsevier Ltd. All rights reserved.
• Kinetic resolution of (E)-4-(2′,5′-dimethylphenyl)-but-3-en-2-ol and (E)-4-(benzo[d][1′,3′]dioxol-5′-yl)-but-3-en-2-ol through lipase-catalyzed transesterification
  作者：Witold Gładkowski、Anna Gliszczyńska、Monika Siepka、Marta Czarnecka、Gabriela Maciejewska

  DOI：10.1016/j.tetasy.2015.05.006

  日期：2015.7

  respectively. The kinetic resolution of (E)-4-(benzo[d][1′,3′]dioxol-5′-yl)-but-3-en-2-ol using isopropenyl acetate and CAL-B after 1 h gave (−)-(S)-alcohol (ee = 99%) and (+)-(R)-acetate (ee = 91%) in yields of 44% and 46%, respectively. (+)-(R)-Alcohols were obtained by the hydrolysis of the corresponding esters. Except for (+)-(R,E)-4-(benzo[d][1′,3′]dioxol-5′-yl)-but-3-en-2-ol, all enantiomerically

  开发了一种短而有效的化学酶促途径，以生产两种立体异构形式的烯丙醇，其在立体异构中心具有庞大的芳族取代基，即（E）-4-（2'，5'-二甲基苯基）-but-3-en-2 -ol和（E）-4-（苯并[ d ] [1'，3']二恶醇-5'-基）-丁-3-烯-2-醇。醇经过脂肪酶催化的酯交换反应，南极假丝酵母（CAL-B）的脂肪酶被证明是筛选实验中最有效的生物催化剂，显示出对（R）-对映异构体的高度对映异构性。用乙酸异丙烯酯代替丙酸乙烯酯会降低所有脂肪酶催化的（E）-4-（苯并[ d]] [1'，3']二氧杂环戊烯-5'-基） -丁-3-烯-2-醇，但在CAL-B和Amano脂肪酶PS的两种制剂的情况下，对映选择率为显著增强（Ë > 100）。在（的制备规模反应ë）-4-（2'，5'-二甲基苯基） -丁-3-烯-2-醇与丙酸乙烯酯催化由CAL-B，未反应的（ - ） - （小号） -醇（EE = 98％）和（+）