(2R,3S)-2,3-dihydroxy-4-oxo-N,N-dipropylbutanamide | 919480-30-1

• 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: (2R,3S)-2,3-dihydroxy-4-oxo-N,N-dipropylbutanamide
• 英文别名: (2R,3S)-2,3-dihydroxy-4-oxo-N,N-dipropylbutyramide；DHOB
• CAS: 919480-30-1
• 化学式: C₁₀H₁₉NO₄
• 分子量: 217.265
• InChiKey: ZTENCUORSXTVCO-RKDXNWHRSA-N

物化性质

• 沸点：
  372.2±42.0 °C(Predicted)
• 密度：
  1.137±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  77.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R,3S)-2,3-dihydroxy-4-oxo-N,N-dipropylbutanamide 在 indium 、 barium dihydroxide 、 臭氧 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 42.5h， 生成 (4S,5R,6R)-6-dipropylcarbamoyl-2-oxo-4,5,6-trihydroxy-hexanoic acid ammonium salt
  参考文献：
  名称：

  用于唾液酸醛缩酶的定向进化的筛选底物的合成：针对用于制备甲型流感唾液酸酶抑制剂类似物的定制酶。

  摘要：

  两种选择性异构筛选底物（4R，5R，6R）-和（4S，5R，6R）-6-二丙基氨基甲酰基-2-氧代-4,5,6-三羟基己酸的立体选择性合成描述了唾液酸醛缩酶。补充方法依赖于立体选择性铟介导的丙烯酸α-溴甲基丙烯酸乙酯向官能化醛的添加。用α-羟基醛，（2R，3R）-2,3-二羟基-4-氧代丁酸二丙酰胺进行螯合控制，合成产物（6R，5R，4S）-6-二丙基氨基甲酰基-2得到-亚甲基-4,5,6-三羟基己酸乙酯。相反，向（2R，3R）-N，N-二丙基-2,3-O-异亚丙基-4-氧代丁酰胺中添加立体化学结果与Felkin-Anh对照和抗加合物（4R，5R ，6R）-6-二丙基氨基甲酰基-2-亚甲基-4-羟基-5，主要产物6-O-异亚丙基-己酸乙酯。臭氧分解和脱保护以高收率得到了以呋喃糖和吡喃糖形式的混合物的筛选底物。

  DOI：

  10.1039/b501503k
• 作为产物：
  描述：

  (4R,5S)-5-Formyl-2,2-dimethyl-[1,3]dioxolane-4-carboxylic acid dipropylamide 在 正丁基锂 、 臭氧 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 21.53h， 生成 (2R,3S)-2,3-dihydroxy-4-oxo-N,N-dipropylbutanamide
  参考文献：
  名称：

  用于唾液酸醛缩酶的定向进化的筛选底物的合成：针对用于制备甲型流感唾液酸酶抑制剂类似物的定制酶。

  摘要：

  两种选择性异构筛选底物（4R，5R，6R）-和（4S，5R，6R）-6-二丙基氨基甲酰基-2-氧代-4,5,6-三羟基己酸的立体选择性合成描述了唾液酸醛缩酶。补充方法依赖于立体选择性铟介导的丙烯酸α-溴甲基丙烯酸乙酯向官能化醛的添加。用α-羟基醛，（2R，3R）-2,3-二羟基-4-氧代丁酸二丙酰胺进行螯合控制，合成产物（6R，5R，4S）-6-二丙基氨基甲酰基-2得到-亚甲基-4,5,6-三羟基己酸乙酯。相反，向（2R，3R）-N，N-二丙基-2,3-O-异亚丙基-4-氧代丁酰胺中添加立体化学结果与Felkin-Anh对照和抗加合物（4R，5R ，6R）-6-二丙基氨基甲酰基-2-亚甲基-4-羟基-5，主要产物6-O-异亚丙基-己酸乙酯。臭氧分解和脱保护以高收率得到了以呋喃糖和吡喃糖形式的混合物的筛选底物。

  DOI：

  10.1039/b501503k

文献信息

• Evaluation of fluoropyruvate as nucleophile in reactions catalysed by N-acetyl neuraminic acid lyase variants: scope, limitations and stereoselectivity
  作者：Jennifer Stockwell、Adam D. Daniels、Claire L. Windle、Thomas A. Harman、Thomas Woodhall、Tomas Lebl、Chi H. Trinh、Keith Mulholland、Arwen R. Pearson、Alan Berry、Adam Nelson

  DOI：10.1039/c5ob02037a

  日期：——

  The stereochemical course of aldolase-catalysed reaction between fluoropyruvate and aldehydes is described.

  描述了aldolase催化的氟代丙酮和醛之间的立体化学过程。

• Creation of a Pair of Stereochemically Complementary Biocatalysts
  作者：Gavin J. Williams、Thomas Woodhall、Lorna M. Farnsworth、Adam Nelson、Alan Berry

  DOI：10.1021/ja065233q

  日期：2006.12.1

  carbon-carbon formation, and as such, its utility as a catalyst for use in synthetic chemistry is limited. For example, the NAL-catalyzed condensation between pyruvate and (2R,3S)-2,3-dihydroxy-4-oxo-N,N-dipropylbutyramide yields ca. 3:1 mixtures of diastereomeric products under either kinetic or thermodynamic control. Engineering the stereochemical course of NAL-catalyzed reactions could remove this limitation

  N-乙酰神经氨酸裂合酶 (NAL) 在碳-碳形成过程中表现出较差的面部选择性，因此，其作为催化剂在合成化学中的应用受到限制。例如，丙酮酸和 (2R,3S)-2,3-dihydroxy-4-oxo-N,N-dipropylbutyramide 之间的 NAL 催化缩合产生 ca。在动力学或热力学控制下的非对映体产物的 3:1 混合物。设计 NAL 催化反应的立体化学过程可以消除这一限制。我们使用定向进化来创建一对立体化学互补变体 NAL，用于合成唾液酸模拟物。E192N 变体是一种高效催化剂，用于 (2R,3S)-2,3-dihydroxy-4-oxo-N,N-dialkylbutyramides 的羟醛反应，被选为起点。原来，容易出错的 PCR 鉴定了 NAL 活性位点中的残基，这些残基有助于醛缩酶催化反应的立体化学控制。随后，使用饱和和定点诱变的强烈结构引导程序来鉴定互补的变体对 E192N/T167G
• Development of an organo- and enzyme-catalysed one-pot, sequential three-component reaction
  作者：Angela Kinnell、Thomas Harman、Matilda Bingham、Alan Berry、Adam Nelson

  DOI：10.1016/j.tet.2012.02.010

  日期：2012.9

  A one-pot, three-component process is described which involves both organo- and enzyme-catalysed carbon-carbon bond-forming steps. In the first step, an organocatalyst catalyses the aldol reaction between acetaldehyde and a glyoxylamide. After dilution with additional aqueous buffer, and addition of pyruvate and an aldolase enzyme variant, a second aldol reaction occurs to yield a final product. Crucially, it was possible to develop a reaction in which both the organo- and enzyme-catalysed reactions could be performed in the same aqueous buffer system. The reaction described is the first example of a one-pot, three-component reaction in which the two carbon-carbon bond-forming processes are catalysed using the combination of an organocatalyst and an enzyme. (C) 2012 Elsevier Ltd. All rights reserved.
• Creation of a Tailored Aldolase for the Parallel Synthesis of Sialic Acid Mimetics
  作者：Thomas Woodhall、Gavin Williams、Alan Berry、Adam Nelson

  DOI：10.1002/anie.200462733

  日期：2005.3.29
• Structural Insights into Substrate Specificity in Variants of N-Acetylneuraminic Acid Lyase Produced by Directed Evolution
  作者：Ivan Campeotto、Amanda H. Bolt、Thomas A. Harman、Caitriona Dennis、Chi H. Trinh、Simon E.V. Phillips、Adam Nelson、Arwen R. Pearson、Alan Berry

  DOI：10.1016/j.jmb.2010.08.008

  日期：2010.11

  The substrate specificity of Escherichia coli N-acetylneuraminic acid lyase was previously switched from the natural condensation of pyruvate with N-acetylmannosamine, yielding N-acetylneuraminic acid, to the aldol condensation generating N-alkylcarboxamide analogues of N-acetylneuraminic acid. This was achieved by a single mutation of Glu192 to Asn. In order to analyze the structural changes involved and to more fully understand the basis of this switch in specificity, we have isolated all 20 variants of the enzyme at position 192 and determined the activities with a range of substrates. We have also determined five high-resolution crystal structures: the structures of wild-type E. coli N-acetylneuraminic acid lyase in the presence and in the absence of pyruvate, the structures of the E192N variant in the presence and in the absence of pyruvate, and the structure of the E192N variant in the presence of pyruvate and a competitive inhibitor (2R,3R)-2,3,4-trihydroxy-N,N-dipropylbutanamide. All structures were solved in space group P2(1) at resolutions ranging from 1.65 Å to 2.2 Å. A comparison of these structures, in combination with the specificity profiles of the variants, reveals subtle differences that explain the details of the specificity changes. This work demonstrates the subtleties of enzyme-substrate interactions and the importance of determining the structures of enzymes produced by directed evolution, where the specificity determinants may change from one substrate to another.