2-azido-3-hydroxy-propionaldehyde | 132803-72-6

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 2-azido-3-hydroxy-propionaldehyde
• 英文别名: 2-Azido-3-hydroxypropanal
• CAS: 132803-72-6
• 化学式: C₃H₅N₃O₂
• 分子量: 115.092
• InChiKey: POOKJRCUOSJKOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  8
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  51.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-azido-3-hydroxy-propionaldehyde 、 1-羟基-2-丁酮 在 fructose-6-phosphate aldolase sodium borate buffer 作用下， 以 甲苯 为溶剂， 反应 6.0h， 生成 (4S,5R,6R)-6-azido-4,5,7-trihydroxyheptan-3-one
  参考文献：
  名称：

  d-Fructose-6-Phosphate Aldolase-Catalyzed One-Pot Synthesis of Iminocyclitols

  摘要：

  A one-pot chemoenzymatic method for the synthesis of a variety of new iminocyclitols from readily available, non-phosphorylated donor substrates has been developed. The method utilizes the recently discovered fructose-6-phosphate aldolase (FSA), which is functionally distinct from known aldolases in its tolerance of different donor substrates as well as acceptor substrates. Kinetic studies were performed with dihydroxyacetone (DHA), the presumed endogenous substrate for FSA, as well as hydroxy acetone (HA) and 1-hydroxy-2-butanone (HB) as donor substrates, in each case using glyceraidehyde-3-phosphate as acceptor substrate. Remarkably, FSA used the three donor substrates with equal efficiency, with k(cat)/K-M-values of 33, 75, and 20 M-1 s(-1), respectively. This level of donor substrate tolerance is unprecedented for an aldolase. Furthermore, DHA, HA, and HB were accepted as donors in FSA-catalyzed aldol reactions with a variety of azido- and Cbz-amino aldehyde acceptors. The broad substrate tolerance of FSA and the ability to circumvent the need for phosphorylated substrates allowed for one-pot synthesis of a number of known and novel iminocyclitols in good yields, and in a very concise fashion. New iminocyclitols were assayed as inhibitors against a panel of glycosidases. Compounds 15 and 16 were specific alpha-mannosidase inhibitors, and 24 and 26 were potent and selective inhibitors of beta-N-acetylglucosaminidases in the submicromolar range. Facile access to these compounds makes them attractive core structures for further inhibitor optimization.

  DOI：

  10.1021/ja073911i
• 作为产物：
  描述：

  3-叠氮丁烷-1,2,4-三醇 在 sodium periodate 作用下， 以 水 为溶剂， 生成 2-azido-3-hydroxy-propionaldehyde
  参考文献：
  名称：

  Use of dihydroxyacetone phosphate-dependent aldolases in the synthesis of deoxy aza sugars

  摘要：

  The use of fructose-1,6-diphosphate (FDP), fuculose-1-phosphate (Fuc-1-P) and rhamnulose-1-phosphate (Rham-1-P) aldolases in organic synthesis is described. Fuc-1-P, Rham-1-P, and their phosphate-free species have been prepared and characterized. Both Fuc-1-P and Rham-1-P aldolases accept 3-azido-2-hydroxypropanal as a substrate to form L-omega-azidoketose phosphates, which upon dephosphorylation and hydrogenolysis on Pd/C, gave 1-deoxyazasugars structurally related to D-galactose and L-mannose. Hydrogenolysis of the enzyme products azidoketose 1-phosphates, however, gave 1,6-dideoxyazasugars structurally related to 6-deoxygalactose and L-rhamnose. Explanations for the stereoselectivity in the hydrogenolysis reactions were provided. Similarly, FDP aldolase catalyzed the aldol condensation reaction with 2-azido-3-hydroxypropanal to afford a new synthesis of 2(R),5(S)-bis(hydroxymethyl)-3(R),4(R)-dihydroxypyrrolidine, a potent inhibitor of a number of glycosidases. A new empirical formula is developed to relate the inhibition constants and inhibitor binding for alpha- and beta-glucosidases.

  DOI：

  10.1021/jo00022a013

文献信息

• Borate as a Phosphate Ester Mimic in Aldolase-Catalyzed Reactions: Practical Synthesis ofL-Fructose andL-Iminocyclitols
  作者：Masakazu Sugiyama、Zhangyong Hong、Lisa J. Whalen、William A. Greenberg、Chi-Huey Wong

  DOI：10.1002/adsc.200600356

  日期：2006.12

  Dihydroxyacetone phosphate (DHAP)-dependent aldolases have been widely used for the organic synthesis of unnatural sugars or derivatives. The practicality of using DHAP-dependent aldolases is limited by their strict substrate specificity and the high cost and instability of DHAP. Here we report that the DHAP-dependent aldolase L-rhamnulose 1-phosphate aldolase (RhaD) accepts dihydroxyacetone (DHA)

  磷酸二羟基丙酮（DHAP）依赖性醛缩酶已广泛用于非天然糖或衍生物的有机合成。使用依赖DHAP的醛缩酶的实用性受到其严格的底物特异性以及DHAP的高成本和不稳定性的限制。在这里我们报告依赖DHAP的醛缩酶L-鼠李糖1-磷酸醛缩酶（RhaD）在硼酸盐缓冲液的存在下接受二羟基丙酮（DHA）作为供体底物，大概是通过原位可逆的形成DHA硼酸酯。该反应似乎是不可逆的，热力学上将产物捕获为硼酸盐配合物。我们已经将该发现用于开发非热量甜味剂L-果糖的实用一步合成。在RhaD存在下，由消旋甘油醛和DHA合成L-果糖，硼酸盐的克收率为92％。我们还分两步合成了一系列L-亚氨基环糖醇，它们是潜在的糖苷酶抑制剂。
• Structure-based rationalization of aldolase-catalyzed asymmetric synthesis
  作者：Junjie Liu、Grace DeSantis、Chi-Huey Wong

  DOI：10.1139/v02-094

  日期：2002.6.1

  This paper describes a structure-based approach to elucidate the stereospecificity, including inversion of enantioselectivity, of the 2-deoxyribose-5-phosphate aldolase-catalyzed asymmetric aldol addition reaction using unnatural substrates designed for the total synthesis of epothilones. In addition, an aldolase variant with Ser-238 being altered for Asp was found to be 2.5 times more effective than the wild type in accepting the unphosphorylated substrate D-glyceraldehyde. A new H-bonding interaction between the Asp-238 carboxylate and the 3-hydroxyl of the substrate was identified and was used to rationalize the rate enhancements.Key words: aldol reaction, 2-deoxyribose-5-phosphate aldolase, mutagenesis, inversion of enantioselectivity.

  这篇文章描述了一种基于结构的策略，用于阐明2-脱氧核糖-5-磷酸醛缩酶催化的不对称醛缩加成反应的立体特异性，包括外消旋选择性反转，使用为伊波泰隆全合成设计的非自然底物。此外，一种将Ser-238变为Asp的醛缩酶变异体在接纳非磷酸化底物D-甘油醛方面比野生型有效2.5倍。发现了一种新的氢键相互作用，即Asp-238羧基与底物3-羟基之间的相互作用，并用于合理解释速率提升。关键词：醛缩反应，2-脱氧核糖-5-磷酸醛缩酶，突变，外消旋选择性反转。
• Chemoenzymatic Preparation of Novel Cyclic Imine Sugars and Rapid Biological Activity Evaluation Using Electrospray Mass Spectrometry and Kinetic Analysis
  作者：Shuichi Takayama、Richard Martin、Jiangyue Wu、Karen Laslo、Gary Siuzdak、Chi-Huey Wong

  DOI：10.1021/ja971695f

  日期：1997.9.1

  and since imines are key intermediates in a variety of cycloadditions, condensations, and nucleophilic additions, they are valuable as versatile synthetic intermediates for the preparation of novel iminocyclitols and derivatives. An example of such synthetic utility is demonstrated by the synthesis of amino-iminocyclitol 24 via a three-center, two-component Strecker reaction. A novel method for rapidly

  环状亚胺糖是通过一种新的化学酶促策略制备的，其中通过酶促醛醇反应构建的叠氮糖在酸性条件下氢化。发现这些环状亚胺糖是糖加工酶的有效抑制剂，这些酶对多种糖苷酶的 Ki 值在纳摩尔和微摩尔范围内。与它们完全氢化的对应物相比，环状亚胺糖通常对所测试的糖苷酶表现出相当或更好的抑制作用。由于这些环状亚胺很容易获得，并且由于亚胺是各种环加成、缩合和亲核加成的关键中间体，因此它们作为用于制备新型亚氨基环醇和衍生物的通用合成中间体是有价值的。通过三中心、两组分 Strecker 反应合成氨基-亚氨基环醇 24 证明了这种合成效用的一个例子。一种使用电喷雾快速筛选糖苷酶抑制剂的新方法...
• 2-methyl-5-hydroxymethyl- and 2,5-dimethyl-3,4-dihydroxypyrrolidines
  申请人：The Scripps Research Institute

  公开号：US05229523A1

  公开（公告）日：1993-07-20

  2-Methyl-5-hydroxymethyl- and 2,5-dimethyl-3,4-dihydroxypyrrolidines, 2,5-dimethyl-3,4-dihydroxypyrrolidines, their processes of preparation and use are disclosed. 5-Azido-5-deoxyhexulose-1-phosphate compounds and processes of making the same are also disclosed.

  本发明公开了2-甲基-5-羟甲基和2,5-二甲基-3,4-二羟基吡咯烷，2,5-二甲基-3,4-二羟基吡咯烷的制备方法和用途。同时，还公开了5-偶氮-5-脱氧己糖酮-1-磷酸化合物及其制备方法。
• Aldolase enzyme process for making 5-azido-5-deoxy-hexulose-1-phosphate
  申请人：The Scripps Research Institute

  公开号：US05352591A1

  公开（公告）日：1994-10-04

  2-Methyl-5-hydroxymethyl-and 2,5-dimethyl-3,4-dihydroxypyrrolidines, their processes of preparation and use are disclosed. 5-Azido-5-deoxy-hexulose-1-phosphate compounds and processes of making the same are also disclosed.

  本发明公开了2-甲基-5-羟甲基和2,5-二甲基-3,4-二羟基吡咯烷的制备和使用方法。还公开了5-偶氮基-5-脱氧-己糖酮-1-磷酸盐化合物及其制备方法。