(2S,3R)-2-Amino-3-hydroxy-4-(4-methoxyphenyl)butanoic acid | 157457-72-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,3R)-2-Amino-3-hydroxy-4-(4-methoxyphenyl)butanoic acid
• CAS: 157457-72-2
• 化学式: C₁₁H₁₅NO₄
• 分子量: 225.244
• InChiKey: LFFIXBOLXCYHMK-ZJUUUORDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  92.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3R)-2-Amino-3-hydroxy-4-(4-methoxyphenyl)butanoic acid 在 吡啶 、 sodium hydroxide 、 4-溴苯磺酰氯 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.33h， 生成 (3S,4R)-3-<<(2-Nitrophenyl)sulfenyl>amino>-4-<(4-methoxyphenyl)methyl>-2-oxetanone
  参考文献：
  名称：

  Synthesis, Stability, and Antimicrobial Activity of (+)-Obafluorin and Related .beta.-Lactone Antibiotics

  摘要：

  Optically pure obafluorin(l), an antibacterial agent from Pseudomonas fluorescens, was synthesized in six steps via lactonization of N-[(2-nitrophenyl)sulfenyl]-(2S,3R)-2-amino-3-hydroxy-4-(4-nitrophenyl)butanoic acid (12a), which was prepared in a stereospecific manner from 4-nitrophenylacetaldehyde (9a) and (S)-1-benzoyl-2-tert-butyl-3-methyl-4-imidazolidinone (7). A series of analogues was then synthesized in order to probe structural features required for antibacterial activity as well as those responsible for the hydrolytic decomposition of 1 to the corresponding hydroxy acid 23a. Analogues 22b and 22e wherein the nitro group of 1 is replaced with hydrogen and chlorine, respectively, were prepared in a fashion similar to 1, as were the N-acetyl, N-benzoyl, and N-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetyl (ATMO) derivatives 24a-c. The tosylate salt of L-threonine-beta-lactone (21) was transformed to a series of N-acylated derivatives including the following: 22d (2,3-dihydroxybenzoyl), 25 (2-hydroxybenzoyl), 27 (3,4-dihydroxybenzoyl), 29 (4'methyl-2,2'-bipyridine-4-carbonyl), 31 (epsilon-(L-alpha-aminoadipoyl)), 34 ((N'-2,3-dihydroxybenzoyl)-beta-alanyl), 35 (bromoacetyl), 36 ((6-purinylthio)acetyl), and 37 ((4-pyridylthio)acetyl). The results show that a-amino beta-lactones bearing an N-acyl group with an o- or p-hydroxybenzoyl moiety are especially prone to decomposition under aqueous conditions and that this effect is enhanced by replacement of the 4-nitrobenzyl group on the oxetanone ring of 1 with a methyl. The N-(3,4-dihydroxybenzoyl)L-threonine beta-lactone (27) converts slowly in the solid state to (4S,5S)-2-(3,4-dihydroxybenzoyl)-5-methyl-2-oxazoline-4-carboxylic acid (39b), which hydrolyzes rapidly in 4:1 CD3CN:D2O to O-(3,4-dihydroxybenzoyl)-L-allothreonine (38b). Direct hydrolysis of 27 to 38b under the same conditions has a half-life of 2.4 days. Preliminary assays for antibacterial activity indicate that 29 has nearly comparable activity to obafluorin(l) but is much more stable. The (2-nitrophenyl)sulfenyl p-lactones 14 and 41, as well as the N-(phenylsulfenyl)-L-threonine beta-lactone (44), are the most active agents in the biological assays.

  DOI：

  10.1021/jo00092a025
• 作为产物：
  描述：

  4-甲氧基苯乙醛 、 (2S)-(+)-1-苯甲酰基-2-叔丁基-3-甲基-4-咪唑啉酮 生成 (2S,3R)-2-Amino-3-hydroxy-4-(4-methoxyphenyl)butanoic acid
  参考文献：
  名称：

  Synthesis, Stability, and Antimicrobial Activity of (+)-Obafluorin and Related .beta.-Lactone Antibiotics

  摘要：

  Optically pure obafluorin(l), an antibacterial agent from Pseudomonas fluorescens, was synthesized in six steps via lactonization of N-[(2-nitrophenyl)sulfenyl]-(2S,3R)-2-amino-3-hydroxy-4-(4-nitrophenyl)butanoic acid (12a), which was prepared in a stereospecific manner from 4-nitrophenylacetaldehyde (9a) and (S)-1-benzoyl-2-tert-butyl-3-methyl-4-imidazolidinone (7). A series of analogues was then synthesized in order to probe structural features required for antibacterial activity as well as those responsible for the hydrolytic decomposition of 1 to the corresponding hydroxy acid 23a. Analogues 22b and 22e wherein the nitro group of 1 is replaced with hydrogen and chlorine, respectively, were prepared in a fashion similar to 1, as were the N-acetyl, N-benzoyl, and N-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetyl (ATMO) derivatives 24a-c. The tosylate salt of L-threonine-beta-lactone (21) was transformed to a series of N-acylated derivatives including the following: 22d (2,3-dihydroxybenzoyl), 25 (2-hydroxybenzoyl), 27 (3,4-dihydroxybenzoyl), 29 (4'methyl-2,2'-bipyridine-4-carbonyl), 31 (epsilon-(L-alpha-aminoadipoyl)), 34 ((N'-2,3-dihydroxybenzoyl)-beta-alanyl), 35 (bromoacetyl), 36 ((6-purinylthio)acetyl), and 37 ((4-pyridylthio)acetyl). The results show that a-amino beta-lactones bearing an N-acyl group with an o- or p-hydroxybenzoyl moiety are especially prone to decomposition under aqueous conditions and that this effect is enhanced by replacement of the 4-nitrobenzyl group on the oxetanone ring of 1 with a methyl. The N-(3,4-dihydroxybenzoyl)L-threonine beta-lactone (27) converts slowly in the solid state to (4S,5S)-2-(3,4-dihydroxybenzoyl)-5-methyl-2-oxazoline-4-carboxylic acid (39b), which hydrolyzes rapidly in 4:1 CD3CN:D2O to O-(3,4-dihydroxybenzoyl)-L-allothreonine (38b). Direct hydrolysis of 27 to 38b under the same conditions has a half-life of 2.4 days. Preliminary assays for antibacterial activity indicate that 29 has nearly comparable activity to obafluorin(l) but is much more stable. The (2-nitrophenyl)sulfenyl p-lactones 14 and 41, as well as the N-(phenylsulfenyl)-L-threonine beta-lactone (44), are the most active agents in the biological assays.

  DOI：

  10.1021/jo00092a025

文献信息

• Efficient Chemoenzymatic Synthesis of α-Aryl Aldehydes as Intermediates in C–C Bond Forming Biocatalytic Cascades
  作者：Anthony Meza、Meghan E. Campbell、Anna Zmich、Sierra A. Thein、Abbigail M. Grieger、Matthew J. McGill、Patrick H. Willoughby、Andrew R. Buller

  DOI：10.1021/acscatal.2c02369

  日期：2022.9.2

  practical routes for the synthesis of complex bioactive molecules. However, the relative sparsity of water-stable carbon electrophiles limits the synthetic complexity of molecules made from such cascades. Here, we develop a chemoenzymatic platform that leverages styrene oxide isomerase (SOI) to convert readily accessible aryl epoxides into α-aryl aldehydes through Meinwald rearrangement. These unstable aldehyde

  多酶生物催化级联正在成为合成复杂生物活性分子的实用途径。然而，水稳性碳亲电子试剂的相对稀少限制了由这种级联制成的分子的合成复杂性。在这里，我们开发了一个化学酶平台，该平台利用氧化苯乙烯异构酶 (SOI) 通过 Meinwald 重排将易于获得的芳基环氧化物转化为 α-芳基醛。然后，这些不稳定的醛中间体被 C-C 键形成酶 ObiH 拦截，ObiH 催化转醛酶与l-苏氨酸的反应，产生具有合成挑战性的 β-羟基-α-氨基酸。两种酶在大肠杆菌中的共表达产生能够合成各种立体纯非标准氨基酸 (nsAA) 的全细胞生物催化剂，并且可以以克规模生产。我们使用同位素标记的底物来探索 SOI 的机制，我们证明它可以催化具有立体特异性 1,2-氢化物转移的协同异构化。通过用最近设计的脱羧醛缩酶拦截它们以产生 γ-羟基 nsAA，进一步确定了原位生成的 α-芳基醛的可行性。总之，这些数据建立了一种在简单的全细胞条件下生产