tert-butyl (3S,αS)-3-(N-benzyl-N-α-methylbenzylamino)butanoate | 161010-97-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl (3S,αS)-3-(N-benzyl-N-α-methylbenzylamino)butanoate
• 英文别名: tert-Butyl (3S)-3-[benzyl-[(1S)-1-phenylethyl]amino]butanoate
• CAS: 161010-97-5
• 化学式: C₂₃H₃₁NO₂
• 分子量: 353.505
• InChiKey: OAZSEAYAIFYYFG-OALUTQOASA-N

物化性质

• 沸点：
  429.6±33.0 °C(Predicted)
• 密度：
  1.029±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl (3S,αS)-3-(N-benzyl-N-α-methylbenzylamino)butanoate 在 叠氮磷酸二苯酯 、 (1S)-(+)-10-樟脑磺哑嗪 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 59.5h， 生成 tert-butyl (2S,3S,αS)-2-azido-3-(N-benzyl-N-α-methylbenzylamino)butanoate
  参考文献：
  名称：

  Nine Enzymes Are Required for Assembly of the Pacidamycin Group of Peptidyl Nucleoside Antibiotics

  摘要：

  Pacidamycins are a family of uridyl peptide antibiotics that inhibit the translocase MraY, an essential enzyme in bacterial cell wall biosynthesis that to date has not been clinically targeted. The pacidamycin structural skeleton contains a doubly inverted peptidyl chain with a beta-peptide and a ureido linkage as well as a 3'-deoxyuridine nucleoside attached to DABA(3) of the peptidyl chain via an enamide linkage. Although the biosynthetic gene cluster for pacidamycins was identified recently, the assembly line of this group of peptidyl nucleoside antibiotics remained poorly understood because of the highly dissociated nature of the encoded nonribosomal peptide synthetase (NRPS) domains and modules. This work has identified a minimum set of enzymes needed for generation of the pacidamycin scaffold from amino acid and nucleoside monomers, highlighting a freestanding thiolation (T) domain (PacH) as a key carrier component in the peptidyl chain assembly as well as a freestanding condensation (C) domain (PacI) catalyzing the release of the assembled peptide by a nucleoside moiety. On the basis of the substrate promiscuity of this enzymatic assembly line, several pacidamycin analogues were produced using in vitro total biosynthesis.

  DOI：

  10.1021/ja2011109
• 作为产物：
  描述：

  二乙基膦酰基乙酸叔丁酯 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 4.0h， 生成 tert-butyl (3S,αS)-3-(N-benzyl-N-α-methylbenzylamino)butanoate
  参考文献：
  名称：

  平行合成手性β-氨基酸

  摘要：

  使用高手性锂N-苄基-N-（α-甲基苄基）酰胺的共轭加成，完成了对映体纯度高的30个β-氨基酸阵列的平行不对称合成。该协议的实验简单性和高度实用性通过高15种α，β-不饱和酯的高效平行转化为相应β-氨基酸的对映体系列以高总收率和选择性进行了证明，且每个步骤的纯化步骤最少反应方案。

  DOI：

  10.1016/j.tetasy.2007.06.008

文献信息

• Double asymmetric induction as a mechanistic probe: the doubly diastereoselective conjugate addition of enantiopure lithium amides to enantiopure α,β-unsaturated esters and enantiopure α,β-unsaturated hydroxamates
  作者：Stephen G. Davies、James A. Lee、Paul M. Roberts、James E. Thomson、Jingda Yin

  DOI：10.1016/j.tet.2011.05.102

  日期：2011.8

  diastereoselective conjugate addition of the antipodes of lithium N-benzyl-N-(α-methylbenzyl)amide to a range of enantiopure α,β-unsaturated esters [derived from Corey’s 8-phenylmenthol chiral auxiliary] and enantiopure α,β-unsaturated hydroxamates [derived from our ‘chiral Weinreb amide’ auxiliary (S)-N-1-(1′-naphthyl)ethyl-O-tert-butylhydroxylamine] has been used as a mechanistic probe to determine the

  将N-苄基-N-（α-甲基苄基）锂的对映体双非对映选择性共轭加成到一系列对映纯α，β-不饱和酯[源自Corey's 8-苯基薄荷醇手性助剂]和对映纯α，β-不饱和异羟肟酸盐[源自我们的“手性Weinreb酰胺”辅助（小号） - ñ -1-（1'-萘基）乙基- ø -叔-butylhydroxylamine]已被用作一种机械探针，以确定这些受体的活性构象。
• Doubly diastereoselective conjugate addition of enantiopure lithium amides to enantiopure N-enoyl oxazolidin-2-ones: a mechanistic probe
  作者：Stephen G. Davies、Ai M. Fletcher、Gesine J. Hermann、Giovanna Poce、Paul M. Roberts、Andrew D. Smith、Miles J. Sweet、James E. Thomson

  DOI：10.1016/j.tetasy.2010.03.033

  日期：2010.7

  diastereoselective conjugate addition of the antipodes of lithium N-benzyl-N-(α-methylbenzyl)amide to a range of enantiopure N-enoyl oxazolidin-2-ones has been used as a mechanistic probe to determine that the reactive conformation is the anti-s-cis form. The β-amino carbonyl products resulting from these conjugate addition reactions are useful templates for further elaboration into an α,β,α-pseudotripeptide

  N-苄基-N-（α-甲基苄基）酰胺锂的对映体向非对映纯N-烯酰基恶唑烷-2-酮的双非对映选择性共轭加成已被用作机械探针来确定反应构象是抗- š -顺式形式。由这些共轭加成反应得到的β-氨基羰基产物是有用的模板，用于进一步加工成α，β，α-伪三肽。
• IMIDAZOPYRIDINE COMPOUNDS
  申请人：Astellas Pharma Inc.

  公开号：US20140088080A1

  公开（公告）日：2014-03-27

  [Problem] An excellent drug for treating or preventing cardiovascular diseases, based on cGMP production enhancing action due to soluble guanylate cyclase activating action, is provided. [Means for Solution] It was found that imidazopyridine compounds having a carbamoyl group at the 3-position and a substituent bonded at the 8-position via an oxygen atom in an imidazo[1,2-a]pyridine skeleton exhibits a cGMP production enhancing action by a potent soluble guanylate cyclase activating action, and is useful as a drug for treating or preventing various soluble guanylate cyclase-related cardiovascular diseases, thereby completing the present invention.

  提供一种用于治疗或预防心血管疾病的优秀药物，其基于可溶性鸟苷酸环化酶激活作用增强cGMP产生的作用。发现在咪唑吡啶骨架中，3-位具有羰胺基团，8-位通过氧原子与取代基键合的咪唑并[1,2-a]吡啶化合物表现出通过强效可溶性鸟苷酸环化酶激活作用增强cGMP产生的作用，并可用作治疗或预防各种可溶性鸟苷酸环化酶相关心血管疾病的药物，从而完成本发明。
• Homochiral lithium amides for the asymmetric synthesis of β-amino acids
  作者：Stephen G. Davies、Narciso M. Garrido、Dennis Kruchinin、Osamu Ichihara、Luke J. Kotchie、Paul D. Price、Anne J. Price Mortimer、Angela J. Russell、Andrew D. Smith

  DOI：10.1016/j.tetasy.2006.05.008

  日期：2006.7

  Secondary homochiral lithium amides derived from α-methylbenzylamine undergo highly diastereoselective conjugate additions to a range of α,β-unsaturated esters. The corresponding β-amino acids are readily liberated by successive N-debenzylation and ester hydrolysis, furnishing (R)-β-amino butyric acid, (R)-β-amino pentanoic acid, (S)-β-leucine, (R)-β-amino octanoic acid, (S)-β-phenylalanine, (S)-β-tyrosine

  衍生自α-甲基苄胺的仲手性锂酰胺会经历高度非对映选择性的共轭加成反应，形成一系列α，β-不饱和酯。通过连续的N-去苄基化和酯水解，可以轻松释放相应的β-氨基酸，从而提供（R）-β-氨基丁酸，（R）-β-氨基戊酸，（S）-β-亮氨酸，（R） -β-氨基辛酸，（S）-β-苯丙氨酸，（S）-β-酪氨酸甲基醚，（S）-β-酪氨酸盐酸盐和（S）-β-（2-甲氧基苯基）-β-氨基丙酸高产和高ee的酸。该程序在天然产物合成中的应用（R证明了）-β-DOPA和（R）-β-赖氨酸。还描述了简化的一锅反应规程的开发，该规程适用于同级手性β-氨基酯的多克规模合成。
• Evaluating β-amino acids as enantioselective organocatalysts of the Hajos–Parrish–Eder–Sauer–Wiechert reaction
  作者：Stephen G. Davies、Angela J. Russell、Ruth L. Sheppard、Andrew D. Smith、James E. Thomson

  DOI：10.1039/b711171a

  日期：——

  A systematic study of the effect of substitution within the β-amino acid framework indicates that both β2- and β3-amino acids catalyse the Hajos–Parrish–Eder–Sauer–Wiechert reaction with poor to reasonable levels of enantioselectivity. These results led to the evaluation of the conformationally constrained β-amino acid (1R,2S)-cispentacin, which catalyses the Hajos–Parrish–Eder–Sauer–Wiechert reaction with comparable or higher levels of enantioselectivity to L-proline.

  对β-氨基酸框架内取代效应的系统研究表明，β2-和β3-氨基酸催化Hajos–Parrish–Eder–Sauer–Wiechert反应的对映选择性较低至合理。这些结果促使对构象受限的β-氨基酸(1R,2S)-cispentacin进行评估，该氨基酸催化Hajos–Parrish–Eder–Sauer–Wiechert反应的对映选择性与L-脯氨酸相比相当或更高。