(R)-methyl 2-[N-(benzyloxycarbonyl)amino]-4-pentenoate | 127515-28-0

• 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: (R)-methyl 2-[N-(benzyloxycarbonyl)amino]-4-pentenoate
• 英文别名: methyl (R)-N-(benzyloxycarbonyl)-2-amino-4-pentenoate；N-benzyloxycarbonyl-D-allylglycine, methyl ester；methyl (2R)-2-{[(benzyloxy)carbonyl]amino}pent-4-enoate；methyl (2R)-2-(phenylmethoxycarbonylamino)pent-4-enoate
• CAS: 127515-28-0
• 化学式: C₁₄H₁₇NO₄
• 分子量: 263.293
• InChiKey: RKNNPGXXWNQYKS-GFCCVEGCSA-N

物化性质

• 沸点：
  386.7±42.0 °C(Predicted)
• 密度：
  1.132±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-methyl 2-[N-(benzyloxycarbonyl)amino]-4-pentenoate 在 甲酸 、 甲基叔丁基醚 、 palladium 10% on activated carbon 、 chirazyme L₉ (Mucormiehei, Roche) 、 氢气 作用下， 以 aq. phosphate buffer 、 乙酸乙酯 为溶剂， 20.0~25.0 ℃ 、200.0 kPa 条件下， 反应 168.0h， 生成 (2R,4S)-N-BOC-4-羟基哌啶-2-甲酸甲酯
  参考文献：
  名称：

  Chemoenzymatic Synthesis of the Four Diastereoisomers of 4-Hydroxypipecolic Acid from N-Acetyl-(R,S)-allylglycine:  Chiral Scaffolds for Drug Discovery

  摘要：

  All four diastereoisomers of 4-hydroxypipecolic acid were prepared in a form conveniently protected for drug discovery applications with the use of industrially scaleable methodology. Resolution of the racemic starting material using proprietary acylases followed by an acyliminium ion cyclisation gave diastereomeric mixtures of 4-formyloxypipecolic acid, which were differentiated using an enzyme-catalysed hydrolysis. The products were separated, by partition, and by following a sequence of straightforward chemical steps, the individual stereoisomers of the protected 4-hydroxypipecolates were crystallized to optical purity in 100 g quantities.

  DOI：

  10.1021/op020017x
• 作为产物：
  描述：

  D-烯丙基甘氨酸 在 氯化亚砜 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 (R)-methyl 2-[N-(benzyloxycarbonyl)amino]-4-pentenoate
  参考文献：
  名称：

  针对细菌核糖体的沸腾糖苷抗生素的合理设计。

  摘要：

  天然氨基糖苷类抗生素对RNA的识别取决于2-deoxystreptamine（2-DOS）支架，该支架与核糖体解码位点的靶标形成特定的氢键。三维结构信息已用于设计氮杂单糖苷，这是新型抗生素的组成部分，其中2-DOS被杂环支架取代。阿斯庚烷-糖苷在低微摩尔范围内显示出靶标结合和翻译抑制作用，并抑制了金黄色葡萄球菌的生长，包括对氨基糖苷类耐药的菌株。

  DOI：

  10.1016/j.bmcl.2003.11.028

文献信息

• Use of hydrolases for the synthesis of cyclic amino acids
  作者：Richard C Lloyd、Michael C Lloyd、Mark E.B Smith、Karen E Holt、Jonathan P Swift、Philip A Keene、Stephen J.C Taylor、Raymond McCague

  DOI：10.1016/j.tet.2003.10.116

  日期：2004.1

  The synthesis of several cyclic amino acids that have all the necessary structural features to make them ideal scaffolds for use in medicinal chemistry is described. A key step in each synthesis is the use of hydrolase enzymes to define a chiral centre. In order to elaborate these building blocks into more complex molecules, crystallization and asymmetric hydrogenation were used to define further stereocentres

  描述了具有所有必要结构特征以使其成为用于药物化学的理想支架的几种环状氨基酸的合成。每个合成过程中的关键步骤是使用水解酶来定义手性中心。为了将这些结构单元详细化为更复杂的分子，使用了结晶和不对称氢化来定义进一步的立体中心。
• Zn-Catalyzed Asymmetric Allylation for the Synthesis of Optically Active Allylglycine Derivatives. Regio- and Stereoselective Formal α-Addition of Allylboronates to Hydrazono Esters
  作者：Mari Fujita、Takashi Nagano、Uwe Schneider、Tomoaki Hamada、Chikako Ogawa、Shū Kobayashi

  DOI：10.1021/ja710627x

  日期：2008.3.1

  have developed Zn-catalyzed asymmetric allylation of hydrazono esters with allylboronates. The reactions proceeded smoothly in high yields and high stereoselectivities. Remarkably, formal α-addition occurred for α-substituted allylboronates exclusively, and excellent stereoselectivities were observed. This is the first example of catalytic regio- and stereoselective allylations with formal α-addition.

  我们开发了锌催化的腙酯与烯丙基硼酸酯的不对称烯丙基化反应。反应以高产率和高立体选择性顺利进行。值得注意的是，α-取代的烯丙基硼酸酯仅发生了正式的 α-加成，并且观察到了优异的立体选择性。这是具有正式α-加成的催化区域和立体选择性烯丙基化的第一个例子。此外，反应是在水性介质中进行的，水的使用是必不可少的。Zn(OH)2 可能是这种不对称烯丙基化反应的催化剂，并且证实了 Zn(OH)2 的催化活性。这也是手性金属氢氧化物催化不对称反应的首例。
• Resolution of non-proteinogenic amino acids via microbial lipase-catalyzed enantioselective transesterification
  作者：Toshifumi Miyazawa、Motoe Mio、Yuko Watanabe、Takashi Yamada

  DOI：10.1139/v07-154

  日期：2008.3.1

  A number of non-proteinogenic amino acids bearing aliphatic side chains were resolved with moderate to good enantioselectivities (E = 15–42) through the Burkholderia cepacia lipase-catalyzed enantioselective transesterification of the 2,2,2-trifluoroethyl esters of their N-benzyloxycarbonyl derivatives with methanol as a nucleophile in diisopropyl ether.Key words: non-proteinogenic amino acids, microbial lipases, Burkholderia cepacia lipase, 2,2,2-trifluoroethyl ester, enantioselective transesterification, enantioselectivity.

  通过伯克霍尔德氏菌脂肪酶催化的2,2,2-三氟乙基酯的对映体选择性酯化反应，在二异丙基醚中以甲醇为亲核体，分离出了一些带有脂肪族侧链的非蛋白源氨基酸，其对映体选择性为中等到良好（E = 15-42）。关键词：非蛋白源氨基酸；微生物脂肪酶；伯克霍尔德氏菌脂肪酶；2,2,2-三氟乙基酯；对映选择性酯交换反应；对映选择性。
• Synthesis and biological evaluation of cyclopropyl analogs of 2-amino-5-phosphonopentanoic acid
  作者：Michael S. Dappen、Roberto Pellicciari、Benedetto Natalini、Joseph B. Monahan、Claudio Chiorri、Alex A. Cordi

  DOI：10.1021/jm00105a024

  日期：1991.1

  A series of cyclopropyl analogues related to 2-amino-5-phosphonopentanoic acid (AP5) were synthesized and their biological activity was assessed as competitive antagonists for the N-methyl-D-aspartate (NMDA) receptor. In vitro receptor binding using [H-3]-L-glutamate as the radioligand provided affinity data, while modulation of [H-3]MK-801 binding was used as a functional assay. The analogues were also evaluated in [H-3]kainate binding to assess selectivity over non-NMDA glutamate receptors. Of the compounds tested, 4,5-methano-AP5 analogue 26 was the most potent selective NMDA antagonist; however, potency was lower than that for [[(+/-)-2-carboxypiperidin-4-yl]methyl]phosphonic acid (CGS 19755, 5).
• Synthesis of (optically active) sulfur-containing trifunctional amino acids by radical addition to (optically active) unsaturated amino acids
  作者：Quirinus B. Broxterman、Bernard Kaptein、Johan Kamphuis、Hans E. Schoemaker

  DOI：10.1021/jo00049a041

  日期：1992.11

  Sulfur-based radicals, generated from R-S-H-type precursors (R = alkyl, acyl) with AIBN, smoothly add to alpha-allylglycines protected at none, one, or both of the amino acid functions (NH2 and/or CO2H). Sulfur-containing trifunctional amino acids were obtained in good to excellent yields (64-100%). The solvent used for the reaction is critical. Optimal results were obtained when both the unsaturated amino acid and RSH dissolve completely in the medium (dioxane/water or methanol/water are good solvent systems). The scope of the reaction includes alpha-substituted alpha-allylglycine and derivatives as well as beta-substituted beta-allyl-beta-ammo alcohols. In the case of optically active alpha-allylglycine derivatives, radical addition is accompanied by a small amount of racemization, the amount depending on the type of protection and R-S-H. The products are easily optically enriched by crystallization. Addition of sulfur-based radicals to alpha-allylglycine is believed to be an example of a general method for synthesizing optically active trifunctional amino acids from unsaturated amino acids.