ethyl (S)-4-benzyloxycarbonylamino-3-oxo-5-phenylpentanoate | 158744-36-6

• 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: ethyl (S)-4-benzyloxycarbonylamino-3-oxo-5-phenylpentanoate
• 英文别名: Ethyl 4(S)-(benzyloxyformamido)-3-oxo-5-phenylpentanoate；(4S)-4-(N-benzyloxycarbonyl)amino-4-benzyl-3-oxobutanoic acid ethyl ester；ethyl (4S)-3-oxo-5-phenyl-4-(phenylmethoxycarbonylamino)pentanoate
• CAS: 158744-36-6
• 化学式: C₂₁H₂₃NO₅
• 分子量: 369.417
• InChiKey: ZQGXGOOTCYUKTC-SFHVURJKSA-N

物化性质

• 沸点：
  529.2±50.0 °C(Predicted)
• 密度：
  1.184±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl (S)-4-benzyloxycarbonylamino-3-oxo-5-phenylpentanoate 在 palladium on activated charcoal N-乙基吗啉 、 盐酸 、 4-二甲氨基吡啶 、 氢氧化钾 、 sodium hydroxide 、 sodium tetrahydroborate 、 草酰氯 、 三氯溴甲烷 、 氢气 、 2-mercaptopyridine-1-oxide sodium salt 、 对甲苯磺酸 、 溶剂黄146 、 1-羟基苯并三唑一水物 、 N,N-二甲基甲酰胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 异丙醇 、 甲苯 为溶剂， 反应 158.0h， 生成 沙喹那韦
  参考文献：
  名称：

  Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959

  摘要：

  Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials. Six approaches for the large-scale synthesis of this compound have been studied. All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5. They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation. The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1. Kilogram quantities of Ro 31-8959 have been prepared using this route.

  DOI：

  10.1021/jo00092a026
• 作为产物：
  描述：

  N-(苄氧羰基)-L-苯丙氨酸甲酯 、 乙酸乙酯 在 lithium diisopropyl amide 作用下， 生成 ethyl (S)-4-benzyloxycarbonylamino-3-oxo-5-phenylpentanoate
  参考文献：
  名称：

  用于肽模拟约束支架合成的新的基于吡咯的氨基酸

  摘要：

  通过微波辅助Paal-Knorr反应衍生自具有功能同源性的相应β-酮酸酯的1-4个酮酸酯，已经制备了一个新的基于吡咯的氨基酸家族。羧基位于吡咯的3位，而受Cbz部分保护的氨基位于1或2位的侧链上。这些化合物用于制备受限的寡肽。

  DOI：

  10.1016/j.tetlet.2005.07.155

文献信息

• Synthesis of N-protected γ-amino-β-keto-esters from urethane N-carboxyanhydrides (UNCAs)
  作者：Marielle Paris、Jean-Alain Fehrentz、Annie Heitz、Albert Loffet、Jean Martinez

  DOI：10.1016/0040-4039(96)01973-9

  日期：1996.11

  N-protected γ-amino-β-keto-esters were synthesized from the corresponding N-protected N-carboxyanhydride (UNCAs) by reaction with the lithium enolate of ethyl acetate in good yields. These compounds are precursors of statine derivatives.

  通过与乙酸乙酯的烯醇锂反应，由相应的N-保护的N-羧基酸酐（UNCA）合成N-保护的γ-氨基-β-酮酸酯。这些化合物是他汀类衍生物的前体。
• New transient receptor potential TRPV1, TRPM8 and TRPA1 channel antagonists from a single linear β,γ-diamino ester scaffold
  作者：Paula Pérez-Faginas、M. Teresa Aranda、Roberto de la Torre-Martínez、Susana Quirce、Asia Fernández-Carvajal、Antonio Ferrer-Montiel、Rosario González-Muñiz

  DOI：10.1039/c5ra25709c

  日期：——

  screening campaign identified nine β,γ-diamino ester derivatives as TRP modulators. A discrete library of new derivatives (23 components) was prepared in a one-pot two step reductive amination reaction, and evaluated for their ability to block the agonist-induced calcium influx in cells expressing human TRPV1, TRPM8 and TRPA1 channels. Selective antagonists for each channel, as well as dual TRPV1/TRPM8

  高通量筛选活动确定了九种β，γ-二氨基酯衍生物作为TRP调节剂。在一锅两步还原胺化反应中制备了新衍生物（23个组分）的离散库，并评估了它们在表达人TRPV1，TRPM8和TRPA1通道的细胞中阻断激动剂诱导的钙内流的能力。在对该线性支架进行细微修饰之后，可获得每个通道的选择性拮抗剂以及双重TRPV1 / TRPM8和TRPM8 / TRPA1配体。SAR研究揭示了选择性阻断正在研究的三个TRP通道的优选取代基。最有效的TRPV1拮抗剂显示出亚微摩尔IC 50值。
• Process for producing 3-amino-2-oxo-1-halogenopropane derivatives
  申请人：Ajinomoto Co., Inc.

  公开号：EP0774453A1

  公开（公告）日：1997-05-21

  A process for producing a 3-amino-2-oxo-1-halogenopropane derivative is provided. A compound formed by reacting a protected amino acid with an alkali metal enolate of an alkyl acetate is reacted with a halogenating agent for halogenation of the 2-position, or a protected amino acid is reacted with an alkali metal enolate of an alkyl halogenoacetate to form a 4-amino-3-oxo-2-halogenobutanoic acid ester derivative, and hydrolysis and decarboxylation are conducted to produce a 3-amino-2-oxo-1-halogenopropane derivative or its salt. This can then be converted to a 3-amino-1,2-epoxypropane.

  本发明提供了一种生产 3-氨基-2-氧代-1-卤代丙烷衍生物的工艺。将受保护氨基酸与乙酸烷基酯的碱金属烯醇盐反应生成的化合物与卤化剂反应，对 2-位进行卤化，或将受保护氨基酸与卤代乙酸烷基酯的碱金属烯醇盐反应生成 4-氨基-3-氧代-2-卤代丁酸酯衍生物，然后进行水解和脱羧反应，生成 3-氨基-2-氧代-1-卤代丙烷衍生物或其盐。然后再将其转化为 3-氨基-1,2-环氧丙烷。
• Process for producing 4-amino-3-oxo-butanoic acid ester
  申请人：Ajinomoto Co., Inc.

  公开号：EP1097919A2

  公开（公告）日：2001-05-09

  A process for producing a 4-amino-3-oxo-butanoic acid ester of formula (II) is provided. A compound of formula (I) is reacted with an alkali metal enolate of an acetate. The compound of formula II can be used in production of 3-amino-2-oxo-1 halogenopropane derivatives or salts which can be converted to 3-amino-1,2-epxoypropane derivates. wherein Rs represents hydrogen, an optionally substituted alkyl group having from 1 to 10 carbon atoms, an optionally substituted aryl group having from 6 to 15 carbon atoms, an optionally substituted aralkyl group having from 7 to 20 carbon atoms, or the above-mentioned groups containing a hetero atom in the carbon skeleton, P1 and P2, independently from each other, represent hydrogen or an amino-protecting group, or P1 and P2 together form a difunctional amino-protecting group, and R1 represents an optionally substituted alkyl group having from 1 to 10 carbon atoms, an optionally substituted aryl group having from 6 to 15 carbon atoms, an optionally substituted aralkyl group having from 7 to 20 carbon atoms, a trialkylsilyl group having from 4 to 10 carbon atoms, a phenyldialkylsilyl group having 8 to 10 carbon atoms or a diphenylalkylsilyl group having 13 to 15 carbon atoms, wherein Rs, P1 and P2 are as defined above, and E1 represents, as an active carboxy terminal, an ester residue of alkoxy having from 1 to 10 carbon atoms, a phenoxy or benzyloxy group which may have a substituent in the ring.

  本发明提供了一种生产式（II）的 4-氨基-3-氧代丁酸酯的工艺。式（I）化合物与乙酸酯的碱金属烯醇盐反应。式 II 的化合物可用于生产 3-氨基-2-氧代-1-卤代丙烷衍生物或可转化为 3-氨基-1,2-环氧丙烷衍生物的盐类。 其中 Rs 代表氢、具有 1 至 10 个碳原子的任选取代的烷基、具有 6 至 15 个碳原子的任选取代的芳基、具有 7 至 20 个碳原子的任选取代的芳烷基或在碳骨架中含有一个杂原子的上述基团、 P1 和 P2 各自代表氢或氨基保护基团，或 P1 和 P2 共同组成双官能氨基保护基团，以及 R1 代表具有 1 至 10 个碳原子的任选取代的烷基、具有 6 至 15 个碳原子的任选取代的芳基、具有 7 至 20 个碳原子的任选取代的芳烷基、具有 4 至 10 个碳原子的三烷基硅基、具有 8 至 10 个碳原子的苯基二烷基硅基或具有 13 至 15 个碳原子的二苯基烷基硅基、 其中 Rs、P1 和 P2 如上定义，以及 E1 作为活性羧基末端，代表具有 1 至 10 个碳原子的烷氧基、苯氧基或苄氧基的酯残基，其环上可能有取代基。
• An efficient synthesis of γ-amino β-ketoester by cross-Claisen condensation with α-amino acid derivatives
  作者：Yutaka Honda、Satoshi Katayama、Mitsuhiko Kojima、Takayuki Suzuki、Kunisuke Izawa

  DOI：10.1016/s0040-4039(03)00464-7

  日期：2003.4

  Cross-ester condensation between N-protected amino acid ester and the lithium enolate prepared from alkyl acetate gave the corresponding beta-ketoester in high yield without the formation of the tertiary alcohol that is commonly seen as by-product. This interesting reaction is applicable to the amino acid derivatives with suitable N-protecting groups, which can help to stabilize the reaction intermediates. (C) 2003 Elsevier Science Ltd. All rights reserved.