benzyl N-[(2S,3R)-3-(N-benzyloxycarbonyl)amino-2-hydroxy-4-phenylbutanoyl]-L-leucinate | 60016-66-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: benzyl N-[(2S,3R)-3-(N-benzyloxycarbonyl)amino-2-hydroxy-4-phenylbutanoyl]-L-leucinate
• 英文别名: (2S,3R)-3-(benzyloxycarbonyl)amino-2-hydroxy-4-phenylbutanoyl-L-leucine benzyl ester；Z-(2S,3R)-AHPA-(S)-Leu-OBzl；Cbz-bAla(2S-OH,3R-Bn)-Leu-OBn；benzyl (2S)-2-[[(2S,3R)-2-hydroxy-4-phenyl-3-(phenylmethoxycarbonylamino)butanoyl]amino]-4-methylpentanoate
• CAS: 60016-66-2
• 化学式: C₃₁H₃₆N₂O₆
• 分子量: 532.637
• InChiKey: NXVWJARYJLMFDA-PKTNWEFCSA-N

物化性质

• 沸点：
  742.4±60.0 °C(Predicted)
• 密度：
  1.194±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  39
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzyl N-[(2S,3R)-3-(N-benzyloxycarbonyl)amino-2-hydroxy-4-phenylbutanoyl]-L-leucinate 在 钯 氢气 作用下， 以 甲醇 、 水 为溶剂， 生成 乌苯美司
  参考文献：
  名称：

  碘代氨基甲酸酯从无环烯丙基胺立体控制合成（-）-贝斯他汀

  摘要：

  通过使用烯丙胺2和6描述了碘代氨基甲酸酯化反应的1,2-不对称诱导作用，该方法已成功地应用于Bestatin的立体控制合成中。

  DOI：

  10.1016/s0040-4039(01)91124-4
• 作为产物：
  描述：

  (2R,3R)-2-hydroxy-3-(benzyloxycarbonylamino)-4-phenylbutanoic acid methyl ester 在 ammonium hydroxide 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 benzyl N-[(2S,3R)-3-(N-benzyloxycarbonyl)amino-2-hydroxy-4-phenylbutanoyl]-L-leucinate
  参考文献：
  名称：

  由L-天冬氨酸新合成（-）-Bestatin。

  摘要：

  可以容易地从L-天冬氨酸获得的恶唑啉-4-乙酸酯衍生物3进行高度立体选择性羟基化，随后羟基的Mitsunobu转化导致（2S，3R）-3-氨基-3-苄基-2-羟基丁酸衍生物8的收率好。8与L-亮氨酸苄基酯的偶联以及随后的保护基的裂解以高收率提供了（-）-贝他汀1。

  DOI：

  10.1271/bbb.63.1304

文献信息

• A New One-Pot Method for the Synthesis of α-Siloxyamides from Aldehydes or Ketones and Its Application to the Synthesis of (−)-Bestatin
  作者：Hisao Nemoto、Rujian Ma、Ichiro Suzuki、Masayuki Shibuya

  DOI：10.1021/ol006816m

  日期：2000.12.1

  A new one-pot method for the synthesis of alpha-siloxyamides is described. The three substrates, H-C(CN)(2)O-SiMe(2)t-Bu, aldehydes or ketones, and primary or secondary amines, are simply mixed in one portion in acetonitrile or ether; the alpha-siloxyamides are obtained within short peroids in excellent yields in many cases. As a demonstration of our method, the synthesis of (-)-bestatin was carried

  描述了一种合成α-甲硅烷氧基酰胺的新的一锅法。将三种底物HC（CN）（2）O-SiMe（2）t-Bu，醛或酮以及伯胺或仲胺简单地在乙腈或乙醚中混合一份；在许多情况下，α-甲硅烷氧基酰胺可在短周期内以优异的收率获得。为了证明我们的方法，进行了（-）-贝斯他汀的合成。
• Process for producing threo-3-amino-2-hydroxybutanoyl-aminoacetic acids,
  申请人：Nippon Kayaku Kabushiki Kaisha

  公开号：US04281180A1

  公开（公告）日：1981-07-28

  A process for producing threo-3-amino-2-hydroxybutanoylaminoacetic acids comprises the steps of allowing to react a starting compound represented by the general formula: ##STR1## wherein R.sub.1 represents a naphthyl or a group of the formula: ##STR2## in which R.sub.6 and R.sub.7 represent individually hydrogen, halogen, amino or a protected amino, hydroxy or a protected hydroxy, a lower alkoxy or a lower alkyl and R.sub.2 represents a protected amino, with a starting compound represented by the general formula: ##STR3## wherein R.sub.3 represents hydrogen or an ester residue, to obtain threo-3-protected amino-2-hydroxy-4-oxobutanoic acid or its ester represented by the general formula: ##STR4## wherein R.sub.1, R.sub.2 and R.sub.3 have the same meanings as above, and then reducing the same into threo-3-protected amino-2-hydroxybutanoic acid or its ester represented by the general formula: ##STR5## wherein R.sub.1, R.sub.2 and R.sub.3 have the same meanings as above, and further converting the above compound into 3-amino-2-hydroxybutanoic acid represented by the general formula: ##STR6## wherein R.sub.2 ' represents amino or a protected amino, thereafter condensing the same, in a conventional manner for forming a peptide coupling, with a compound represented by the general formula: ##STR7## wherein R.sub.4 represents an alkyl having 3-4 carbon atom or 3-guanidinopropyl, while previously protecting as required those groups not relevant to the reaction, and removing the protecting groups for the functional groups to produce threo-3-amino-2-hydroxybutanoylaminoacetic acids represented by the general formula: ##STR8## wherein R.sub.1 and R.sub.4 have the same meanings as above. This invention also provides the compounds represented by the general formula (III) as novel intermediates for the above aimed compounds and a process for producing the intermediates.

  一种制备threo-3-氨基-2-羟基丁酰胺基乙酸的方法，包括以下步骤：将由通式表示的起始化合物反应：##STR1## 其中R.sub.1表示萘基或公式的基团：##STR2## 其中R.sub.6和R.sub.7分别表示氢、卤素、氨基或受保护的氨基、羟基或受保护的羟基、低级烷氧基或低级烷基，R.sub.2表示受保护的氨基，与由通式表示的起始化合物反应：##STR3## 其中R.sub.3表示氢或酯基残基，以获得threo-3-受保护氨基-2-羟基-4-酮丁酸或其由通式表示的酯：##STR4## 其中R.sub.1、R.sub.2和R.sub.3具有与上述相同的含义，然后将其还原为threo-3-受保护氨基-2-羟基丁酸或其由通式表示的酯：##STR5## 其中R.sub.1、R.sub.2和R.sub.3具有与上述相同的含义，进一步将上述化合物转化为由通式表示的3-氨基-2-羟基丁酸：##STR6## 其中R.sub.2'表示氨基或受保护的氨基，然后以传统方式缩合，与由通式表示的化合物：##STR7## 其中R.sub.4表示具有3-4个碳原子的烷基或3-鸟氨基丙基，在必要时先保护与反应无关的那些基团，然后去除功能基团的保护基团，以生成由通式表示的threo-3-氨基-2-羟基丁酰胺基乙酸：##STR8## 其中R.sub.1和R.sub.4具有与上述相同的含义。本发明还提供了由通式（III）表示的上述目标化合物的新中间体化合物和制备中间体化合物的方法。
• Synthesis and structure-activity relations of bestatin analogs, inhibitors of aminopeptidase B
  作者：Rinzo Nishizawa、Tetsushi Saino、Tomohisa Takita、Hiroyuki Suda、Takaaki Aoyagi、Hamao Umezawa

  DOI：10.1021/jm00214a010

  日期：1977.4

  Stereoisomers and analogues of bestatin, [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine, were synthesized and tested for aminopeptidase B and leucine aminopeptidase inhibiting activity. Among the eight stereoisomers, the 2S stereoisomers exhibited strong activity. In a series of compounds in which the L-leucine residue of bestatin was substituted with other amino acids, only the one containing isoleucine showed more activity than bestatin. Norleucine, norvaline, methionine, valine, serine, glutamine, phenylalanine, glutamic acid, proline, and lysine analogues gave, in that order, decreasing activity. Alkyl and phenyl sub stitution for the benzyl group of bestatin decreased the activity markedly. p-Methyl-, p-chloro-, and p-nitrobestatins showed greater activity than bestatin.
• FR2318863
  申请人：——

  公开号：——

  公开（公告）日：——
• UMEZAWA, HAMAO;AOYAGI, TAKAAKI;SHIRAI, TADASHI;NISHIZAWA, RINZO;SUZUKI, M+
  作者：UMEZAWA, HAMAO、AOYAGI, TAKAAKI、SHIRAI, TADASHI、NISHIZAWA, RINZO、SUZUKI, M+

  DOI：——

  日期：——