(3R)-3-benzyloxycarbonylaminopentanedioic acid tert butyl ester | 83436-45-7

• 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: (3R)-3-benzyloxycarbonylaminopentanedioic acid tert butyl ester
• 英文别名: Z-beta-Glu(OtBu)-OH；(3R)-5-[(2-methylpropan-2-yl)oxy]-5-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid
• CAS: 83436-45-7
• 化学式: C₁₇H₂₃NO₆
• 分子量: 337.373
• InChiKey: ZWLHJIDBOFBLGR-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H312,H315,H319,H332,H335

反应信息

• 作为反应物：
  描述：

  (3R)-3-benzyloxycarbonylaminopentanedioic acid tert butyl ester 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 12.0h， 生成 Boc-Trp-Leu-β-homo-Asp(OBut)-D-Phe-NH2
  参考文献：
  名称：

  Synthesis of gastrin antagonists, analogs of the C-terminal tetrapeptide of gastrin, by introduction of a .beta.-homo residue

  摘要：

  A series of analogues of Boc-Trp-Leu-Asp-Phe-NH2, a potent gastrin agonist, were synthesized by introducing a beta-homo residue in the sequence. These compounds were tested in vivo on acid secretion, in the anesthetized rat, and for their ability to inhibit binding of labeled gastrin to its receptors on gastric mucosal cells. These analogues behaved as gastrin antagonists. The most potent compounds in this series were Boc-Trp-Leu-beta-homo-Asp-NHCH2C6H5 (10) (IC50 = 1 microM, ED50 = 0.2 mg/kg), Boc-Trp-Leu-beta-homo-Asp-NHCH2CH2C6H5 (11) (IC50 = 0.75 microM, ED50 = 0.5 mg/kg), Boc-Trp-Leu-beta-homo-Asp-Phe-NH2 (12) (IC50 = 1.5 microM, ED50 = 0.1 mg/kg), and Boc-Trp-Leu-beta-homo-Asp-D-Phe-NH2 (13) (IC50 = 2 microM, ED50 = 0.1 mg/kg). We could demonstrate the importance of the region of the peptide bond between leucine and aspartic acid and of the structure of the C-terminal dipeptide Asp-Phe-NH2, for exhibiting biological activity on acid secretion.

  DOI：

  10.1021/jm00123a003
• 作为产物：
  描述：

  N-苄氧羰基-L-天门冬氨酸 4-叔丁酯 在 N-甲基吗啉 、 sodium hydroxide 、 silver benzoate 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 甲醇 为溶剂， 反应 30.92h， 生成 (3R)-3-benzyloxycarbonylaminopentanedioic acid tert butyl ester
  参考文献：
  名称：

  Synthesis of gastrin antagonists, analogs of the C-terminal tetrapeptide of gastrin, by introduction of a .beta.-homo residue

  摘要：

  A series of analogues of Boc-Trp-Leu-Asp-Phe-NH2, a potent gastrin agonist, were synthesized by introducing a beta-homo residue in the sequence. These compounds were tested in vivo on acid secretion, in the anesthetized rat, and for their ability to inhibit binding of labeled gastrin to its receptors on gastric mucosal cells. These analogues behaved as gastrin antagonists. The most potent compounds in this series were Boc-Trp-Leu-beta-homo-Asp-NHCH2C6H5 (10) (IC50 = 1 microM, ED50 = 0.2 mg/kg), Boc-Trp-Leu-beta-homo-Asp-NHCH2CH2C6H5 (11) (IC50 = 0.75 microM, ED50 = 0.5 mg/kg), Boc-Trp-Leu-beta-homo-Asp-Phe-NH2 (12) (IC50 = 1.5 microM, ED50 = 0.1 mg/kg), and Boc-Trp-Leu-beta-homo-Asp-D-Phe-NH2 (13) (IC50 = 2 microM, ED50 = 0.1 mg/kg). We could demonstrate the importance of the region of the peptide bond between leucine and aspartic acid and of the structure of the C-terminal dipeptide Asp-Phe-NH2, for exhibiting biological activity on acid secretion.

  DOI：

  10.1021/jm00123a003

文献信息

• Synthesis of 4-(methoxyethyl) monobactams by a chemicoenzymatic approach.
  作者：HARUO YAMASHITA、NOBUYOSHI MINAMI、KYOICHI SAKAKIBARA、SUSUMU KOBAYASHI、MASAJI OHNO

  DOI：10.1248/cpb.36.469

  日期：——

  As a key intermediate for the synthesis of monobactam analogues, cis-3-benzyloxycarbonyl-amino-4-(2-hydroxyehtyl)-2-azetidinone was synthesized from (4S)-4-methoxycarbonylmethyl-2-azetidinone, and converted into monobactams having a methoxyethyl group at the C-4 position of the β-lactam ring. Among the compounds synthesized, disodium (3S, 4R)-3[2-(2-aminothiazol-4-yl)-(Z)-2-carboxymethoxyiminoacetamido]-4-(2-methoxyethyl)-2-azetidinone-1-sulfonate showed strong activity against a variety of gram-negative bacteria except Pseudomonas aeruginosa. Furthemore, the 4-methoxyethyl derivatives exhibited excellent stabiliy to β-lactamases, and the syntheses of the corresponding trans isomer and 3α-methoxy derivatives are also described.

  作为合成单环β内酰胺类似物的关键中间体，顺-3-苄氧基羰基氨基-4-(2-羟乙基)-2-氮杂环丁酮是由(4S)-4-甲氧基羰基甲基-2-氮杂环丁酮合成的，并转化为在β-内酰胺环C-4位具有甲氧乙基基团的单环β内酰胺。在合成的化合物中，双钠盐(3S, 4R)-3[2-(2-氨基噻唑-4-基)-(Z)-2-羧基甲氧基亚胺乙酰氨基]-4-(2-甲氧乙基)-2-氮杂环丁酮-1-磺酸盐对多种革兰阴性细菌表现出强活性，除了铜绿假单胞菌。此外，4-甲氧乙基衍生物对β-内酰胺酶显示出优异的稳定性，并且相应的反式异构体和3α-甲氧基衍生物的合成也被描述。
• Synthesis and Configuration Confirmation of the ATHOD Fatty Amino Acid Residue in the Burkholdines
  作者：Toma Kadowaki、Rin Kainuma、Seiya Kato、Hiroyuki Konno

  DOI：10.1021/acs.jnatprod.2c00469

  日期：2022.8.26

  Eight possible diastereomers of the 3-amino-5,6,7-trihydroxy octadecanoic acid (ATHOD) moiety of the burkholdines (Bks) have been synthesized and their configurations assigned. Though the relative configuration of the triol in the ATHOD residue of the Bks was proposed to be anti–anti–anti in the literature, 1H NMR spectra of our synthesized anti–anti–anti ATHOD derivative was inconsistent with that

  已经合成了伯克霍尔定 (Bks) 的 3-氨基-5,6,7-三羟基十八烷酸 (ATHOD) 部分的八种可能的非对映异构体，并分配了它们的构型。虽然在文献中提出 Bks 的 ATHOD 残基中三醇的相对构型是反抗反抗的，但我们合成的反抗反抗的1 H NMR 光谱ATHOD 衍生物与分离的 ATHOD 残基的衍生物不一致，表明文献中对该残基的相对构型的分配是不正确的。然而，通过使用 Kishi 的 NMR 数据库方法将我们的 ATHOD 衍生物的 NMR 数据与配置定义的 2-氨基-4-戊醇样品的 NMR 数据进行比较，我们得出结论 ATHOD 部分的绝对构型为 (3 R ,5 S , 6 R ,7 S )。此外，我们发现存在于 occidiofungins A-D 中的 ATHOD 残基具有与所有 Bks 中相同的构型。
• N- and C-terminal modifications of negamycin
  作者：B Raju、Kathleen Mortell、Sampathkumar Anandan、Hardwin O'Dowd、Hongwu Gao、Marcela Gomez、Corinne Hackbarth、Charlotte Wu、Wen Wang、Zhengyu Yuan、Richard White、Joaquim Trias、Dinesh V Patel

  DOI：10.1016/s0960-894x(03)00393-7

  日期：2003.7

  Negamycin 1 is a bactericidal antibiotic with activity against Gram-negative bacteria, and served as a template in an antibiotic discovery program. An orthogonally protected beta-amino acid derivative 3a was synthesized and used in parallel synthesis of negamycin derivatives on solid support. This advanced intermediate was also used for N- and C-terminal modifications using solution-phase methodologies. The N-terminal modifications have resulted in the identification of active analogues, whereas the C-terminal modifications resulted in complete loss of antibacterial activity. The N-methyl negamycin analogue, 19a, inhibits protein synthesis (IC50 = 2.3 muM), has antibacterial activity (Escherichia coli, MIC = 16 mug/mL), and is efficacious in an E. coli murine septicemia model (ED50 = 16.3 mg/kg). (C) 2003 Elsevier Science Ltd. All rights reserved.
• Stereocontrolled synthesis of (+)-negamycin from an acyclic homoallylamine by 1,3-asymmetric induction
  作者：Yi Fong Wang、Toshio Izawa、Susumu Kobayashi、Masaji Ohno

  DOI：10.1021/ja00387a060

  日期：1982.11
• Peptidyl β-homo-aspartals: Specific inhibitors of interleukin-1β converting enzyme and its homologues (caspases)
  作者：Sándor Bajusz、Irén Fauszt、Klára Németh、Éva Barabás、Attila Juhász、Miklós Patthy

  DOI：10.1016/s0960-894x(98)00244-3

  日期：1998.6

  Inhibition of interleukin-1 beta converting enzyme (ICE), apopain, papain, thrombin and trypsin with substrate like peptidyl L- and D-alpha-aldehydes and their L-beta-homo-aldehyde analogues was investigated. The L-beta-homo-aspartals appear to be specific inhibitors for ICE and its homologues; the other enzymes were not inhibited with such L-beta-homo aldehydes. Papain shows tolerance for D-residues at P-1 depending on their chiral stability. (C) 1998 Elsevier Science Ltd. All rights reserved.