(S)-2-<(tert-butoxycarbonyl)amino>-6-phenylhexanoic acid | 150722-68-2

• 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: (S)-2-<(tert-butoxycarbonyl)amino>-6-phenylhexanoic acid
• 英文别名: (S)-2-tert-Butoxycarbonylamino-6-phenylhexanoic acid；Boc-(s)-2-amino-6-phenylhexanoic acid；(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-6-phenylhexanoic acid
• CAS: 150722-68-2
• 化学式: C₁₇H₂₅NO₄
• 分子量: 307.39
• InChiKey: FOYWIHNYTBRBBB-AWEZNQCLSA-N

物化性质

• 沸点：
  490.4±45.0 °C(Predicted)
• 密度：
  1.105±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-<(tert-butoxycarbonyl)amino>-6-phenylhexanoic acid 在 N-甲基吗啉 、 sodium hydroxide 、 silver benzoate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 三氟乙酸 、 氯甲酸异丁酯 作用下， 以 甲醇 、 乙二醇二甲醚 、 乙醚 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 6.58h， 生成 Z-(D)-Trp-Nle-(S)-β-homo-Aph-OBzl
  参考文献：
  名称：

  Synthesis and biological evaluation of cholecystokinin analogs in which the Asp-Phe-NH2 moiety has been replaced by a 3-amino-7-phenylheptanoic acid or a 3-amino-6-(phenyloxy)hexanoic acid

  摘要：

  Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester (JMV180), an analog of the C-terminal octapeptide of cholecystokinin (CCK-8), shows interesting biological activities behaving as an agonist at the high-affinity CCK binding sites and as an antagonist at the low-affinity CCK binding sites in rat pancreatic acini. Although we did not observe any major hydrolysis of the ester bond of Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester in our in vitro studies, we were aware of a possible and rapid cleavage of this ester bond during in vivo studies. To improve the stability of Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester, we decided to synthesize analogs in which the ester bond would be replaced by a carba (CH2-CH2) linkage. We synthesized the 3-amino-7-phenylheptanoic acid (beta-homo-Aph) with the R configuration in order to mimic the Asp-2-phenylethyl ester moiety and the 3-amino-6-(phenyloxy)hexanoic acid (H-beta-homo-App-OH), an analog of H-beta-homo-Aph-OH in which a methylene group has been replaced by an oxygen. (R)-beta-Homo-Aph and (R)-H-beta-homo-App-OH were introduced in the CCK-8 sequence to produce Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-(R)-beta-homo-Aph-OH and Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-(R)-beta-homo-App-OH. Both compounds were able to recognize the CCK receptor on rat pancreatic acini (IC50 = 12 +/- 8 nM and 13 +/- 5 nM, respectively), on brain membranes (IC50 = 32 +/- 2 nM and 57 +/- 5 nM, respectively), and on Jurkat T cells (IC50 = 75 +/- 15 nM and 65 +/- 21 nM, respectively). Like Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester, both compounds produced maximal stimulation of amylase secretion (EC50 = 6 +/- 2 nM and 4 +/- 2 nM, respectively) with no decrease of the secretion at high concentration indicating that these compounds probably act as agonists at the high-affinity peripheral CCK-receptor and as antagonists at the low-affinity CCK-receptor. Replacing the tryptophan by a D-tryptophan in such analogs produced full CCK-receptor antagonists. All these analogs might be more suitable for in vivo studies than Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester.

  DOI：

  10.1021/jm00072a024
• 作为产物：
  描述：

  4-苯基-1-丁基溴 在 盐酸 、 sodium hydroxide 、 potassium chloride 、 sodium 作用下， 以 1,4-二氧六环 、 乙醇 、 二甲基亚砜 为溶剂， 反应 18.75h， 生成 (S)-2-<(tert-butoxycarbonyl)amino>-6-phenylhexanoic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of cholecystokinin analogs in which the Asp-Phe-NH2 moiety has been replaced by a 3-amino-7-phenylheptanoic acid or a 3-amino-6-(phenyloxy)hexanoic acid

  摘要：

  Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester (JMV180), an analog of the C-terminal octapeptide of cholecystokinin (CCK-8), shows interesting biological activities behaving as an agonist at the high-affinity CCK binding sites and as an antagonist at the low-affinity CCK binding sites in rat pancreatic acini. Although we did not observe any major hydrolysis of the ester bond of Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester in our in vitro studies, we were aware of a possible and rapid cleavage of this ester bond during in vivo studies. To improve the stability of Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester, we decided to synthesize analogs in which the ester bond would be replaced by a carba (CH2-CH2) linkage. We synthesized the 3-amino-7-phenylheptanoic acid (beta-homo-Aph) with the R configuration in order to mimic the Asp-2-phenylethyl ester moiety and the 3-amino-6-(phenyloxy)hexanoic acid (H-beta-homo-App-OH), an analog of H-beta-homo-Aph-OH in which a methylene group has been replaced by an oxygen. (R)-beta-Homo-Aph and (R)-H-beta-homo-App-OH were introduced in the CCK-8 sequence to produce Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-(R)-beta-homo-Aph-OH and Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-(R)-beta-homo-App-OH. Both compounds were able to recognize the CCK receptor on rat pancreatic acini (IC50 = 12 +/- 8 nM and 13 +/- 5 nM, respectively), on brain membranes (IC50 = 32 +/- 2 nM and 57 +/- 5 nM, respectively), and on Jurkat T cells (IC50 = 75 +/- 15 nM and 65 +/- 21 nM, respectively). Like Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester, both compounds produced maximal stimulation of amylase secretion (EC50 = 6 +/- 2 nM and 4 +/- 2 nM, respectively) with no decrease of the secretion at high concentration indicating that these compounds probably act as agonists at the high-affinity peripheral CCK-receptor and as antagonists at the low-affinity CCK-receptor. Replacing the tryptophan by a D-tryptophan in such analogs produced full CCK-receptor antagonists. All these analogs might be more suitable for in vivo studies than Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester.

  DOI：

  10.1021/jm00072a024

文献信息

• Process for Preparation of Nonnatural Amino Acid and Intermediate Thereof
  申请人：Ishii Yutaka

  公开号：US20070208180A1

  公开（公告）日：2007-09-06

  A process for the preparation of a nonnatural amino acid represented by the following formula (C): which is characterized by reacting a compound represented by the following formula (A1), a compound represented by the following formula (A2) and a compound represented by the following formula (A3) (step 1): to form a compound represented by the following formula (B): and then subjecting the compound (B) to deprotection of protective groups of carboxyl groups and to decarboxylation (wherein X 1 and X 2 are a leaving group, R 1 is an aromatic group, an unsaturated heterocyclic group, or R 6 CO group, R 2 and R 3 are a protected carboxyl group, R 4 is a protected amino group, R 5 is hydrogen atom, an aliphatic hydrocarbon group, an aromatic group, or a heterocyclic group, R 6 is an aromatic group or an unsaturated heterocyclic group, etc., and p, q and r are an integer of 0 to 10).

  一种制备以下式(C)所表示的非天然氨基酸的方法，其特征在于将以下式(A1)、以下式(A2)和以下式(A3)所表示的化合物进行反应（步骤1）：以形成以下式(B)所表示的化合物，然后将化合物(B)进行羧基保护基的去保护和脱羧作用（其中X1和X2是离去基，R1是芳香基、不饱和杂环基或R6CO基，R2和R3是保护羧基，R4是保护氨基，R5是氢原子、脂肪烃基、芳香基或杂环基，R6是芳香基或不饱和杂环基等，p、q和r是0到10的整数）。
• PROCESS FOR PRODUCTION OF NONNATURAL AMINO ACIDS AND INTERMEDIATES THEREFOR
  申请人：DAISO CO., LTD.

  公开号：EP1739077A1

  公开（公告）日：2007-01-03

  A process for the preparation of a nonnatural amino acid represented by the following formula (C): which is characterized by reacting a compound represented by the following formula (A1), a compound represented by the following formula (A2) and a compound represented by the following formula (A3) (step 1): to form a compound represented by the following formula (B): and then subjecting the compound (B) to deprotection of protective groups of carboxyl groups and to decarboxylation (wherein X1 and X2 are a leaving group, R1 is an aromatic group, an unsaturated heterocyclic group, or R6CO group, R2 and R3 are a protected carboxyl group, R4 is a protected amino group, R5 is hydrogen atom, an aliphatic hydrocarbon group, an aromatic group, or a heterocyclic group, R6 is an aromatic group or an unsaturated heterocyclic group, etc., and p, q and r are an integer of 0 to 10).

  一种制备下式(C)所代表的非天然氨基酸的工艺： 其特征在于将下式（A1）代表的化合物、下式（A2）代表的化合物和下式（A3）代表的化合物反应（步骤 1）： 生成下式（B）代表的化合物： 然后将化合物（B）进行羧基保护基团的脱保护和脱羧（其中 X1 和 X2 是离去基团，R1 是芳香基团、不饱和杂环基团或 R6CO 基团，R2 和 R3 是受保护的羧基，R4 是受保护的氨基，R5 是氢原子、脂肪烃基团、芳香基团或杂环基团，R6 是芳香基团或不饱和杂环基团等、以及 p、q 和 r 为 0 至 10 的整数）。
• EP1739077
  申请人：——

  公开号：——

  公开（公告）日：——
• US7750162B2
  申请人：——

  公开号：US7750162B2

  公开（公告）日：2010-07-06
• Synthesis and biological evaluation of cholecystokinin analogs in which the Asp-Phe-NH2 moiety has been replaced by a 3-amino-7-phenylheptanoic acid or a 3-amino-6-(phenyloxy)hexanoic acid
  作者：Muriel Amblard、Marc Rodriguez、Marie Francoise Lignon、Marie Christine Galas、Nicole Bernad、Anne Marie Artis-Noel、Leticia Hauad、Jeanine Laur、Jean Christophe Califano

  DOI：10.1021/jm00072a024

  日期：1993.10

  Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester (JMV180), an analog of the C-terminal octapeptide of cholecystokinin (CCK-8), shows interesting biological activities behaving as an agonist at the high-affinity CCK binding sites and as an antagonist at the low-affinity CCK binding sites in rat pancreatic acini. Although we did not observe any major hydrolysis of the ester bond of Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester in our in vitro studies, we were aware of a possible and rapid cleavage of this ester bond during in vivo studies. To improve the stability of Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester, we decided to synthesize analogs in which the ester bond would be replaced by a carba (CH2-CH2) linkage. We synthesized the 3-amino-7-phenylheptanoic acid (beta-homo-Aph) with the R configuration in order to mimic the Asp-2-phenylethyl ester moiety and the 3-amino-6-(phenyloxy)hexanoic acid (H-beta-homo-App-OH), an analog of H-beta-homo-Aph-OH in which a methylene group has been replaced by an oxygen. (R)-beta-Homo-Aph and (R)-H-beta-homo-App-OH were introduced in the CCK-8 sequence to produce Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-(R)-beta-homo-Aph-OH and Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-(R)-beta-homo-App-OH. Both compounds were able to recognize the CCK receptor on rat pancreatic acini (IC50 = 12 +/- 8 nM and 13 +/- 5 nM, respectively), on brain membranes (IC50 = 32 +/- 2 nM and 57 +/- 5 nM, respectively), and on Jurkat T cells (IC50 = 75 +/- 15 nM and 65 +/- 21 nM, respectively). Like Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester, both compounds produced maximal stimulation of amylase secretion (EC50 = 6 +/- 2 nM and 4 +/- 2 nM, respectively) with no decrease of the secretion at high concentration indicating that these compounds probably act as agonists at the high-affinity peripheral CCK-receptor and as antagonists at the low-affinity CCK-receptor. Replacing the tryptophan by a D-tryptophan in such analogs produced full CCK-receptor antagonists. All these analogs might be more suitable for in vivo studies than Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester.