benzyl 2-(S)-[(tert-butoxycarbonyl)amino]-5-iodopentanoate | 216753-82-1

• 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: benzyl 2-(S)-[(tert-butoxycarbonyl)amino]-5-iodopentanoate
• 英文别名: (S)-2-tert-Butoxycarbonylamino-5-iodopentanoic acid benzyl ester；N-t-butoxycarbonyl-(S)-2-amino-5-iodopentanoic acid benzyl ester；benzyl (2S)-5-iodo-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate
• CAS: 216753-82-1
• 化学式: C₁₇H₂₄INO₄
• 分子量: 433.286
• InChiKey: SPGCBPIDYPGMPJ-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 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：

  benzyl 2-(S)-[(tert-butoxycarbonyl)amino]-5-iodopentanoate 在 三甲基氯硅烷 、 tris(dibenzylideneacetone)dipalladium (0) 、 1,2-二溴乙烷 、 三(邻甲基苯基)磷 、 三氟乙酸 、 锌 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 20.5h， 生成
  参考文献：
  名称：

  Concise Synthesis of Enantiomerically Pure Phenylalanine, Homophenylalanine, and Bishomophenylalanine Derivatives Using Organozinc Chemistry:  NMR Studies of Amino Acid-Derived Organozinc Reagents

  摘要：

  Protected phenylalanines 23 (seven examples), homophenylalanines 7 (eight examples), and bishomophenylalanines 8 (seven examples) have been prepared by palladium-catalyzed coupling of the amino acid-derived organozinc reagents 13, 5, and 6, respectively, with aryl iodides. While the reactions of the zinc reagent 13 may be conducted in both THF and DMF as solvent, the results obtained in DMF are generally superior. In the case of the reagents 5 and 6 the results are far superior in DMF. NMR investigations on the structure of the zinc reagents 13 in THF suggest that there is strong intramolecular coordination of the urethane carbonyl group, whereas in DMF this interaction is completely suppressed.

  DOI：

  10.1021/jo981133u
• 作为产物：
  描述：

  N-叔丁氧羰基-L-谷氨酸 1-苄酯 在 N-甲基吗啉 、 咪唑 、 sodium tetrahydroborate 、 碘 、 三苯基膦 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.25h， 生成 benzyl 2-(S)-[(tert-butoxycarbonyl)amino]-5-iodopentanoate
  参考文献：
  名称：

  Novel thiol- and thioether-containing amino acids: cystathionine and homocysteine families

  摘要：

  Natural l-homocysteine and l,l-cystathionine, along with a series of unnatural analogues, have been prepared from l-aspartic and l-glutamic acid. Manipulation of the protected derivatives provided omega-iodoamino acids, which were used in thioalkylation reactions of sulfur nucleophiles, such as the ester of l-cysteine and potassium thioacetate.

  DOI：

  10.1007/s00726-012-1352-5

文献信息

• Direct synthesis of unprotected phenols using palladium-catalysed cross coupling reactions of functionalised organozinc reagents
  作者：Richard F. W. Jackson、Ian Rilatt、P. John Murray

  DOI：10.1039/b311515a

  日期：——

  Palladium-catalysed reaction of unprotected 2-, 3-, and 4-iodophenols with a range of amino acid derived organozinc reagents (not used in excess) gives the expected products in good to excellent yield, demonstrating that carbon-zinc bonds are not protonated by acidic phenols under the conditions of palladium-catalysed coupling reactions.

  钯催化的未保护的2-，3-和4-碘苯酚与一系列氨基酸衍生的有机锌试剂（未过量使用）的反应可提供预期的产物，收率良好至优异，表明碳-锌键未质子化在钯催化的偶联反应条件下被酸性酚类所取代。
• 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）。
• PAR-2 agonist
  申请人：Kowa Company, Ltd.

  公开号：US08133864B2

  公开（公告）日：2012-03-13

  The present invention relates to a pharmaceutical composition for preventing/treating conditions associated with PAR-2. The present invention also relates to a method for preventing/treating the condition using the pharmaceutical composition and use for manufacturing the pharmaceutical composition. The pharmaceutical composition comprises a compound represented by the following general formula (1), salt or solvate thereof and a pharmaceutically acceptable carrier: Ar—CO—AA1—AA2—AA3—AA4—NH—X—Y (1) wherein, Ar represents a phenyl group or an aromatic heterocyclic group optionally having substituent(s): AA1 represents a hydrophobic amino acid: AA2 represents an amino acid absent of substituent(s) having more than two carbon atoms: AA3 represents an amino acid absent of substituent(s) having more than two carbon atoms: AA4 represents a basic amino acid: X represents a straight chain or branched bivalent saturated aliphatic hydrocarbon group having 1 to 6 carbon atoms: Y represents basic substituent(s); straight chain, branched, or cyclic bivalent saturated aliphatic hydrocarbon group having 1 to 6 carbon atoms; or an aromatic hydrocarbon group having 6 to 10 carbon atoms. The compound represented by the general formula (1) has dramatically improved PAR-2 activation potency compared to peptide comprised of 6 amino acids (Tethered receptor agonist peptide: TRAP) in spite of reduction of the number of amino acid.

  本发明涉及一种用于预防/治疗与PAR-2有关的疾病的药物组合物。本发明还涉及一种使用该药物组合物预防/治疗该疾病的方法以及用于制造该药物组合物的用途。该药物组合物包括下列通式（1）所代表的化合物，其盐或溶剂和药学上可接受的载体：Ar-CO-AA1-AA2-AA3-AA4-NH-X-Y（1），其中，Ar代表苯基或芳香杂环基，可选择具有取代基；AA1代表疏水氨基酸；AA2代表没有取代基的含有两个以上碳原子的氨基酸；AA3代表没有取代基的含有两个以上碳原子的氨基酸；AA4代表碱性氨基酸；X代表直链或支链的二价饱和脂肪族羟基烃基，其具有1到6个碳原子；Y代表碱性取代基；直链、支链或环状的二价饱和脂肪族羟基烃基，其具有1到6个碳原子；或具有6到10个碳原子的芳香族羟基烃基。与由6个氨基酸组成的肽（Tethered receptor agonist peptide: TRAP）相比，通式（1）所代表的化合物的PAR-2激活效能显著提高，尽管氨基酸数量减少。
• 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）。
• Efficient synthesis of benzyl 2-(S)-[(tert-butoxycarbonyl)amino]-ω-iodoalkanoates
  作者：Yohei Koseki、Haruka Yamada、Toyonobu Usuki

  DOI：10.1016/j.tetasy.2011.03.002

  日期：2011.3

  The efficient synthesis of four benzyl 2-(S)-[(tert-butoxycarbonyl)amino]-omega-iodoalkanoates benzyl 2-(S)-[(tert-butoxycarbonyl)amino]-3-iodopropanoate, benzyl 2-(S)-[(tert-butoxycarbonyl)amino]-4-iodobutanoate, benzyl 2-(S)-[(tert-butoxycarbonyl)amino]-5-iodopentanoate, benzyl 2-(S)-[(tert-butoxycarbonyl)amino]-6-iodohexanoate) from natural or protected L-amino acids is described. (C) 2011 Elsevier Ltd. All rights reserved.