N-(N-fluorenylmethyloxycarbonyl-L-leucyl)-4R-hydroxy-L-proline methyl ester

• 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: N-(N-fluorenylmethyloxycarbonyl-L-leucyl)-4R-hydroxy-L-proline methyl ester
• 英文别名: Fmoc-Leu-Hyp-OMe；methyl (2S,4R)-1-[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-methylpentanoyl]-4-hydroxypyrrolidine-2-carboxylate
• 化学式: C₂₇H₃₂N₂O₆
• 分子量: 480.561
• InChiKey: CVQBVPMPEQUCJJ-CQLNOVPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(N-fluorenylmethyloxycarbonyl-L-leucyl)-4R-hydroxy-L-proline methyl ester 在 碘 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 、 mineral oil 为溶剂， 反应 5.33h， 生成 dimethyl N-acetoxymethyl-N-(N-fluorenylmethyloxycarbonyl-L-leucyl)-N-acetoxymethyl-4,5-dehydro-L-homoglutamate
  参考文献：
  名称：

  Domino Process Achieves Site-Selective Peptide Modification with High Optical Purity. Applications to Chain Diversification and Peptide Ligation

  摘要：

  The development of peptide libraries by site-selective modification of a few parent peptides would save valuable time and materials in discovery processes but still is a difficult synthetic challenge. Herein, we introduce natural hydroxyproline as a convertible unit for the production of a variety of optically pure amino acids, including expensive N-alkyl amino acids, homoserine lactones, and Agl lactams, and to achieve the mild, efficient, and site-selective modification of peptides. A domino process is used to cleave the customizable Hyp unit under mild, metal-free conditions. Both terminal and internal positions can be modified, and similar customizable units can be differentiated. The resulting products possess two reactive chains which can be manipulated independently. The versatility and scope of this process is highlighted by its application to the ligation of two peptide chains, and the generation of peptides with several chains and peptides with conformational restrictions.

  DOI：

  10.1021/acs.joc.5b00932
• 作为产物：
  描述：

  Fmoc-L-亮氨酸 、 反式-4-羟基-L-脯氨酸甲酯盐酸盐 在 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 以81%的产率得到N-(N-fluorenylmethyloxycarbonyl-L-leucyl)-4R-hydroxy-L-proline methyl ester
  参考文献：
  名称：

  Creating Diversity by Site-Selective Peptide Modification: A Customizable Unit Affords Amino Acids with High Optical Purity

  摘要：

  The development of peptide libraries by site-selective modification of a few parent peptides would save valuable time and materials in discovery processes, but still is a difficult synthetic challenge. Herein natural hydroxyproline is introduced as a "convertible" unit for the production of a variety of optically pure amino acids, including expensive N-alkyl amino acids, and to achieve the mild, efficient, and site-selective modification of peptides.

  DOI：

  10.1021/ol402800a

文献信息

• METHOD FOR MODIFYING DERIVATIVES OF AMINO ACIDS AND PEPTIDES, COMPOUNDS PRODUCED, AND USE
  申请人：Consejo Superior De Investigaciones Científicas (CSIC)

  公开号：EP2957555A1

  公开（公告）日：2015-12-23

  The invention relates to a novel method for modifying hydroxylated cyclic amino acids, especially 4-hydroxyproline, which is a commercial, relatively cheap, natural amino acid, in order to provide other amino acids of high optical purity. The initial step of the process is a free-radical excision, and the excision product converts itself into non-proteinogenic amino acids by means of reactions such as reduction, reductive amination, and Horner-Wadsworth-Emmons reactions. The method is characterised in that it is applicable to the selective modification of peptides. The invention also relates to the products of said method, such as amino acids that are N-alkylated and/or have side chains with groups of amino, hydroxyl, alkenyl etc., and to the peptidic derivatives thereof of interest as pharmaceuticals, catalysts, molecular imaging probes etc.

  本发明涉及一种新方法，用于修饰羟基环状氨基酸，特别是 4-羟基脯氨酸，这是一种商品化的、相对廉价的天然氨基酸，以提供其他高光学纯度的氨基酸。该工艺的第一步是自由基切除，切除产物通过还原、还原胺化和 Horner-Wadsworth-Emmons 反应等反应转化为非蛋白源氨基酸。该方法的特点是适用于肽的选择性修饰。本发明还涉及上述方法的产物，如经过 N-烷基化和/或具有氨基、羟基、烯基等基团侧链的氨基酸，以及作为药物、催化剂、分子成像探针等的肽衍生物。
• EP2957555
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] METHOD FOR MODIFYING DERIVATIVES OF AMINO ACIDS AND PEPTIDES, COMPOUNDS PRODUCED, AND USE<br/>[ES] PROCEDIMIENTO DE MODIFICACIÓN DE DERIVADOS DE AMINOÁCIDOS Y PÉPTIDOS, COMPUESTOS OBTENIDOS Y UTILIZACIÓN<br/>[FR] PROCÉDÉ DE MODIFICATION DE DÉRIVÉS D'ACIDES AMINÉS ET DE PEPTIDES, COMPOSÉS OBTENUS ET UTILISATION CORRESPONDANTE
  申请人：CONSEJO SUPERIOR INVESTIGACION

  公开号：WO2014125145A1

  公开（公告）日：2014-08-21

  La presente invención describe un nuevo procedimiento para la modificación de amino ácidos cíclicos hidroxilados, particularmente la 4-hidroxiprolina, que es un amino ácido natural, comercial y relativamente barato, para dar otros amino ácidos de alta pureza óptica. El paso inicial del proceso es una escisión radicalaria, y el producto de escisión se convierte en amino ácidos no proteinogénicos usando reacciones como por ejemplo la reducción, la aminación reductiva, y la Horner-Wadsworth-Emmons. Es de destacar la aplicación del procedimiento a la modificación selectiva de péptidos. También se describen los productos de dicho procedimiento, como amino ácidos N-alquilados y/o con cadenas laterales con grupos amino, hidroxilo, alquenilo, etc. y sus derivados peptídicos, de interés como fármacos, catalizadores, sondas para imagen molecular, etc.
• Domino Process Achieves Site-Selective Peptide Modification with High Optical Purity. Applications to Chain Diversification and Peptide Ligation
  作者：Ivan Romero-Estudillo、Alicia Boto

  DOI：10.1021/acs.joc.5b00932

  日期：2015.10.2

  The development of peptide libraries by site-selective modification of a few parent peptides would save valuable time and materials in discovery processes but still is a difficult synthetic challenge. Herein, we introduce natural hydroxyproline as a convertible unit for the production of a variety of optically pure amino acids, including expensive N-alkyl amino acids, homoserine lactones, and Agl lactams, and to achieve the mild, efficient, and site-selective modification of peptides. A domino process is used to cleave the customizable Hyp unit under mild, metal-free conditions. Both terminal and internal positions can be modified, and similar customizable units can be differentiated. The resulting products possess two reactive chains which can be manipulated independently. The versatility and scope of this process is highlighted by its application to the ligation of two peptide chains, and the generation of peptides with several chains and peptides with conformational restrictions.
• Creating Diversity by Site-Selective Peptide Modification: A Customizable Unit Affords Amino Acids with High Optical Purity
  作者：Ivan Romero-Estudillo、Alicia Boto

  DOI：10.1021/ol402800a

  日期：2013.11.15

  The development of peptide libraries by site-selective modification of a few parent peptides would save valuable time and materials in discovery processes, but still is a difficult synthetic challenge. Herein natural hydroxyproline is introduced as a "convertible" unit for the production of a variety of optically pure amino acids, including expensive N-alkyl amino acids, and to achieve the mild, efficient, and site-selective modification of peptides.