2-(benzyloxycarbonylamino)octanoic acid | 76313-08-1

• 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: 2-(benzyloxycarbonylamino)octanoic acid
• 英文别名: (+/-)-N-(benzyloxycarbonyl)-α-aminooctanoic acid；N-Cbz-aminooctanoic acid；DL-α-Benzyloxycarbonylamino-octansaeure；2-{[(Benzyloxy)carbonyl]amino}octanoic acid；2-(phenylmethoxycarbonylamino)octanoic acid
• CAS: 76313-08-1
• 化学式: C₁₆H₂₃NO₄
• 分子量: 293.363
• InChiKey: PWTXIAIUZAYHGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  2-(benzyloxycarbonylamino)octanoic acid 在 钯 N-甲基吗啉 、 氢气 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 40.0h， 生成 D,L-1-<5'-<(α-aminooctanoyl)amino>-5'-deoxy-β-D-allofuranosyuronic acid>uracil formate
  参考文献：
  名称：

  Synthesis and anticandidal properties of polyoxin L analogs containing .alpha.-amino fatty acids

  摘要：

  Analogues of polyoxin L containing amino acids with saturated fatty acid like side chains were synthesized from the benzyloxycarbonyl-protected alpha-amino fatty acid p-nitrophenyl ester and uracil polyoxin C. Transfer hydrogenolysis using palladium black and formic acid gave diastereomeric, dipeptidyl polyoxin L analogues containing alpha-aminooctanoic acid (3), alpha-aminododecanoic acid (4), or alpha-aminohexadecanoic acid (5) as the amine terminal residue in 40-60% yield. Diastereomers of 3 and 5 were resolved by using high-performance liquid chromatography on a reversed-phase column and designated as 3a, 3b and 5a, 5b. Analogues 3-5 were excellent inhibitors of chitin synthetase from Candida albicans; 4, the best inhibitor, had an ID50 of 0.5 microM. The L,L diastereomers of 3 and 5 were 1-2 orders of magnitude more potent chitin synthetase inhibitors than their D,L homologues. None of the synthetic polyoxin L analogues inhibited transport of trimethionine, but 3a, 4, and 5b caused decreases of 71%, 87%, and 83%, respectively, in the initial rate of uptake of dileucine. Compounds 3-5 were significantly more stable to peptidase degradation than polyoxin L analogues containing naturally occurring alpha-amino acids. Compound 4 inhibited growth of C. albicans in culture at 40-80 micrograms/mL. All other analogues were less potent antifungals. The results suggest that synthetic polyoxins can be designed to have increased affinity for a peptide transport system and to have increased stability against intracellular degradation in C. albicans.

  DOI：

  10.1021/jm00398a027
• 作为产物：
  描述：

  2-溴正辛酸 在 ammonium hydroxide 、 sodium hydroxide 作用下， 反应 171.0h， 生成 2-(benzyloxycarbonylamino)octanoic acid
  参考文献：
  名称：

  Synthesis and anticandidal properties of polyoxin L analogs containing .alpha.-amino fatty acids

  摘要：

  Analogues of polyoxin L containing amino acids with saturated fatty acid like side chains were synthesized from the benzyloxycarbonyl-protected alpha-amino fatty acid p-nitrophenyl ester and uracil polyoxin C. Transfer hydrogenolysis using palladium black and formic acid gave diastereomeric, dipeptidyl polyoxin L analogues containing alpha-aminooctanoic acid (3), alpha-aminododecanoic acid (4), or alpha-aminohexadecanoic acid (5) as the amine terminal residue in 40-60% yield. Diastereomers of 3 and 5 were resolved by using high-performance liquid chromatography on a reversed-phase column and designated as 3a, 3b and 5a, 5b. Analogues 3-5 were excellent inhibitors of chitin synthetase from Candida albicans; 4, the best inhibitor, had an ID50 of 0.5 microM. The L,L diastereomers of 3 and 5 were 1-2 orders of magnitude more potent chitin synthetase inhibitors than their D,L homologues. None of the synthetic polyoxin L analogues inhibited transport of trimethionine, but 3a, 4, and 5b caused decreases of 71%, 87%, and 83%, respectively, in the initial rate of uptake of dileucine. Compounds 3-5 were significantly more stable to peptidase degradation than polyoxin L analogues containing naturally occurring alpha-amino acids. Compound 4 inhibited growth of C. albicans in culture at 40-80 micrograms/mL. All other analogues were less potent antifungals. The results suggest that synthetic polyoxins can be designed to have increased affinity for a peptide transport system and to have increased stability against intracellular degradation in C. albicans.

  DOI：

  10.1021/jm00398a027

文献信息

• Kinetic resolutions of chiral 2-and-3-substituted carboxylic acids
  申请人：——

  公开号：US20020151744A1

  公开（公告）日：2002-10-17

  One aspect of the present invention relates to a method for the kinetic resolution of racemic and diastereomeric mixtures of chiral compounds. The critical elements of the method are: a non-racemic chiral tertiary-amine-containing catalyst; a racemic or diastereomeric mixture of a chiral substrate, e.g., a cyclic carbonate or cyclic carbamate; and a nucleophile, e.g., an alcohol, amine or thiol. A preferred embodiment of the present invention relates to a method for achieving the kinetic resolution of racemic and diastereomeric mixtures of derivatives of &agr;- and &bgr;-amino, hydroxy, and thio carboxylic acids. In certain embodiments, the methods of the present invention achieve dynamic kinetic resolution of a racemic or diastereomeric mixture of a substrate, i.e., a kinetic resolution wherein the yield of the resolved enantiomer or diastereomer, respectively, exceeds the amount present in the original mixture due to the in situ equilibration of the enantiomers or diastereomers under the reaction conditions prior to the resolution step.

  本发明的一个方面涉及一种用于立体化合物的消旋和对映异质混合物的动力学分离的方法。该方法的关键要素包括：非消旋手性三级胺催化剂；手性底物的消旋或对映异构混合物，例如环碳酸酯或环氨基甲酸酯；以及亲核试剂，例如醇、胺或硫醇。本发明的一种优选实施例涉及一种用于实现对α-和β-氨基、羟基和硫代羧酸衍生物的消旋和对映异质混合物的动力学分离的方法。在某些实施例中，本发明的方法实现了底物的动态动力学分离，即消旋或对映异构混合物的动力学分离，在该分离步骤之前，在反应条件下对映异构体的原始混合物中的分离对映异构体的产率分别超过原始混合物中存在的量，因为在分离步骤之前在原位平衡对映异构体。
• Resolution of non-proteinogenic amino acids via microbial lipase-catalyzed enantioselective transesterification
  作者：Toshifumi Miyazawa、Motoe Mio、Yuko Watanabe、Takashi Yamada

  DOI：10.1139/v07-154

  日期：2008.3.1

  A number of non-proteinogenic amino acids bearing aliphatic side chains were resolved with moderate to good enantioselectivities (E = 15–42) through the Burkholderia cepacia lipase-catalyzed enantioselective transesterification of the 2,2,2-trifluoroethyl esters of their N-benzyloxycarbonyl derivatives with methanol as a nucleophile in diisopropyl ether.Key words: non-proteinogenic amino acids, microbial lipases, Burkholderia cepacia lipase, 2,2,2-trifluoroethyl ester, enantioselective transesterification, enantioselectivity.

  通过伯克霍尔德氏菌脂肪酶催化的2,2,2-三氟乙基酯的对映体选择性酯化反应，在二异丙基醚中以甲醇为亲核体，分离出了一些带有脂肪族侧链的非蛋白源氨基酸，其对映体选择性为中等到良好（E = 15-42）。关键词：非蛋白源氨基酸；微生物脂肪酶；伯克霍尔德氏菌脂肪酶；2,2,2-三氟乙基酯；对映选择性酯交换反应；对映选择性。
• [EN] IMMUNITY LINKER MOLECULES AND THEIR USE IN THE TREATMENT OF INFECTIOUS DISEASES<br/>[FR] MOLÉCULES LIEUSES D'IMMUNITÉ ET LEUR UTILISATION DANS LE TRAITEMENT DE MALADIES INFECTIEUSES
  申请人：CENTAURI THERAPEUTICS LTD

  公开号：WO2019175590A1

  公开（公告）日：2019-09-19

  The invention relates to novel compounds with the ability to link an immune response to a pathogen,to the use of said compounds in a disease or disorder mediated and/or caused by an infective agent, to compositions containing said compounds, processes for their preparation and to novel intermediates used in said process.

  本发明涉及具有将免疫反应与病原体联系起来的能力的新化合物，以及在由感染性代理介导和/或导致的疾病或紊乱中使用该化合物，包含该化合物的组合物，其制备过程以及在该过程中使用的新中间体。
• Kinetic resolutions of chiral 2- and 3-substituted carboxylic acids
  申请人：——

  公开号：US20020165393A1

  公开（公告）日：2002-11-07

  One aspect of the present invention relates to a method for the kinetic resolution of racemic and diastereomeric mixtures of chiral compounds. The critical elements of the method are: a non-racemic chiral tertiary-amine-containing catalyst; a racemic or diastereomeric mixture of a chiral substrate, e.g., a cyclic carbonate or cyclic carbamate; and a nucleophile, e.g., an alcohol, amine or thiol. A preferred embodiment of the present invention relates to a method for achieving the kinetic resolution of racemic and diastereomeric mixtures of derivatives of &agr; and &bgr;-amino, hydroxy, and thio carboxylic acids. In certain embodiments, the methods of the present invention achieve dynamic kinetic resolution of a racemic or diastereomeric mixture of a substrate, i.e., a kinetic resolution wherein the yield of the resolved enantiomer or diastereomer, respectively, exceeds the amount present in the original mixture due to the in situ equilibration of the enantiomers or diastereomers under the reaction conditions prior to the resolution step.

  本发明的一个方面涉及手性化合物外消旋体和非对映异构体混合物的动力学解析方法。该方法的关键要素包括：非外消旋手性含叔胺催化剂；手性底物的外消旋或非对映混合物，例如环状碳酸盐或环状氨基甲酸酯；以及亲核剂，例如醇、胺或硫醇。本发明的一个优选实施方案涉及一种实现&agr;和&bgr;-氨基、羟基和硫代羧酸衍生物的外消旋和非对映混合物的动力学解析的方法。在某些实施方案中，本发明的方法实现了底物的外消旋混合物或非对映混合物的动态动力学解析，即动力学解析，由于对映体或非对映异构体在解析步骤之前的反应条件下原位平衡，解析出的对映体或非对映异构体的产率分别超过原始混合物中的产率。
• Kinetic resolutions of chiral 2-and 3-substituted carboxylic acids
  申请人：——

  公开号：US20030166963A1

  公开（公告）日：2003-09-04

  One aspect of the present invention relates to a method for the kinetic resolution of racemic and diastereomeric mixtures of chiral compounds. The critical elements of the method are: a non-racemic chiral tertiary-amine-containing catalyst; a racemic or diastereomeric mixture of a chiral substrate, e.g., a cyclic carbonate or cyclic carbamate; and a nucleophile, e.g., an alcohol, amine or thiol. A preferred embodiment of the present invention relates to a method for achieving the kinetic resolution of racemic and diastereomeric mixtures of derivatives of &agr;- and &bgr;-amino, hydroxy, and thio carboxylic acids. In certain embodiments, the methods of the present invention achieve dynamic kinetic resolution of a racemic or diastereomeric mixture of a substrate, i.e., a kinetic resolution wherein the yield of the resolved enantiomer or diastereomer, respectively, exceeds the amount present in the original mixture due to the in situ equilibration of the enantiomers or diastereomers under the reaction conditions prior to the resolution step.

  本发明的一个方面涉及手性化合物外消旋体和非对映异构体混合物的动力学解析方法。该方法的关键要素包括：非外消旋手性含叔胺催化剂；手性底物的外消旋或非对映混合物，例如环状碳酸盐或环状氨基甲酸酯；以及亲核剂，例如醇、胺或硫醇。本发明的一个优选实施方案涉及一种实现&agr;-和&bgr;-氨基、羟基和硫代羧酸衍生物的外消旋和非对映混合物的动力学解析的方法。在某些实施方案中，本发明的方法实现了底物的外消旋混合物或非对映混合物的动态动力学解析，即动力学解析，解析出的对映体或非对映异构体的产率分别超过原始混合物中的产率，这是由于对映体或非对映异构体在解析步骤之前的反应条件下进行了原位平衡。