(S)-2-((R)-2-tert-butoxycarbonylamino-1-hydroxy-propylamino)-propionic acid | 112196-49-3

• 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-((R)-2-tert-butoxycarbonylamino-1-hydroxy-propylamino)-propionic acid
• 英文别名: BOCNH-D-Ala-L-Ala-OH；Boc-D-Ala-Ala-OH；(2S)-2-[(2R)-2-[(tert-butoxycarbonyl)amino]propanamido]propanoic acid；(2S)-2-[[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]propanoic acid
• CAS: 112196-49-3
• 化学式: C₁₁H₂₀N₂O₅
• 分子量: 260.29
• InChiKey: BZNDDHWTEVCBAD-RQJHMYQMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-2-((R)-2-tert-butoxycarbonylamino-1-hydroxy-propylamino)-propionic acid 在 lithium hydroxide 、 叠氮磷酸二苯酯 、 碳酸氢钠 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 143.0h， 生成 (12R,15S,18S,21S)-18-(4-Methoxy-benzyl)-12,15,17,21,23-pentamethyl-2-oxa-11,14,17,20,23-pentaaza-tricyclo[24.2.2.1^3,7]hentriaconta-1(29),3(31),4,6,26(30),27-hexaene-10,13,16,19,22-pentaone
  参考文献：
  名称：

  Studies on the total synthesis of bouvardin and deoxybouvardin: cyclic hexapeptide cyclization studies and preparation of key partial structures

  摘要：

  DOI：

  10.1021/jo00238a005
• 作为产物：
  描述：

  (S)-2-((R)-2-tert-butoxycarbonylamino-1-hydroxy-propylamino)-propionic acid benzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 18.0h， 以100%的产率得到(S)-2-((R)-2-tert-butoxycarbonylamino-1-hydroxy-propylamino)-propionic acid
  参考文献：
  名称：

  Asymmetric transfer hydrogenation using amino acid derivatives; further studies and a mechanistic proposal

  摘要：

  A series of investigations into the use of amino acid derivatives for the asymmetric catalysis of the transfer hydrogenation of ketones are presented. Based on the results observed, a mechanistic suggestion for the origin of the ellantioselective induction is proposed. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.06.004

文献信息

• [EN] BOUVARDIN DERIVATIVES AND THERAPEUTIC USES THEREOF<br/>[FR] DÉRIVÉS DE BOUVARDINE ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：UNIV COLORADO REGENTS

  公开号：WO2013126617A1

  公开（公告）日：2013-08-29

  The present invention is directed at bouvardin analogs arid related compounds for the treatment of disorders including cancer. Provided herein are bouvardin analogs and related compounds, pharmaceutical compositions and kits comprising at least one bouvardin analog or related compound, and methods for treating disorders including cancer. In some aspects the compounds inhibit translation elongation at the ribosome. The compounds are used in combination with radiation therapy or with known chemotherapeutic compositions.

  本发明涉及博瓦尔丁类似物和相关化合物，用于治疗包括癌症在内的多种疾病。本文提供了博瓦尔丁类似物和相关化合物、含有至少一种博瓦尔丁类似物或相关化合物的药物组合物和试剂盒，以及治疗包括癌症在内的疾病的方法。在某些方面，这些化合物抑制核糖体上的翻译延长。这些化合物与放射疗法或已知的化疗药物组合使用。
• Cation-Transporting Peptides: Scaffolds for Functionalized Pores?
  作者：Harekrushna Behera、Venkatachalam Ramkumar、Nandita Madhavan

  DOI：10.1002/chem.201500881

  日期：2015.7.6

  selectivity of pores by incorporating functional groups inside the pore. Readily accessible octapeptides containing (aminomethyl)benzoic acid and alanine are reported here that preferentially transport cations over halides across the lipid bilayer. Ion transport is hypothesized through pores formed by stable assemblies of the peptides. The aromatic ring(s) appear to be proximal to the pore and could be

  选择性地跨膜运输离子的蛋白质孔是自然界最有效的机器之一。这些孔的选择性可用于离子感测和水净化。由于在实际应用中很难以其活性形式重构膜蛋白，因此需要开发能选择性地跨细胞膜转运离子的坚固的合成化合物。可以设想通过在孔内掺入官能团来调节孔的选择性。此处报道了易于获得的包含（氨基甲基）苯甲酸和丙氨酸的八肽，它们优先于卤化物跨脂质双层转运阳离子。假设通过肽的稳定装配形成的孔通过离子运输。
• DIPEPTOID PRODRUGS AND THE USE THEREOF
  申请人：Lerchen Hans-Georg

  公开号：US20110294719A1

  公开（公告）日：2011-12-01

  The present application relates to dipeptide-like prodrug derivatives of 2-amino-6-([2-(4-chlorophenyl)-1,3-oxazol-4-yl]methyl}sulfanyl)-4-(4-[2,3-dihydroxypropyl]oxy}phenyl)pyridine-3,5-dicarbonitrile, processes for their preparation, their use for the treatment and/or prophylaxis of diseases, and their use for the manufacture of medicaments for the treatment and/or prophylaxis of diseases, especially of cardiovascular disorders.

  本申请涉及2-氨基-6-([2-(4-氯苯基)-1,3-噁唑-4-基]甲基}硫基)-4-(4-[2,3-二羟基丙基]氧基}苯基)吡啶-3,5-二羧腙的二肽类前药衍生物，其制备方法，它们用于治疗和/或预防疾病，以及它们用于制造用于治疗和/或预防疾病的药物，特别是心血管疾病。
• Bouvardin derivatives and therapeutic uses thereof
  申请人：The Regents of the University of Colorado, a body corporate

  公开号：US10259846B2

  公开（公告）日：2019-04-16

  The present invention is directed at bouvardin analogs arid related compounds for the treatment of disorders including cancer. Provided herein are bouvardin analogs and related compounds, pharmaceutical compositions and kits comprising at least one bouvardin analog or related compound, and methods for treating disorders including cancer. In some aspects the compounds inhibit translation elongation at the ribosome. The compounds are used in combination with radiation therapy or with known chemotherapeutic compositions.

  本发明针对用于治疗包括癌症在内的疾病的毛花苷类似物和相关化合物。本发明提供了毛花苷类似物和相关化合物、包含至少一种毛花苷类似物或相关化合物的药物组合物和试剂盒，以及治疗包括癌症在内的疾病的方法。在某些方面，这些化合物可抑制核糖体的翻译延伸。这些化合物可与放射治疗或已知的化疗组合物结合使用。
• N-Desmethyl Derivatives of Deoxybouvardin and RA-VII: Synthesis and Evaluation
  作者：Dale L. Boger、Jiacheng Zhou

  DOI：10.1021/ja00133a010

  日期：1995.7

  The synthesis of the complete set of seven N-desmethyl derivatives of RA-VII (8) are described. Thus, the synthesis of the four 14-membered cycloisodityrosine derivatives 21-24 and their coupling with the two tetrapeptides 32 and 33 followed by formation of the 18-membered ring with macrocyclization provided the full set of seven desmethyl derivatives 14-20 of RA-VII (8). The solution phase conformational properties of 8 and 14-20 were examined by 1D and 2D H-1 NMR to reveal the role of N-methylation on the key conformational aspects of the natural agents. In contrast to each of the simple cycloisodityrosine derivatives 21-24 which adopt a single, rigid solution conformation possessing a secondary or tertiary trans amide central to the 14-membered ring, the natural agents including 8 adopt a single predominant solution conformation (83-88%) that corresponds closely to the X-ray structure conformation which possesses an inherently disfavored cis C-30-N-29 tertiary amide central to the 14-membered cycloisodityrosine subunit. Moreover, this cis amide is the predominant conformation (85-95%) observed with N-29-desmethyl RA-VII (14) indicating that even a secondary C-30-N-29 amide adopts this inherently disfavored cis amide stereochemistry. The minor conformation of 8 observed in solution (12-17%) is shown to be derived from a minor cis C-8-N-9 tertiary amide which was not observed with its conversion to a secondary amide. Both N-9-desmethyl RA-VII (15) and N-9,N-29-desmethyl RA-VII (18) adopt exclusively a single solution conformation that corresponds to the major solution conformations of 8 and 14. This conformation contains a characteristic cis C-30-N-29 amide central to a type VI beta-turn and the cycloisodityrosine subunit, a trans C-8-N-9 amide central to a typical type II beta-turn capped with a tight Ala(4)-NH-O=C-Ala(1) hydrogen bond, and a trans C-14-N-15 N-methyl amide. In sharp contrast, removal of the N-15 methyl group within 16, 17, 19, and 20 results in the adoption of solution conformations possessing the inherently favored trans C-30-N-29 amide central to the cycloisodityrosine (14)-membered subunit. Thus, the N-15-methyl group within 8 is responsible for the agents adoption of the disfavored cis C-30-N-29 amide central to the cycloisodityrosine subunit. Importantly, preceding studies have defined the cycloisodityrosine subunit of 8 as the pharmacophore and, in a reversal of the initially assigned roles, revealed that it is the tetrapeptide housed in the 18-membered ring that induces and maintains the rigid, normally inaccessible cis C-30-N-29 amide conformation within the 14-membered cycloisodityrosine subunit. The studies detailed herein reveal that it is the N-15-methyl group that induces this conformational preference for the disfavored cis C-30-N-29 amide and that its removal results in a major conformational change with adoption of the trans C-30-N-29 amide and a loss of biological activity.Thus, the N-15-methyl group is essential for maintenance of the conformational and biological properties of 8; the N-9-methyl group is not essential, and its removal leads to exclusive population of a single biologically active conformation; and the N-29-methyl group once thought essential td the adoption of the C-30-N-29 cis amide is not essential, and its removal does not alter the conformational or biological properties of 8.