(S)-2-Amino-hexanedioic acid 6-tert-butyl 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: (S)-2-Amino-hexanedioic acid 6-tert-butyl ester
• 英文别名: (2S)-2-azaniumyl-6-[(2-methylpropan-2-yl)oxy]-6-oxohexanoate
• 化学式: C₁₀H₁₉NO₄
• 分子量: 217.265
• InChiKey: WWSDFHPRIJAESZ-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  89.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-2-Amino-hexanedioic acid 6-tert-butyl ester 在 N-甲基吗啉 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 14.67h， 生成 (S)-5-((2S,3S)-2-Benzyloxycarbonylamino-3-methyl-pentanoylamino)-5-{(S)-1-[(S)-1-((E)-2-methanesulfonyl-vinyl)-3-methyl-butylcarbamoyl]-ethylcarbamoyl}-pentanoic acid tert-butyl ester
  参考文献：
  名称：

  Optimization of Subsite Binding to the β5 Subunit of the Human 20S Proteasome Using Vinyl Sulfones and 2-Keto-1,3,4-oxadiazoles:  Syntheses and Cellular Properties of Potent, Selective Proteasome Inhibitors

  摘要：

  Beginning with the peptide sequence Cbz-Ile-Glu(OtBu)-Ala-Leu found in PSI (3), a series of vinyl sulfones (VS) were synthesized for evaluation as inhibitors of the chymotrypsin-like activity of the 20S proteasome. Variations at the key P3 position confirmed the importance of a long side chain capped with a hydrophobic group for optimal potency, consistent with a model of binding to the S3 subsite. The tert-butyl glutamic ester initially used at P3 gave plasma unstable, insoluble compounds and was replaced with the better isostere, N-beta-neopentyl asparagine. The inhibitors were shortened by replacing the N-terminal Cbz-isoleucine with a p-tosyl group without loss of potency. Small L-amino acids were used at P2, where D-substitution was not tolerated. The resulting optimized P4-P3-P2 sequence was grafted onto a novel proteasome inhibitor warhead, 2-keto-1,3,4-oxadiazoles (KOD), to produce reversible, subnanomolar proteasome inhibitors that were 1000-fold selective versus cathepsin B (CatB), cathepsin S (CatS), and trypsin-like as well as PGPH-like proteasome activity. A number of compounds in both the VS and the KOD series exhibited growth inhibitory effects against the human prostate cancer cell line PC3 at submicromolar concentrations.

  DOI：

  10.1021/jm058289o

文献信息

• A catalytic one-step synthesis of peptide thioacids: the synthesis of leuprorelin <i>via</i> iterative peptide–fragment coupling reactions
  作者：Takuya Matsumoto、Koki Sasamoto、Ryo Hirano、Kounosuke Oisaki、Motomu Kanai

  DOI：10.1039/c8cc07935h

  日期：——

  A catalytic one-step synthesis of peptide thioacids was developed. The oxygen–sulfur atom exchange reaction converted the carboxy group at the C-terminus of the peptides into a thiocarboxy group with suppressed epimerization. This method was successfully applied to the synthesis of the peptide drug leuprorelin via an iterative fragment-coupling protocol.

  开发了一种催化一步合成肽硫代酸的方法。氧-硫原子交换反应将肽C-末端的羧基转化为差向异构化的硫代羧基。该方法已通过迭代片段偶联方案成功应用于肽药物亮丙瑞林的合成。
• Tripeptides of the Type H-D-Pro-Pro-Xaa-NH₂as Catalysts for Asymmetric 1,4-Addition Reactions: Structural Requirements for High Catalytic Efficiency
  作者：Markus Wiesner、Markus Neuburger、Helma Wennemers

  DOI：10.1002/chem.200901021

  日期：2009.10.5

  functional requirements within the asymmetric peptidic catalyst H‐D‐Pro‐Pro‐Asp‐NH2 led to the development of the closely related peptide H‐D‐Pro‐Pro‐Glu‐NH2 as an even more efficient catalyst for asymmetric conjugate addition reactions of aldehydes to nitroolefins. In the presence of as little as 1 mol % of H‐D‐Pro‐Pro‐Glu‐NH2, a broad range of aldehydes and nitroolefins react readily with each other. The resulting

  对不对称肽催化剂H ‐ D ‐Pro‐Pro‐Asp‐NH 2的结构和功能要求的分析导致紧密相关的多肽H ‐ D ‐Pro‐Pro‐Glu‐NH 2的开发醛与硝基烯烃不对称共轭加成反应的催化剂。在低至1 mol％的H ‐ D ‐Pro‐Pro‐Glu‐NH 2存在下，各种各样的醛和硝基烯烃容易相互反应。所得的γ-硝基醛在室温下以优异的收率和立体选择性获得。在肽催化剂的结构内，D‐Pro‐Pro母题是导致高立体选择性的主要因素。C末端酰胺和C末端氨基酸侧链中羧酸的间隔基负责立体选择性的微调。肽催化剂不仅可以在温和的条件下实现高效的不对称催化，而且还可以在没有添加剂的情况下发挥作用。
• RAPAFUCIN DERIVATIVE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：The Johns Hopkins University

  公开号：US20210094933A1

  公开（公告）日：2021-04-01

  The present disclosure provides macrocyclic compounds inspired by the immunophilin ligand family of natural products FK506 and rapamycin. The generation of a Rapafucin library of macrocyles that contain FK506 and rapamycin binding domains should have great potential as new leads for developing drugs to be used for treating diseases.

  本公开提供了受免疫蛋白配体家族FK506和雷帕霉素天然产物启发的大环化合物。生成包含FK506和雷帕霉素结合结构域的Rapafucin大环化合物库，应具有作为治疗疾病新药的潜力。
• Serine protease inhibitors
  申请人：Akzo Nebel

  公开号：US06534495B1

  公开（公告）日：2003-03-18

  The invention relates to a compound having the formula (I): R1SO2—B—X—Z—C(O)—Y, B is a bond, an amino acid of the formula —NR—CH[(CH2)pC(O)OH]—C(O)— or an ester derivative thereof wherein p is 1, 2, or 3, Gly, D-1-Piq, D-3-Piq, D-1-Tiq, D-3-Tiq, D-Atc, Aic, or a L- or D-amino acid having a hydrophobic, basic or neutral side chain; X is an amino acid with a hydrophobic side chain, glutamine, serine, theronine, a cyclic amino acid optionally containing an additional heteroatom selected from N, O or S, and optionally substituted with (1-6C)alkyl, (1-6C)alkoxy, benzyloxy or oxo, or X is 2-amino-isobutyric acid, —NR2—CH2—C(O)— or the fragment (I) or (II), wherein n is 2, 3, or 4, W is CH or N and R3 is H, (1-6C)alkyl or phenyl which groups may optionally be substituted with hydroxy, (1-6C)alkoxy, COOH, COO(1-6C)alkyl, CONH2, or halogen; Z is lysine or 4-aminocyclohexylglycine. The compounds of the invention have anticoagulant activity and can be used in treating or preventing thrombin-related diseases. The variable R1 and Y are defined in claim 1.

  本发明涉及一种具有以下式子（I）的化合物：R1SO2—B—X—Z—C（O）—Y，其中B为键，为式子—NR—CH[(CH2)pC(O)OH]—C(O)—的氨基酸或其酯衍生物，其中p为1、2或3，Gly、D-1-Piq、D-3-Piq、D-1-Tiq、D-3-Tiq、D-Atc、Aic或具有疏水性、碱性或中性侧链的L-或D-氨基酸；X为具有疏水性侧链的氨基酸、谷氨酰胺、丝氨酸、苏氨酸、一个环状氨基酸，可选地含有从N、O或S中选择的额外杂原子，并可选地用(1-6C)烷基、(1-6C)烷氧基、苄氧基或氧代取代，或X为2-氨基异丁酸，—NR2—CH2—C(O)—或片段(I)或(II)，其中n为2、3或4，W为CH或N，R3为H、(1-6C)烷基或苯基，这些基团可以选择性地用羟基、(1-6C)烷氧基、COOH、COO(1-6C)烷基、CONH2或卤素取代；Z为赖氨酸或4-氨基环己基甘氨酸。本发明的化合物具有抗凝血活性，可用于治疗或预防与凝血酶相关的疾病。变量R1和Y在权利要求1中定义。
• Enzymatic encoding methods for efficient synthesis of large libraries
  申请人：Nuevolution A/S

  公开号：EP2341140A1

  公开（公告）日：2011-07-06

  Disclosed is a method for obtaining a bifunctional complex comprising a molecule linked to a single stranded identifier oligonucleotide, wherein a nascent bifunctional complex comprising a chemical reaction site and a priming site for enzymatic addition of a tag is a) reacted at the chemical reaction site with one or more reactants, and b) reacted enzymatically at the priming site with one or more tag(s) identifying the reactant(s).

  本发明公开了一种获得双功能复合物的方法，该复合物由与单链标识寡核苷酸相连的分子组成，其中包含化学反应位点和用于酶加标记的引物位点的新生双功能复合物 a) 在化学反应位点与一种或多种反应物反应，b) 在引物位点与一种或多种标识反应物的标记进行酶反应。