(2S)-2-amino-3,3-dimethylpentanoic acid

• 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: (2S)-2-amino-3,3-dimethylpentanoic acid
• 英文别名: 3-methyl-L-alloisoleucine
• 化学式: C₇H₁₅NO₂
• 分子量: 145.202
• InChiKey: AQIFZAKDNFZWND-RXMQYKEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S)-2-amino-3,3-dimethylpentanoic acid 在 盐酸 作用下， 以 水 为溶剂， 生成 (S)-2-amino-3,3-dimethylpentanoic acid hydrochloride
  参考文献：
  名称：

  Diastereoselective Allylstannane Additions to (S)-5,6-Dihydro-2H-5-phenyloxazin-2-one. A Concise Synthesis of (S)-β-Methylisoleucine

  摘要：

  The addition of allyl stannanes to (S)-4,5-dihydro-5-phenyl-2H-oxazinone (3) was achieved under Bronsted acid catalysis to give 2-allylmorpholinones with high diastereoselectivity (up to dr 14.2:1). The product of dimethylallyltributylstannane addition to 3 was converted to L-beta-methylisoleucine, an alpha-amino acid residue found in the complex, biologically active marine-derived peptides polytheonamides A and B, and polydiscamides A-C.

  DOI：

  10.1021/ol1001126
• 作为产物：
  描述：

  2,2-二甲基丁酰氯 在 盐酸 、 lithium aluminium tetrahydride 、 氢气 、 palladium(II) hydroxide 、 溶剂黄146 、 三乙胺 、 zinc(II) iodide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 20.5h， 生成 (2S)-2-amino-3,3-dimethylpentanoic acid
  参考文献：
  名称：

  [EN] ARYLAMIDES AND METHODS OF USE THEREOF
  [FR] ARYLAMIDES ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  本公开涉及杂环化合物，其药用盐以及药物制剂。本文还描述了这些化合物的组成以及在治疗由CFTR活性缺陷介导的疾病和病况的方法中的使用，特别是囊性纤维化。

  公开号：

  WO2021113806A1

文献信息

• The asymmetric synthesis of allylglycine and other unnatural α-amino acids via zinc-mediated allylation of oximes in aqueous media
  作者：Stephen Hanessian、Rui-Yang Yang

  DOI：10.1016/0040-4039(96)01118-5

  日期：1996.7

  Enantiomerically pure or highly enriched allylglycine and its chain-substituted analogs are easily accessible from the reaction of the sultam derivative of O-benzyl glyoxylic acid oxime with allylic bromides in the presence of powdered zinc in aqueous ammonium chloride.

  对映体纯的或高度富集的烯丙基甘氨酸及其链取代的类似物，在粉末状的锌在氯化铵水溶液中的存在下，很容易从O-苄基乙醛酸肟的磺胺衍生物与烯丙基溴的反应中获得。
• Preparation of α-Amino Acids by Oxidative Oxazoline-Oxazinone Rearrangement-Hydrogenation (OOOH). Scope and Limitations
  作者：Chaomin Liu、Tadeusz F. Molinski

  DOI：10.1002/asia.201100452

  日期：2011.8.1

  The range and scope of the oxidative oxazoline–oxazinone rearrangement–hydrogenation sequence (OOOH)—a short, direct asymmetric synthesis of α‐amino acids from carboxylic acids—was explored. The highest yet reported diastereoselectivity for hydrogenation of the oxazinone CN bond (d.r.=>80:1) is disclosed and rationalized with the aid of ab initio molecular calculations.

  研究了氧化恶唑啉-恶嗪酮重排-氢化序列（OOOH）的范围和范围，即由羧酸短而直接地不对称合成α-氨基酸。公开了迄今报道的最高的对恶嗪酮C hydrogenN键氢化的非对映选择性（dr => 80：1），并借助从头算分子的方法使之合理化。
• Total synthesis of the large non-ribosomal peptide polytheonamide B
  作者：Masayuki Inoue、Naoki Shinohara、Shintaro Tanabe、Tomoaki Takahashi、Ken Okura、Hiroaki Itoh、Yuki Mizoguchi、Maiko Iida、Nayoung Lee、Shigeru Matsuoka

  DOI：10.1038/nchem.554

  日期：2010.4

  Polytheonamide B is by far the largest non-ribosomal peptide known at present, and displays extraordinary cytotoxicity (EC50 = 68 pg ml−1, mouse leukaemia P388 cells). Its 48 amino-acid residues include a variety of non-proteinogenic d- and l-amino acids, and the absolute stereochemistry of these amino acids alternate in sequence. These structural features induce the formation of a stable β-strand-type structure, giving rise to an overall tubular structure over 30 Å in length. In a biological setting, this fold is believed to transport cations across the lipid bilayer through a pore, thereby acting as an ion channel. Here, we report the first chemical construction of polytheonamide B. Our synthesis relies on the combination of four key stages: syntheses of non-proteinogenic amino acids, a solid-phase assembly of four fragments of polytheonamide B, silver-mediated connection of the fragments and, finally, global deprotection. The synthetic material now available will allow studies of the relationships between its conformational properties, channel functions and cytotoxicity. Polytheonamide B is a large non-ribosomal peptide with very high bioactivity. The synthesis described here includes the first preparation of several non-proteinogenic amino acids and a general coupling strategy for large non-natural peptides. The synthesis is a key step necessary to understand and utilize the bioactivity of this and similar compounds.

  聚糖酰胺 B 是目前已知的最大的非核糖体肽，具有非凡的细胞毒性（EC50 = 68 pg mlâ1, 小鼠白血病 P388 细胞）。它的 48 个氨基酸残基包括多种非蛋白原性 d 和 l 氨基酸，这些氨基酸的绝对立体化学结构依次交替。这些结构特征促使形成稳定的δ-strand 型结构，从而形成长度超过 30 Ã 的整体管状结构。在生物环境中，这种折叠结构被认为可以通过一个孔隙在脂质双分子层中运输阳离子，从而起到离子通道的作用。在此，我们首次报告了聚神酰胺 B 的化学结构。我们的合成依赖于四个关键阶段的结合：非蛋白源氨基酸的合成、聚草酰胺 B 四个片段的固相组装、银介导的片段连接以及最后的全局脱保护。现在可用的合成材料将有助于研究其构象特性、通道功能和细胞毒性之间的关系。聚神酰胺 B 是一种大型非核糖体多肽，具有极高的生物活性。本文描述的合成包括首次制备几种非蛋白源氨基酸和大型非天然肽的一般偶联策略。该合成是了解和利用该化合物及类似化合物生物活性的关键一步。
• [EN] CYCLIC PEPTIDES FOR PROTECTION AGAINST RESPIRATORY SYNCYTIAL VIRUS<br/>[FR] PEPTIDES CYCLIQUES POUR LA PROTECTION CONTRE LE VIRUS RESPIRATOIRE SYNCYTIAL
  申请人：VIROMETIX AG

  公开号：WO2018229156A1

  公开（公告）日：2018-12-20

  The present invention relates to a cyclic peptide, a conjugate comprising said cyclic peptide and a lipopeptide building block, a bundle of said conjugates, a synthetic virus-like particle comprising at least one bundle of conjugates and pharmaceutical compositions comprising the same. The present invention further relates to said cyclic peptide, said conjugate said bundle of conjugates, said synthetic virus-like particle and said pharmaceutical compositions for use as a medicament, preferably for use in a method for preventing of an infectious disease or reducing the risk of an infectious disease, more preferably for use in a method for preventing or reducing the risk of an infectious disease associated with or caused by a respiratory syncytial virus. In particular, the present invention relates to a cyclic peptide, wherein said cyclic peptide comprises an amino acid sequence (I), wherein said amino acid sequence (I) comprises the following amino acid sequence: X1-X2-X3-C4-X5-X6-X7-C8-X9-X10-X11-P12-I13-T14-N15-D16-Q17-K18-K19-L20-C21- X22-X23-X24-C25-X26-X27-X28-X29-X30 (SEQ ID NO: 1), wherein X1, X2, X3, X5, X6, X7, X9, X10, X11, X22, X23, X24, X26, X27, X28 and X29 are independently of each other an amino acid; C4, C8, C21 and C25 are independently of each other cysteine; P12 is proline; I13 is isoleucine; T14 is threonine; N15 is asparagine; D16 is aspartic acid; Q17 is glutamine; K18 and K19 are independently of each other lysine; L20 is leucine; and X30 is an amino acid or a deletion, wherein said cysteines C4 and C25 form a first disulfide bond and said cysteines C8 and C21 form a second disulfide bond.

  本发明涉及一种环肽，一种包含所述环肽和脂肽肽基的结合物，一束所述结合物，一种合成的类病毒颗粒，其中包括至少一个结合物束以及包含它们的制药组合物。本发明还涉及该环肽，该结合物，该结合物束，该合成的类病毒颗粒和该制药组合物作为药物的用途，优选用于预防传染病或降低传染病风险的方法，更优选用于预防或降低与呼吸道合胞病毒相关或由其引起的传染病的方法。特别地，本发明涉及一种环肽，其中所述环肽包括氨基酸序列(I)，其中所述氨基酸序列(I)包括以下氨基酸序列：X1-X2-X3-C4-X5-X6-X7-C8-X9-X10-X11-P12-I13-T14-N15-D16-Q17-K18-K19-L20-C21-X22-X23-X24-C25-X26-X27-X28-X29-X30(SEQ ID NO:1)，其中X1、X2、X3、X5、X6、X7、X9、X10、X11、X22、X23、X24、X26、X27、X28和X29分别是氨基酸；C4、C8、C21和C25分别是半胱氨酸；P12是脯氨酸；I13是异亮氨酸；T14是苏氨酸；N15是天冬氨酸；D16是天冬酸；Q17是谷氨酰胺；K18和K19分别是赖氨酸；L20是亮氨酸；X30是氨基酸或缺失，其中所述半胱氨酸C4和C25形成第一二硫键，所述半胱氨酸C8和C21形成第二二硫键。
• Total Synthesis of Polydiscamides B, C, and D via a Convergent Native Chemical Ligation–Oxidation Strategy
  作者：Gajan Santhakumar、Richard J. Payne

  DOI：10.1021/ol502045u

  日期：2014.9.5

  The first total syntheses of the marine sponge-derived cyclic depsipeptide natural products Polydiscamides B, C, and D are described. The molecules were constructed through the convergent fusion of cyclic and linear fragments via an unprecedented native chemical ligation–oxidation protocol.

  描述了海洋海绵衍生的环状二肽天然产物Polydiscamides B，C和D的第一批合成。这些分子是通过前所未有的天然化学连接-氧化方案，通过环状和线性片段的融合融合而构建的。