3-乙酰基硫基-2-甲基丙酸 | 74431-52-0

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 3-乙酰基硫基-2-甲基丙酸
• 英文名称: (R)-3-acetylsulfanyl-2-methyl-propionic acid
• 英文别名: (R)-3-acetylsulfanyl-2-methylpropionic acid；(R)-acetyl-β-mercaptoisobutyric acid；(S)-(-)-3-acetylthio-2-methylpropionic acid；(2R)-3-(acetylthio)-2-methylpropanoic acid；(R)-(-)-S-acetyl-3-mercaptoisobutyric acid；(2R)-3-acetylthio-2-methylpropionic acid；(R)-3-(Acetylthio)-2-methylpropionic acid；(2R)-3-acetylsulfanyl-2-methylpropanoic acid
• CAS: 74431-52-0
• 化学式: C₆H₁₀O₃S
• 分子量: 162.21
• InChiKey: VFVHNRJEYQGRGE-BYPYZUCNSA-N

物化性质

• 沸点：
  276.5±23.0 °C(Predicted)
• 密度：
  1.213±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  79.7
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2930909090

反应信息

• 作为反应物：
  描述：

  3-乙酰基硫基-2-甲基丙酸 在 吡啶 、 氯化亚砜 作用下， 以 甲苯 为溶剂， 反应 1.5h， 生成 3-乙酰硫基-2-甲基丙酰氯
  参考文献：
  名称：

  Angiotensin-converting enzyme inhibitors. New orally active antihypertensive (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives

  摘要：

  A variety of N-substituted (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives was synthesized and their ability in inhibiting the activity of angiotensin-converting enzyme (ACE) was examined in vitro and in vivo. The acylthio derivatives prepared are assumed to act as prodrugs since they are much less active than the corresponding free SH compounds in vitro and can be expected to act in vivo only after conversion to the free sulfhydryl compounds. A number of these compounds are potent ACE inhibitors that lowered blood pressure in Na-deficient, conscious spontaneously hypertensive rats (SHR), a high renin model. One of the most active members of the series was (S)-N-cyclopentyl-N-[3-[(2,2-dimethyl-1-oxopropyl)thio]-2-methyl-1 -oxopropyl]glycine (REV 3659-(S), pivopril). Structure-activity relationships are discussed.

  DOI：

  10.1021/jm00379a013
• 作为产物：
  描述：

  (2R)-3-acetylsulfanyl-2-methylpropanoic acid;(2R)-3-phenyl-2-(propan-2-ylamino)propan-1-ol 生成 3-乙酰基硫基-2-甲基丙酸
  参考文献：
  名称：

  SAWAYAMA, TADAHIRO;TSUKAMOTO, MASATOSHI;SASAGAWA, TAKASHI;NARUTO, SHUNSUK+, CHEM. AND PHARM. BULL., 37,(1989) N, C. 1382-1383

  摘要：

  DOI：

文献信息

• [EN] MACROCYCLIC LACTAMS AND PHARMACEUTICAL USE THEREOF<br/>[FR] LACTAMES MACROCYCLIQUES ET LEUR UTILISATION PHARMACEUTIQUE
  申请人：NOVARTIS AG

  公开号：WO2005049585A1

  公开（公告）日：2005-06-02

  The present invention relates to novel macrocyclic compounds of the formula (I) wherein R1, R2, R3, U, V, W, X, Y, Z and n are as defined in the specification, the number of ring atoms included in the macrocyclic ring being 14, 15, 16 or 17, in free base form or in acid addition salt form, to their preparation, to their use as pharmaceuticals and to pharma­ceutical compositions comprising them.

  本发明涉及以下式（I）的新型大环化合物，其中R1、R2、R3、U、V、W、X、Y、Z和n如规范中所定义，大环环中包含的环原子数为14、15、16或17，以自由碱形式或酸盐形式存在，以及它们的制备方法，用作药物的用途，以及包含它们的药物组合物。
• Organocatalytic enantioselective transient enolate protonation in conjugate addition of thioacetic acid to α-substituted N-acryloyloxazolidinones
  作者：Rajshekhar A. Unhale、Nirmal K. Rana、Vinod K. Singh

  DOI：10.1016/j.tetlet.2013.01.004

  日期：2013.4

  Organocatalytic conjugate addition of thioacetic acid to a series of α-substituted N-acryloyloxazolidin-2-ones followed by enantioselective protonation has been studied in the presence of thiourea catalysts derived from cinchona alkaloids. Conjugate addition/protonation adducts have been obtained up to 97% ee and high yields. The methodology could serve as an easy and practical route to the syntheses

  在衍生自金鸡纳生物碱的硫脲催化剂存在下，已经研究了将硫代乙酸有机催化共轭加成到一系列α-取代的N-丙烯酰基恶唑烷丁二酮中，然后进行对映选择性质子化。已经获得了高达97％ee且高收率的共轭加成/质子化加合物。该方法可以作为合成有用的生物活性分子的简便实用途径。
• Structural Basis of Metallo-β-Lactamase Inhibition by Captopril Stereoisomers
  作者：Jürgen Brem、Sander S. van Berkel、David Zollman、Sook Y. Lee、Opher Gileadi、Peter J. McHugh、Timothy R. Walsh、Michael A. McDonough、Christopher J. Schofield

  DOI：10.1128/aac.01335-15

  日期：2016.1

  enzyme inhibition, has been reported to inhibit MBLs by chelating the active site zinc ions via its thiol(ate). We report systematic studies on B1 MBL inhibition by all four captopril stereoisomers. High-resolution crystal structures of three MBLs (IMP-1, BcII, and VIM-2) in complex with either the l- or d-captopril stereoisomer reveal correlations between the binding mode and inhibition potency.

  β-内酰胺是最成功的抗菌剂，但它们的有效性受到耐药性的威胁，最重要的是产生丝氨酸和金属β-内酰胺酶 (MBL)。MBLs 越来越受到关注，因为它们催化几乎所有 β-内酰胺类抗生素的水解，包括最近一代的碳青霉烯类。已开发出临床有用的丝氨酸-β-内酰胺酶抑制剂，但此类抑制剂不适用于 MBL。l-Captopril 用于通过抑制血管紧张素转换酶来治疗高血压，据报道它通过其硫醇（酸盐）螯合活性位点锌离子来抑制 MBL。我们报告了所有四种卡托普利立体异构体对 B1 MBL 抑制的系统研究。三种 MBL 的高分辨率晶体结构（IMP-1、BcII、和 VIM-2) 与 l- 或 d- 卡托普利立体异构体复合揭示了结合模式和抑制效力之间的相关性。该结果将有助于设计具有广泛选择性的 MBL 抑制剂，用于临床应用对抗耐碳青霉烯类肠杆菌科细菌和其他引起 MBL 介导的耐药性感染的生物体。
• [EN] MACROCYCLIC COMPOUNDS HAVING ASPARTIC PROTEASE INHIBITING ACTIVITY AND PHARMACEUTICAL USES THEREOF<br/>[FR] COMPOSES MACROCYLIQUES PRESENTANT UNE ACTIVITE D'INHIBITION DE PROTEASE ASPARTIQUE ET UTILISATIONS PHARMACEUTIQUES DE CEUX-CI
  申请人：NOVARTIS AG

  公开号：WO2005003106A1

  公开（公告）日：2005-01-13

  The present invention relates to macrocyclic compounds of formula (I), wherein R1, is (C1-8)alkyl, (C1-4)alkoxy(C1-4)alkyl, hydroxy(C1-6)alkyl, (C1-4)alkylthio(C1-4)alkyl, (C1-6)alkenyl, (C3-­7)cycloalkyl, (C3-7)cycloalkyl(C1-4)alkyl, piperidinyl or pyrrolidinyl, R2 and R4, independently, are hydrogen or optionally substituted (C1-8)alkyl, (C3-7) cycloalkyl, (C3-7)cycloalkyl(C1-4)alkyl, aryl, aryl(C1-4)alkyl, heteroaryl or heteroaryl(C1-4) alkyl, or R2 and R4, together with the nitrogen to which they are attached, form an optionally substituted piperidino, pyrrolidinyl, morpholino or piperazinyl group, R3 is hydrogen or (C1-4)alkyl, X1 is CH2, X2 is CH2, O, S, CO, COO, OCO, NHCO, CONH, or NR, R being hydrogen or (C1-4)alkyl, Y is (C1-8)alkylen or (C1-­8)alkylenoxy(C1-6)alkylen, (C1-8)alkenylen or (C1-8)alkenylenoxy(C1-6)alkylen, Ar is a phenyl ring optionally mono- di­ or trisubstituted by, independently, hydroxy or halogen, whereby X1, and X2 are in meta or para position to each other, and either Z is CO, AA is a natural or unnatural alpha-amino-acid, and n is 0 or 1, or Z is S02, AA is an optionally substituted ethylencarbonyl group (derived from a natural or unnatural alpha-amino acid by replacement of the nitrogen by a methylen group), and n is 1; processes for the preparation of these compounds; pharmaceutical compositions and combinations comprising the same; and their use in the treatment of neurological and vascular disorders related to beta-amyloid generation and/or aggregation.

  本发明涉及式(I)的大环化合物，其中R1为(C1-8)烷基，(C1-4)烷氧基(C1-4)烷基，羟基(C1-6)烷基，(C1-4)烷基硫基(C1-4)烷基，(C1-6)烯基，(C3-7)环烷基，(C3-7)环烷基(C1-4)烷基，哌啶基或吡咯啉基，R2和R4，独立地，为氢或可选择取代的(C1-8)烷基，(C3-7)环烷基，(C3-7)环烷基(C1-4)烷基，芳基，芳基(C1-4)烷基，杂环芳基或杂环芳基(C1-4)烷基，或R2和R4与它们连接的氮一起形成可选择取代的哌啶基，吡咯啉基，吗啉基或哌嗪基，R3为氢或(C1-4)烷基，X1为CH2，X2为 ，O，S，CO，COO，OCO，NHCO，CONH或NR，R为氢或(C1-4)烷基，Y为(C1-8)烷基或(C1-8)烷氧基(C1-6)烷基，(C1-8)烯基或(C1-8)烯氧基(C1-6)烷基，Ar为苯环，可选择单取代、双取代或三取代，取代基为羟基或卤素，其中X1和X2在彼此的间位或对位，且Z为CO时，AA为天然或非天然的α-氨基酸，n为0或1；或Z为SO2时，AA为可选择取代的乙烯羰基团（由天然或非天然的α-氨基酸通过用甲基烷基替换氮而得到），n为1；制备这些化合物的方法；包含这些化合物的药物组合物和药物组合物；以及它们在治疗与β-淀粉样蛋白生成和/或聚集相关的神经和血管疾病中的用途。
• Steroselective Hydrolysis of DL-Beta-Acetylthioisobutyramide Catalyzed by Genetically Engineered<i>E. Coli</i>Immobilized on Celite 580 in a Packed Bed Bioreactor
  作者：Shyh-Yu Shaw、Yu-Jen Chen、Jung-Jung Ou、Lewis Ho

  DOI：10.1002/jccs.200700227

  日期：2007.12

  filled with Celite 580. The packed bed bioreactor was used to conduct the stereoselective hydrolysis of dl-ATIA and to give DAT with a yield of 34.5%, enantiometric excess value of 97% and enantioselectivity value > 150. The optimal pH and temperature for the reaction were 9.0 and 57 °C ∼ 67 °C, respectively. The kinetic constants (Km and Vmax) of immobilized cells were found to be 372.5 mM and 285.7 μmol

  恶臭假单胞菌 IFO12996 催化甲基 dl-β-乙酰硫代异丁酰胺 (dl-ATIA) 的立体选择性水解形成 d-β-乙酰硫代异丁酸 (DAT)，它是合成一系列血管紧张素转化酶抑制剂的关键中间体。将恶臭假单胞菌 IFO12996 酯酶基因克隆并在大肠杆菌中表达，将其进一步固定化并保留在填充有硅藻土 580 的填充床生物反应器中。填充床生物反应器用于进行 dl-ATIA 的立体选择性水解，得到 DAT 与产率为 34.5%，对映过量值为 97%，对映选择性值 > 150。反应的最佳 pH 值和温度分别为 9.0 和 57°C ∼ 67°C。发现固定化细胞的动力学常数（Km 和 Vmax）分别为 372.5 mM 和 285.7 μmol min-1（g 细胞）-1。在 5 个批次生产周期后，固定化细胞保留了超过 60% 的初始催化活性。本文介绍了一种将基因工程大肠杆菌固定在新型填充床生物反应器上生产