(E)-4-amino-2-(hydroxymethyl)-2-butenoic hydrochloride | 100702-77-0

• 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: (E)-4-amino-2-(hydroxymethyl)-2-butenoic hydrochloride
• CAS: 100702-77-0
• 化学式: C₅H₉NO₃*ClH
• 分子量: 167.592
• InChiKey: GAXAGELWRGPQCO-DYVSEJHDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.63
• 重原子数：
  10.0
• 可旋转键数：
  3.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  83.55
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  tert-butyl 4-<(benzyoxycarbonyl)amino>-2-(hydroxymethyl)-2-(phenylseleno)butanoate 在 盐酸 、 二异丙胺 、 间氯过氧苯甲酸 作用下， 以 三氟乙酸 为溶剂， 反应 2.08h， 生成 (E)-4-amino-2-(hydroxymethyl)-2-butenoic hydrochloride
  参考文献：
  名称：

  4-Amino-2-(substituted methyl)-2-butenoic acids: substrates and potent inhibitors of .gamma.-aminobutyric acid aminotransferase

  摘要：

  4-Amino-2-(substituted methyl)-2-butenoic acids, where X (the substituted group) = F, Cl, OH, are synthesized from Cbz-protected tert-butyl 4-aminobutanoate. Successive substitutions at the alpha-carbon by phenylseleno and hydroxymethyl groups, followed by elimination of the selenoxide and halide substitution at the hydroxymethyl group, afford the compounds in good yields. An unexpected degree of stereoselectivity is observed in the selenoxide elimination step, which yields the desired E isomer as the sole product. These compounds complement two previously reported series of compounds (Silverman, R. B.; Levy, M. A. Biochem. Biophys. Res. Commun. 1980, 95, 250-255; J. Biol. Chem. 1981, 256, 11 565-11 568) and are used in an approach to map a section of the active site of gamma-aminobutyric acid aminotransferase (GABA-T). None of these compounds is a time-dependent inactivator of GABA-T, but all are potent competitive reversible inhibitors; the hydroxy compound has a Ki value of 5 microM. That these compounds are not inactivators suggests that either elimination of X does not occur or that there is no active site nucleophile in the appropriate position for reaction following elimination. With use of the fluoro analogue, enzyme-catalyzed fluoride ion release is demonstrated, indicating that elimination does occur. Unlike the previous two series of compounds (op. cit.) in which exclusive elimination occurs when the substituent is a halogen but exclusive transamination prevails for the hydroxyl-substituted analogues, in the series described here, the fluoro analogue gives a 4:1 ratio of elimination to transamination. This suggests that the 2,3-double bond stabilizes the product of azallylic isomerization of the Schiff base between the fluoro compound and pyridoxal phosphate. The results described here indicate that the design of a mechanism-based inactivator for GABA-T should not be based on electrophile generation near the 2-position of enzyme-bound GABA. Furthermore, substitution of an inhibitor with a 2-hydroxymethyl group (or other hydrogen-bonding substituent) and a 2,3-double bond may lend auspicious binding properties to the molecule for GABA-T.

  DOI：

  10.1021/jm00155a029