N-<(R)-1'-phenyl-2'-hydroxyethyl>-(1S)-methylenecyclopropanecarboxamide | 127103-94-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-<(R)-1'-phenyl-2'-hydroxyethyl>-(1S)-methylenecyclopropanecarboxamide
• 英文别名: (1S)-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylidenecyclopropane-1-carboxamide
• CAS: 127103-94-0
• 化学式: C₁₃H₁₅NO₂
• 分子量: 217.268
• InChiKey: BCLQUHIPAQVTFV-RYUDHWBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-<(R)-1'-phenyl-2'-hydroxyethyl>-(1S)-methylenecyclopropanecarboxamide 在 硫酸 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 50.0h， 生成 (2S)-2-benzyloxycarbonylamino-4-[(S)-2-methylenecyclopropane-1-carbonylperoxy]-4-oxo-butyric acid methyl ester
  参考文献：
  名称：

  通过二酰基过氧化物的光解合成β-环丙基丙氨酸。

  摘要：

  [反应：参见正文] 254纳米（无溶剂）衍生自环丙烷羧酸和l-天冬氨酸的纯净（不溶剂）不对称二酰基过氧化物的光解以合理的收率生成了受保护的β-环丙基丙氨酸。通过这种方法，可以合成抗肿瘤药物贝洛糖素A的关键成分的正交保护的3-（反式-2-氨基环丙基）丙氨酸（21）和牙买加呕吐病的病原体受保护的次糖苷A（26）。中间取代的环丙基自由基的偶联主要在保留构型的情况下进行（dr>或= 95：5）。

  DOI：

  10.1021/ol035859a
• 作为产物：
  描述：

  2-溴-2-甲基环丙烷-1-羧酸乙酯 在 氢氧化钾 、 乙醇 、 sodium hydride 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 水 为溶剂， 反应 18.0h， 生成 N-<(R)-1'-phenyl-2'-hydroxyethyl>-(1S)-methylenecyclopropanecarboxamide
  参考文献：
  名称：

  （R）-（-）-和（S）-（+）-Synadenol：抗病毒作用的合成，绝对构型和对映选择性。

  摘要：

  描述了（R）-（-）-和（S）-（+）-香豆酚（1a和2a，95-6％ee）的合成。用腺苷脱氨酶将消旋的西地那醇（1a + 2a）脱氨基，得到（R）-（-）-synadenol（1a）和（S）-（+）-次黄嘌呤衍生物5。乙酰化后者化合物，得到乙酸酯6.与N，N-二甲基氯亚甲基氯化铵制得6-氯嘌呤衍生物7。氨解提供了（S）-（+）-synadenol（2a）。通过两种方法确定1a的绝对构型：（i）由（R）-亚甲基环丙烷羧酸（8）合成，以及（ii）（-）-香豆酚盐酸盐单晶的X射线衍射。外消旋的亚甲基环丙烷羧酸（10）通过描述的方法的改变而拆分。将R-对映异构体8转化为乙酯13，将其溴化，得到邻二溴化物14。用二异丁基氢化铝还原，然后得到醇15，将其乙酰化为相应的乙酸酯16。用16的腺嘌呤烷基化消除过程产生乙酸酯17和18。用氨脱保护得到R的Z-和E-异构体1a和19的混合物。 -配置。通过手性

  DOI：

  10.1021/jm980323u

文献信息

• Studies on the Inactivation of Bovine Liver Enoyl-CoA Hydratase by (Methylenecyclopropyl)formyl-CoA:  Elucidation of the Inactivation Mechanism and Identification of Cysteine-114 as the Entrapped Nucleophile
  作者：Srikanth Dakoji、Ding Li、Gautam Agnihotri、Hui-qiang Zhou、Hung-wen Liu

  DOI：10.1021/ja011226k

  日期：2001.10.1

  (R)- and (S)-diastereomers of MCPF-CoA to examine the stereoselectivity of this inactivation. Both compounds were shown to be competent inhibitors for bovine liver ECH with nearly identical second-order inactivation rate constants (k(inact)/K(I)) and partition ratios (k(cat)/k(inact)), indicating that the inactivation is nonstereospecific with respect to ring cleavage. The inhibitor, upon incubation

  （亚甲基环丙基）甲酰辅酶 A (MCPF-CoA) 是一种天然氨基酸（亚甲基环丙基）甘氨酸的代谢物，对牛肝烯酰辅酶 A 水合酶 (ECH) 的抑制特性进行了表征。我们之前已经证明 MCPF-CoA 专门针对 ECH，它催化 alpha,beta-不饱和烯酰-CoA 底物可逆地水合为相应的 β-羟酰基-CoA 产物。在这里，我们合成了 MCPF-CoA 的 (R)-和 (S)-非对映异构体，以检查这种失活的立体选择性。两种化合物均被证明是牛肝 ECH 的有效抑制剂，具有几乎相同的二级失活速率常数 (k(inact)/K(I)) 和分配比 (k(cat)/k(inact))，表明失活在环裂解方面是非立体特异性的。抑制剂，与牛肝 ECH 孵育后，在蛋白质活性位点附近标记胰蛋白酶肽 ALGGGXEL，其中 X 是共价修饰的氨基酸。牛肝 ECH 基因的克隆和序列分析揭示了被 MCPF-CoA 捕获的氨基酸残基的身份为
• Lai, Ming-Tain; Liu, Hung-Wen, Journal of the American Chemical Society, 1990, vol. 112, # 10, p. 4034 - 4035
  作者：Lai, Ming-Tain、Liu, Hung-Wen

  DOI：——

  日期：——
• Mechanistic study on the inactivation of general acyl-CoA dehydrogenase by a metabolite of hypoglycin A
  作者：Ming Tain Lai、Li Da Liu、Hung Wen Liu

  DOI：10.1021/ja00019a040

  日期：1991.9

  General acyl-CoA dehydrogenase (GAD) is a flavin-dependent (FAD) enzyme that catalyzes the oxidation of a fatty acyl-CoA to the corresponding alpha,beta-enolyl-CoA. When GAD is exposed to (methylenecyclopropyl)acetyl-CoA (MCPA-CoA), a metabolite of hypoglycin A that is the causative agent of Jamaican vomiting sickness, time-dependent inhibition occurs with concomitant bleaching of the active-site FAD. The inactivation mechanism is generally believed to be initiated by C-alpha anion formation followed by ring fragmentation and the covalent modification of FAD. However, formation of a cyclopropyl radical intermediate through one-electron oxidation followed by ring opening and then radical recombination to yield a modified FAD is an appealing alternative. As described herein, studies of the inactivation of GAD by (1S)- and (1R)-MCPA-CoA bearing a stereospecific tritium label at C-alpha have provided direct evidence suggesting that C-alpha proton abstraction occurs during inactivation and the two diastereomers of MCPA-CoA bind to the same locus in the active site of GAD. Despite the fact that the inactivations mediated by (1R)- and (1S)-MCPA-CoA proceed at different rates, the observed partition ratios are almost identical. Using [alpha,alpha-H-2(2)]MCPA-CoA as inhibitors, we have found that the sluggish inactivation observed for (1S)-MCPA-CoA is not due to mechanistic rerouting, but is instead a result of the retardation of the initial deprotonation step. Thus, the equivalent partition ratios found in these studies clearly indicate that inactivation by either (1R)- or (1S)-MCPA-CoA follows the same chemical course. Such a lack of stereospecificity for the bond rupture at C-beta of MCPA-CoA in the enzyme active site suggests that the ring-opening step leading to inactivation is likely a spontaneous event. Since the rearrangement of alpha-cyclopropyl radicals to ring-opened alkyl radicals is extremely rapid, the ring cleavage induced by an alpha-cyclopropyl radical may bypass the chiral discrimination normally imposed by the enzyme. Thus, the mechanistic insights deduced from this study support our early notion that inactivation of GAD by MCPA-CoA is likely to proceed through a radical mechanism.
• LAI, MING-TAIN;LIU, HUNG-WEN, J. AMER. CHEM. SOC., 112,(1990) N0, C. 4034-4035
  作者：LAI, MING-TAIN、LIU, HUNG-WEN

  DOI：——

  日期：——