(R)-(+)-Methylenecyclopropylmethanol | 127103-95-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (R)-(+)-Methylenecyclopropylmethanol
• 英文别名: [(1R)-2-methylidenecyclopropyl]methanol
• CAS: 127103-95-1
• 化学式: C₅H₈O
• 分子量: 84.1179
• InChiKey: CQFQAARMEJVWAL-YFKPBYRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  6
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (R)-(+)-Methylenecyclopropylmethanol 在 15-冠醚-5 、 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 1.17h， 生成 (1S)-(-)-methylenecyclopropaneacetonitrile
  参考文献：
  名称：

  Mechanistic study on the inactivation of general acyl-CoA dehydrogenase by a metabolite of hypoglycin A

  摘要：

  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.

  DOI：

  10.1021/ja00019a040
• 作为产物：
  描述：

  亚甲基环丙烷-2-羧酸 在 lithium aluminium tetrahydride 、 硫酸 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 8.0h， 生成 (R)-(+)-Methylenecyclopropylmethanol
  参考文献：
  名称：

  Mechanistic study on the inactivation of general acyl-CoA dehydrogenase by a metabolite of hypoglycin A

  摘要：

  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.

  DOI：

  10.1021/ja00019a040

文献信息

• Ru(II)‐Pheox Catalyzed Highly Stereoselective Cyclopropanation of Allyl‐ and Vinylsilanes with Diazoesters and Their Synthetic Applications
  作者：Nansalmaa Otog、Hayato Inoue、Doan Thi Thuy Trinh、Zolzaya Batgerel、Niklas Maximilian Langendorf、Ikuhide Fujisawa、Seiji Iwasa

  DOI：10.1002/cctc.202001427

  日期：2021.1.12

  catalyst for cyclopropanation reactions of diazoesters with various allylsilanes. Also, methyl(diazoacetoxy)acetate afforded in significantly enhanced yields, diastereoselectivities, and enantioselectivities. The cyclopropanation reactions with vinylsilanes with methyl (diazoacetoxy)acetate proceeded with excellent diastereoselectivities (>99 : 1 d.r.). Moreover, cyclopropylsilane derivatives could be successfully

  由各种烯丙基和乙烯基硅烷与官能化的重氮酸酯进行立体选择性合成的光学活性环丙基硅烷，具有优异的收率（高达99％）和非对映异构体（高达> 99：1 dr）和对映选择性（高达99％ee）。 Ru（II）-Pheox催化剂的存在。在一系列Ru（II）-Pheox催化剂中，p-MeO-Ru（II）-Pheox被确定为重氮酸酯与各种烯丙基硅烷的环丙烷化反应的最佳催化剂。同样，（重氮乙酰氧基）乙酸甲酯的产率，非对映选择性和对映选择性也大大提高。用乙烯基硅烷与（重氮乙酰氧基）乙酸甲酯进行的环丙烷化反应具有出色的非对映选择性（> 99：1 dr）。此外，环丙基硅烷衍生物可以成功地转化为合成生物活性化合物的有益构件，包括抗HIV药物和Imatinib-7。
• [EN] (+)-TRANS-ISOMERS OF (1-PHOSPHONOMETHOXY-2-ALKYLCYCLOPROPYL) METHYL NUCLEOSIDE DERIVATIVES, PROCESS FOR THE PREPARATION OF STEREOISOMERS THEREOF, AND USE OF ANTIVIRAL AGENTS THEREOF<br/>[FR] TRANS-ISOMERES (+) DE DERIVES DE NUCLEOSIDE ( 1-PHOSPHONOMETHOXY-2-ALKYLCYCLOPROPYL)METHYLE, PROCESSUS DE PREPARATION DE STEREO-ISOMERES DE CEUX-CI ET UTILISATION D'AGENTS ANTIVIRAUX A BASE CEUX-CI
  申请人：LG LIFE SCIENCES LTD

  公开号：WO2004029064A1

  公开（公告）日：2004-04-08

  The present invention relates to (+)-trans-isomers of (1-phosphonomethoxy-2- alkylcyclopropyl)methyl nucleoside derivatives of the formula (1) which are useful as an antiviral agent (particularly, against hepatitis B virus), pharmaceutically acceptable saltss, hydrates, or solvates thereof, and processes for the preparation of stereoisomers of the compounds of the formula (1), and a composition for the treatment of viral diseases (particularly, against hepatitis B virus) comprising (+)-trans-isomer of the compound of the formula (1), pharmaceutically acceptable salt, hydrate, or solvate thereof as an active substance.

  本发明涉及公式（1）的（+）-反式异构体（1-磷酸甲氧基-2-烷基环丙基）甲基核苷衍生物，该衍生物可用作抗病毒剂（特别是对乙型肝炎病毒），其药用盐、水合物或溶剂化合物，以及用于制备公式（1）化合物的立体异构体的方法，以及一种用于治疗病毒性疾病（特别是对乙型肝炎病毒）的组合物，包括公式（1）化合物的（+）-反式异构体，其药用盐、水合物或溶剂化合物作为活性物质。
• Asymmetric total synthesis of the individual diastereoisomers of hypoglycin A
  作者：Jack E. Baldwin、Robert M. Adlington、David Bebbington、Andrew T. Russell

  DOI：10.1039/c39920001249

  日期：——

  The individual diastereoisomers that constitute the unusual methylenecyclopropane containing α-amino acid hypoglycin A have been synthesised utilising the Sharpless epoxidation to permit an asymmetric methylene cyclopropane synthesis.

  利用Sharpless环氧化法合成了构成非寻常的含有α-氨基酸次糖苷A的不寻常的亚甲基环丙烷的各个非对映异构体，以允许不对称的亚甲基环丙烷的合成。
• Asymmetric total synthesis of the individual diastereoisomers of hypoglycin A.
  作者：Jack E. Baldwin、Robert M. Adlington、David Bebbington、Andrew T. Russell

  DOI：10.1016/s0040-4020(01)89313-3

  日期：1994.1

  The individual diastereoisomers that constitute the unusual methylenecyclopropane containing α-amino acid hypoglycin A have been synthesised utilising the Sharpless epoxidation to permit an asymmetric methylenecyclopropane synthesis.

  利用Sharpless环氧化法合成了构成非寻常的含有α-氨基酸次糖苷A的不寻常的亚甲基环丙烷的各个非对映异构体，以允许不对称的亚甲基环丙烷的合成。
• Revision of Absolute Configuration of Enantiomeric (Methylenecyclopropyl)carbinols Obtained from (<i>R</i>)-(−)- and (<i>S</i>)-(+)-Epichlorohydrin and Methylenetriphenylphosphorane. Implications for Reaction Mechanism and Improved Synthesis of Antiviral Methylenecyclopropane Analogues of Nucleosides
  作者：Xinchao Chen、Jiri Zemlicka

  DOI：10.1021/jo010511j

  日期：2002.1.1

  reaction of (R)- and (S)-epichlorohydrin 5 with methylenetriphenylphosphorane or resolution of the corresponding oxaphospholane 6 via a salt with L-(+)-tartaric acid and subsequent Wittig transformation with formaldehyde were revised. The (-)-oxaphospholane 6 has the S,S and (-)-(methylenecyclopropyl)carbinol (4) the R configuration. The configurations of (+)-6 and (+)-4 are then R,R and S, respectively

  修订了通过（R）-和（S）-表氯醇5与亚甲基三苯基膦烷反应或通过与L-（+）-酒石酸的盐拆分相应的氧杂膦烷6并随后用甲醛进行Wittig转化而获得的对映异构体亚甲基环丙烷甲醇的绝对构型。（-）-氧杂膦烷6具有S，S和（-）-（亚甲基环丙基）甲醇（4）的R构型。那么（+）-6和（+）-4的构型分别是R，R和S。这些分配与环氧丙烷在环氧氯丙烷的环氧乙烷环上的初始攻击相符。还描述了改进的关键对映体中间体（R）-1a和（S）-1a的制备方法，对于合成核苷的抗病毒嘌呤亚甲基环丙烷类似物很重要。