TRANS-((1S,2S)-2-甲基环丙基)甲醇 | 21003-36-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: TRANS-((1S,2S)-2-甲基环丙基)甲醇
• 英文名称: trans-2-methylcyclopropanemethanol
• 英文别名: trans-(2-methylcyclopropyl)methanol；trans-2-methylcyclopropylcarbinol；[(1R,2R)-2-methylcyclopropyl]methanol
• CAS: 21003-36-1
• 化学式: C₅H₁₀O
• 分子量: 86.1338
• InChiKey: SHEINYPABNPRPM-UHNVWZDZSA-N

物化性质

• 沸点：
  60 °C(Press: 30 Torr)
• 密度：
  0.938±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  6
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 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：

  TRANS-((1S,2S)-2-甲基环丙基)甲醇 在 hexaammonium heptamolybdate tetrahydrate 、 偶氮二甲酸二异丙酯 、 双氧水 、 sodium hexamethyldisilazane 、 三苯基膦 、 pyridinium chlorochromate 、 calcium carbonate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 44.17h， 生成 (S)-6-((1E,3E,7E,9E)-10-((1R,2R)-2-methylcyclopropyl)deca-1,3,7,9-tetraen-1-yl)-5,6-dihydro-2H-pyran-2-one
  参考文献：
  名称：

  Coibacins A and B: Total Synthesis and Stereochemical Revision

  摘要：

  The interface between synthetic organic chemistry and natural products was explored in order to unravel the structure of coibacin A, a metabolite isolated from the marine cyanobacterium cf. Oscillatoria sp. that exhibits selective antileishmanial activity and potent anti-inflammatory properties. Our synthetic plan focused on a convergent strategy that allows rapid access to the desired target by coupling of three key fragments involving E-selective Wittig and modified Julia olefinations. CD measurements and comparative HPLC analyses of the natural product and four synthetic stereoisomers led to determination of its absolute configuration, thus correcting the original assignment at C-5 and unambiguously establishing those at C-16 and C-18. Additionally, we synthesized coibacin B on the basis of the assignment of configuration for coibacin A.

  DOI：

  10.1021/jo402339y
• 作为产物：
  描述：

  trans-1,2-dimethylcyclopropane radical 在 potassium phosphate buffer 、 乙二胺四乙酸 、 microsomal cytochrome P-450 、 potassium chloride 、 氧气 、 还原型辅酶II(NADPH)四钠盐 作用下， 反应 0.5h， 生成 TRANS-((1S,2S)-2-甲基环丙基)甲醇
  参考文献：
  名称：

  A radical clock investigation of microsomal cytochrome P-450 hydroxylation of hydrocarbons. Rate of oxygen rebound

  摘要：

  A number of alkyl-substituted cyclopropanes for which the rates of ring opening of the corresponding cyclopropylcarbinyl radicals have been determined (see preceding paper in this issue) have been used as substrates for hydroxylation by phenobarbital-induced, rat liver microsomal cytochrome P-450 at 37-degrees-C. Three of these compounds gave both ring-closed and ring-opened alcohols, thus allowing the rate constant, k(OH), for ''oxygen rebound'' onto the corresponding carbon-centered radicals to be determined. In particular, both trans- (1bH) and cis- (1cH) 1,2-dimethylcyclopropane gave 4-penten-2-ol (2bOH) and 2-methyl-3-buten-1-ol (3bOH) together with the corresponding trans- (1bOH) or cis-(1cOH) 2-methylcyclopropanemethanols. Of much greater importance, for both 1bH and 1cH the ratios of the yields of the secondary-to-primary ring-opened alcohols, i.e., [2bOH]/[3bOH], were the same, within experimental error as the ratio of the rates of ring opening of the corresponding trans- (1b.) and cis- (1c.) methylcyclopropylmethyl radicals in solution at 37-degrees-C. This indicates that when lb. and lc. are formed from their parent hydrocarbons by H-atom abstraction in the hydrophobic pocket of cytochrome P-450 they are not detectably constrained in their subsequent reactions by their unusual environment. From the ratio of the yields of the unrearranged alcohol to each of the rearranged alcohols we calculate k(OH) values of 1.5 and 1.6 x 10(10) s-1 for lbH as substrate and values of 1.9 and 1.8 x 10(10) s-1 for 1cH as substrate. Consistent with these values we have obtained k(OH) = 2.2 x 10(10) s-1 for bicyclo[2.1.0]pentane as substrate. Substrates such as methylcyclopropane and 1,1-dimethylcyclopropane, for which the corresponding cyclopropylmethyl radicals undergo relatively slow ring opening, yielded only the ring-closed alcohols on oxidation with cytochrome P-450. 1,1,2,2-Tetramethylcyclopropane gave only a trace of a ring-opened alcohol, corresponding to k(OH) = 2.5 x 10(11) s-1 for this substrate. Hexamethylcyclopropane gave no detectable ring-opened alcohol from which observation a limit for k(OH) > 5 X 10(11) s-1 can bc calculated. Possible explanations for the unexpected behavior of these last two, relatively bulky, substrates are discussed.

  DOI：

  10.1021/ja00015a025

文献信息

• Asymmetric Reductive Carbocyclization Using Engineered Ene Reductases
  作者：Kathrin Heckenbichler、Anna Schweiger、Lea Alexandra Brandner、Alexandra Binter、Marina Toplak、Peter Macheroux、Karl Gruber、Rolf Breinbauer

  DOI：10.1002/anie.201802962

  日期：2018.6.11

  bearing an electron‐withdrawing group, for example, a carbonyl group. This asymmetric reduction has been exploited for biocatalysis. Going beyond its canonical function, we show that members of this enzyme family can also catalyze the formation of C−C bonds. α,β‐Unsaturated aldehydes and ketones containing an additional electrophilic group undergo reductive cyclization. Mechanistically, the two‐electron‐reduced

  来自老黄酶 (OYE) 家族的烯还原酶可还原带有吸电子基团（例如羰基）的 α,β-不饱和化合物中的 C=C 双键。这种不对称还原已被用于生物催化。除了其典型功能之外，我们还发现该酶家族的成员还可以催化 C−C 键的形成。含有额外亲电基团的 α,β-不饱和醛和酮会发生还原环化。从机制上讲，双电子还原酶辅因子 FMN 传递氢化物以生成烯醇化物中间体，该中间体与内部亲电子试剂发生反应。用非质子 Phe 或 Trp 单位点取代关键的 Tyr 残基有利于环化反应而不是自然还原反应。新的转化使得对映选择性合成手性环丙烷的效率高达 >99% 。
• [EN] INHIBITORS OF TRPC6<br/>[FR] INHIBITEURS DE TRPC6
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2019161010A1

  公开（公告）日：2019-08-22

  The present invention relates to polycyclic compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R1 to R4, R7 to R10, Y and A are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本发明涉及公式(I)的多环化合物及其药用盐，其中R1至R4，R7至R10，Y和A如本文所定义。该发明还涉及包含这些化合物的药物组合物，使用这些化合物治疗各种疾病和疾病的方法，制备这些化合物的方法以及在这些过程中有用的中间体。
• Kinetic Enzymatic Resolution of Cyclopropane Derivatives
  作者：Jörg Pietruszka、Anja C. M. Rieche、Thorsten Wilhelm、Andreas Witt

  DOI：10.1002/adsc.200303137

  日期：2003.12

  enzymatic resolution of various cyclopropane derivatives was systematically investigated. The study focused on synthetically useful cyclopropylmethanols (e.g., 18a/j or 19a/j) as well as some rarely investigated cyclopropanols (e.g., 24/25 or 27). The combination of enantioselective catalytic or diastereoselective synthesis of enantiomerically enriched compounds with enzymatic approaches ultimately

  系统研究了各种环丙烷衍生物的动力学酶解。该研究集中于合成有用的环丙基甲醇（例如18a / j或19a / j）以及一些鲜有研究的环丙醇（例如24/25或27）。对映体富集化合物的对映选择性催化或非对映选择性合成与酶促方法的结合最终导致最方便的途径制备对映体纯的起始原料。再次证明了这一点，特别是对于环丙醇18a / j和19a / j的合成。成功进行研究的关键是严格建立一种分析工具，用于分析反应混合物的对映体组成。
• A novel synthesis of methylcyclopropanes
  作者：J. Nishimura、N. Kawabata、J. Furukawa

  DOI：10.1016/0040-4020(69)80006-2

  日期：1969.1

  prepared in 32–96% yield by the reaction of olefins with ethylidene iodide and diethylzinc. The reaction is electrophilic, and proceeds stereospecifically. In the case of the reaction with 1,2-disubstituted olefins, cis and trans olefins affords cyclopropane derivatives whose configurations with respect to the substituents from original olefins are cis and trans, respectively.

  通过烯烃与亚乙基碘和二乙基锌的反应，已经制备了几种甲基环丙烷，产率为32-96％。该反应是亲电的，并且立体定向地进行。在与1，2-二取代的烯烃反应的情况下，顺式和反式烯烃提供环丙烷衍生物，其相对于来自原始烯烃的取代基的构型分别为顺式和反式。
• Stereochemistry of the thermal isomerizations of (1R,2R)-1-[(E)-styryl]-2-methylcyclopropane to 3-phenyl-4-methylcyclopentenes
  作者：John E. Baldwin、Samuel Bonacorsi

  DOI：10.1021/ja00076a021

  日期：1993.11

  (1R,2R)-1-((E)-Styryl)-2-methylcyclopropane at 250 o C racemizes and isomerizes to 6-phenylhexa-1,4-(Z)-diene and to the four isomers of 3-phenyl-4-methylcyclopentene. From the measured rate constants for racemization and for structural isomerizations, and from information on the relative amounts of the four 3-phenyl-4-methylcyclopentenes as a function of time, the relative contributions of the four

  (1R,2R)-1-((E)-Styryl)-2-methylcyclopropane 在 250 o C 外消旋并异构化为 6-苯基六-1,4-(Z)-二烯和 3-苯基-的四种异构体4-甲基环戊烯。从外消旋化和结构异构化的测量速率常数，以及四种 3-苯基-4-甲基环戊烯的相对量随时间变化的信息，四种立体化学不同路径对这种乙烯基环丙烷重排的相对贡献是发现为 60% si、10% ar、19% sr 和 11% ai