2-甲基-2-丙基[(2R)-1-苯基-3-丁烯-2-基]氨基甲酸酯 | 244092-76-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-甲基-2-丙基[(2R)-1-苯基-3-丁烯-2-基]氨基甲酸酯
• 中文别名: (R)1-苯基丁-3-烯-2-基氨基甲酸叔丁酯
• 英文名称: (R)-N-(tert-butoxycarbonyl)-3-amino-4-phenyl-1-butene
• 英文别名: (R)-2-(Boc-amino)-1-phenylbut-3-ene；(R)-tert-Butyl (1-phenylbut-3-en-2-yl)carbamate；tert-butyl N-[(2R)-1-phenylbut-3-en-2-yl]carbamate
• CAS: 244092-76-0
• 化学式: C₁₅H₂₁NO₂
• 分子量: 247.337
• InChiKey: WNAHEVXTGAEKIY-ZDUSSCGKSA-N

物化性质

• 熔点：
  67-68 °C
• 沸点：
  361.9±31.0 °C(Predicted)
• 密度：
  1.006±0.06 g/cm3(Predicted)
• 溶解度：
  溶于氯仿

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P264,P280,P302+P352,P305+P351+P338,P332+P313,P337+P313,P362
• 危险性描述：
  H315,H319

反应信息

• 作为反应物：
  描述：

  2-甲基-2-丙基[(2R)-1-苯基-3-丁烯-2-基]氨基甲酸酯 在 盐酸 、 N-乙酰-L-亮氨酸 、 potassium tert-butylate 、 三乙胺 作用下， 以 甲醇 、 丙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 129.0h， 生成 ((S)-1-benzylallyl)carbamic acid tert-butyl ester
  参考文献：
  名称：

  合成受N保护的α-氨基环氧化物的简便方法：HIV蛋白酶抑制剂的关键中间体

  摘要：

  描述了一种使用容易获得的烯丙胺合成2 R，3 S和2 S，3 S N -Boc苯丙氨酸环氧化物的简便方法。以前的方法使用多步从合成路线升-苯基丙氨酸，其中包括使用的米氯过苯甲酸（间- CPBA）和所期望的非对映体的纯化色谱法。可以通过对现有工艺进行重大改进来消除色谱柱纯化。通过替换m进一步增强了该过程-CPBA和ox​​one，一种对商业应用有利的环保试剂。所讨论的整个绿色过程涉及回收和再循环手性烯丙基胺的对映异构体，以及使用简单的经济方法合法分离环氧化物的非对映异构体。

  DOI：

  10.1021/op100174j
• 作为产物：
  描述：

  N-[(1R)-2-(甲氧基甲基氨基)-2-氧代-1-(苯基甲基)乙基]氨基甲酸1,1-二甲基乙基酯 在 lithium aluminium tetrahydride 作用下， 生成 2-甲基-2-丙基[(2R)-1-苯基-3-丁烯-2-基]氨基甲酸酯
  参考文献：
  名称：

  Triazole Ureas Act as Diacylglycerol Lipase Inhibitors and Prevent Fasting-Induced Refeeding

  摘要：

  Triazole ureas constitute a versatile class of irreversible inhibitors that target serine hydrolases in both cells and animal models. We have previously reported that triazole ureas can act as selective and CNS-active inhibitors for diacylglycerol lipases (DAGLs), enzymes responsible for the biosynthesis of 2-arachidonoylglycerol (2 -AG) that activates cannabinoid CB1 receptor. Here, we report the enantio- and diastereoselective synthesis and structure-activity relationship studies. We found that 2,4 -substituted triazole ureas with a biphenylmethanol group provided the most optimal scaffold. Introduction of a chiral ether substituent on the 5 -position of the piperidine ring provided ultrapotent inhibitor 38 (DH376) with picomolar activity. Compound 38 temporarily reduces fasting -induced refeeding of mice, thereby emulating the effect of cannabinoid' CB1-receptor inverse agonists. This was mirrored by 39 (DO34) but also by the negative control compound 40 (DO53) (which does not inhibit DAGL), which indicates the triazole ureas may affect the energy balance in mice through multiple molecular targets.

  DOI：

  10.1021/acs.jmedchem.6b01482

文献信息

• Diastereoselective epoxidation of allylically substituted alkenes using metalloporphyrin catalysts
  申请人：Che Chi-Ming

  公开号：US20050209470A1

  公开（公告）日：2005-09-22

  Diastereoselective epoxidation of allylically substituted alkenes using metalloporphyrins as catalyst provides high trans-selectivities (i.e., trans-:cis-epoxide ratio). A diversity of cycloalkenes bearing different allylic substituents are shown to be efficiently epoxidized to afford the corresponding trans-epoxides with excellent trans-selectivities (up to >98%) and good yields (up to 99%). Acyclic allylic alkenes bearing different allylic substituents are efficiently epoxidized to afford the corresponding erythro-epoxides with good erythro-selectivities. The metalloporphyrin-catalyzed reactions exhibit up to 20 times higher trans-selectivities than the conventional method using m-chloroperoxybenzoic acid as oxidant.

  使用金属卟啉作为催化剂的烯丙基取代烯烃的非对映选择性环氧化反应提供高选择性（即反式：顺式环氧化物比）。显示出带有不同烯丙基取代基的多样环烯烃能够有效地环氧化，产生相应的反式环氧化物，具有优异的反式选择性（高达>98%）和良好的产率（高达99%）。带有不同烯丙基取代基的无环烯丙基烯烃能够有效地环氧化，产生相应的顺式环氧化物，具有良好的顺式选择性。金属卟啉催化的反应显示出比使用m-氯过氧苯甲酸作为氧化剂的传统方法高达20倍的反式选择性。
• Metalloporphyrin-Catalyzed Diastereoselective Epoxidation of Allyl-Substituted Alkenes
  作者：Wing-Kei Chan、Man-Kin Wong、Chi-Ming Che

  DOI：10.1021/jo047733c

  日期：2005.5.1

  developed an efficient method for erythro-selective epoxidation of acyclic allyl-substituted alkenes, including allylic alcohols, amines, and esters. Up to 9:1 erythro selectivities for terminal allyllic alkenes could be achieved, which are significantly higher than that achieved using m-CPBA as an oxidant. In addition, the synthetic utilities of this epoxidation method were highlighted in stereoselective synthesis

  通过使用[Mn（2,6-Cl 2 TPP）Cl]（1）作为催化剂，Oxone / H 2 O 2作为氧化剂，我们开发了一种有效的方法，用于无环烯丙基取代的烯烃的赤型选择性环氧化，包括烯丙醇，胺和酯。末端烯丙基烯烃可达到9：1的赤型选择性，这明显高于使用m -CPBA作为氧化剂所达到的选择性。此外，这种环氧化方法的合成效用在关键的抗HIV药物中间体的立体选择性合成和糖基的环氧化中得到了强调。
• Synthesis of New (−)-Bestatin-Based Inhibitor Libraries Reveals a Novel Binding Mode in the S1 Pocket of the Essential Malaria M1 Metalloaminopeptidase
  作者：Geetha Velmourougane、Michael B. Harbut、Seema Dalal、Sheena McGowan、Christine A. Oellig、Nataline Meinhardt、James C. Whisstock、Michael Klemba、Doron C. Greenbaum

  DOI：10.1021/jm101227t

  日期：2011.3.24

  The malarial PfA-M1 metalloaminopeptidase is considered a putative drug target. The natural product dipeptide mimetic, bestatin, is a potent inhibitor of PfA-M1. Herein we present a new, efficient, and high-yielding protocol for the synthesis of bestatin derivatives from natural and unnatural N-Boc-D-amino acids. A diverse library of bestatin derivatives was synthesized with variants at the side chain of either the alpha-hydroxy-beta-amino acid (P1) or the adjacent natural a-amino add (P1'). Surprisingly, we found that extended aromatic side chains at the P1 position resulted in potent inhibition against PfA-M1. To understand these data, we determined the X-ray cocrystal structures of PfA-M1 with two derivatives having either a Tyr(OMe) 15 or Tyr(OBz1) 16 at the 131 position and observed substantial inhibitor-induced rearrangement of the primary loop within the PEA-M1 pocket that interacts with the PI side chain. Our data provide important insights for the rational design of more potent and selective inhibitors of this enzyme that may eventually lead to new therapies for malaria.
• Stereochemical Analysis of (Hydroxyethyl)urea Peptidomimetic Inhibitors of γ-Secretase
  作者：Pancham Bakshi、Michael S. Wolfe

  DOI：10.1021/jm049566e

  日期：2004.12.1

  (Hydroxyethyl)urea peptidomimetics systematically altered at positions P2-P3' with hydrophobic D-amino acids were synthesized. An all D-amino acid containing analogue was identified that effectively blocked gamma-secretase activity in a cell-free system (IC50 = 30 nM). Systematic alteration of the stereocenters of a potent compound revealed interdependence between the various positions. Although typically less potent than their L-peptidomimetic counterparts. selected all D-amino acid containing analogues were equipotent. to their counterparts in a cell-based assay when incubated for extended times.
• Polymer-Supported Ruthenium Porphyrins:  Versatile and Robust Epoxidation Catalysts with Unusual Selectivity
  作者：Xiao-Qi Yu、Jie-Sheng Huang、Wing-Yiu Yu、Chi-Ming Che

  DOI：10.1021/ja000461k

  日期：2000.6.1

  Carbonyl ruthenium(II) 5,10,15-tris(4-R-phenyl)-20-(4-hydroxyphenyl)porphyrins (R = Cl, Me) covalently attached Co Merrifield's peptide resin were prepared. The catalyst with R = Cl was found to efficiently catalyze Cl(2)pyNO epoxidation of a wide variety of alkenes, including aromatic and aliphatic terminal alkenes, cis- and trans-stilbene, cyclohexene and cyclooctene, alpha,beta-unsaturated ketones, conjugated enyne, glycal, and protected alpha-amino alkene. Unusual selectivities were observed for the epoxidations of 1,5-cyclooctadiene,cis-1-phenyl-3-penten-1-yne (9), 3,4,6-tri-O-acetyl-D-glucal (11), and 2-(Boc-amino)-1-phenylbut-3-ene (13), which feature a complete bisepoxide selectivity (1,5-cyclooctadiene), unprecedentedly high cis:trans ratio (9), and complete diastereoselectivity (11 and 13). The new heterogenized metalloporphyrin epoxidation catalysts are of high stability and reusability.