methyl (1S,2R)-2-(((benzyloxy)carbonyl)amino)cyclobutane-1-carboxylate | 517913-98-3

• 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: methyl (1S,2R)-2-(((benzyloxy)carbonyl)amino)cyclobutane-1-carboxylate
• 英文别名: methyl (1S,2R)-2-(phenylmethoxycarbonylamino)cyclobutane-1-carboxylate
• CAS: 517913-98-3
• 化学式: C₁₄H₁₇NO₄
• 分子量: 263.293
• InChiKey: UOISHCCHGFCALE-NWDGAFQWSA-N

物化性质

• 沸点：
  401.9±44.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (1S,2R)-2-(((benzyloxy)carbonyl)amino)cyclobutane-1-carboxylate 在 锂硼氢 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 169.0h， 生成 ((1S,2R)-2-(((benzyloxy)carbonyl)amino)cyclobutyl)methyl (S)-1-(4-fluorophenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate
  参考文献：
  名称：

  [EN] PROGRANULIN MODULATORS AND METHODS OF USING THE SAME
  [FR] MODULATEURS DE PROGRANULINE ET LEURS MÉTHODES D'UTILISATION

  摘要：

  本文提供了调节前蛋白颗粒素并在前颞叶痴呆等与前蛋白颗粒素相关疾病中使用这些化合物的方法。

  公开号：

  WO2021127303A1
• 作为产物：
  描述：

  methyl hydrogen (-)-(1R,2S)-cyclobutane-1,2-dicarboxylate 在 氯甲酸乙酯 、 三乙胺 作用下， 以 丙酮 为溶剂， 反应 6.5h， 生成 methyl (1S,2R)-2-(((benzyloxy)carbonyl)amino)cyclobutane-1-carboxylate
  参考文献：
  名称：

  Enantioselective synthetic approaches to cyclopropane and cyclobutane β-amino acids: synthesis and structural study of a conformationally constrained β-dipeptide

  摘要：

  Synthetic approaches to carbocyclic compounds, namely cyclopropane and cyclobutane beta -amino acids, are presented. One of them is based on enzymatic desymmetrization of meso diesters, leading to the enantioselective production of cis-hemiesters, which afforded beta -amino acids through Curtius rearrangements. The enantiomeric excess for the cyclobutane derivatives was 91% whereas the cyclopropanes were obtained in 63% ee. According to another strategy, an enantiomerically pure cyclopropane trans-beta -amino acid, bearing a quaternary center, has been synthesized from a homochiral precursor easily available from D-glyceraldehyde. The preparation and structural investigation of the first synthesized cyclobutane containing dipeptide is also described. A hairpin-like conformation of this molecule in the solid state has been demonstrated by X-ray structural analysis, showing crystal packing induced by the presence of the rigid cyclobutane moiety and the formation of intermolecular hydrogen bonds. NMR experiments confirmed that these molecules also tend to produce aggregates in solution. On the contrary, theoretical calculations suggest that intramolecular interactions are important in the gas phase, as expected. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(00)00297-4

文献信息

• (+)- and (−)-2-Aminocyclobutane-1-carboxylic Acids and Their Incorporation into Highly Rigid β-Peptides:  Stereoselective Synthesis and a Structural Study
  作者：Sandra Izquierdo、Federico Rúa、Abdelouahid Sbai、Teodor Parella、Ángel Álvarez-Larena、Vicenç Branchadell、Rosa M. Ortuño

  DOI：10.1021/jo0510843

  日期：2005.9.1

  Several derivatives of (+)- and (−)-2-aminocyclobutane-1-carboxylic acid, 1, have been prepared through enantiodivergent synthetic sequences. The stereoselective synthesis of free amino acid (+)-1 has been achieved, and this product has been fully characterized for the first time. Stereocontrolled alternative synthetic methodologies have been developed for the preparation of bis(cyclobutane) β-dipeptides

  通过对映异构的合成序列已经制备了（+）-和（-）-2-氨基环丁烷-1-羧酸1的几种衍生物。立体选择性合成游离氨基酸（+）- 1已实现，并且此产品已首次全面表征。已经开发了立体控制的替代合成方法以高产率制备双（环丁烷）β-二肽。其中，已经合成了对映体和非对映体。还已经制备了由环丁烷残基和线性氨基酸的偶联产生的β，β-和β，δ-二聚体。已经显示出环丁烷环作为单体和二聚体中的结构促进单元的能力。NMR结构研究和DFT理论计算证明了强分子内分子的形成氢键产生顺式[4.2.0]辛烷结构单元，在溶液和气相中均赋予这些分子高刚性。还观察到了由围绕氨基甲酸酯NC（O）键旋转引起的顺式-反式构象平衡的贡献，反式是主要的构象体。在固态中，不存在该平衡，此外，存在分子间氢键。
• Stereoselectivity of Proline/Cyclobutane Amino Acid-Containing Peptide Organocatalysts for Asymmetric Aldol Additions: A Rationale
  作者：Ona Illa、Oriol Porcar-Tost、Carme Robledillo、Carlos Elvira、Pau Nolis、Oliver Reiser、Vicenç Branchadell、Rosa M. Ortuño

  DOI：10.1021/acs.joc.7b02745

  日期：2018.1.5

  computational calculations. The configuration of the aldol products is controlled by the proline chirality, and consequently, the R/S configuration of aldol products can be tuned by the use of either commercially available d- or l-proline. The enantioselectivity in the aldol reactions is reversed if the reactions are carried out in the presence of water or other protic solvents such as methanol. Spectroscopic

  已合成了几种α，β，α-或α，γ，α-三肽，它们由一个中央环丁烷β-或γ-氨基酸侧接两个d-或l-脯氨酸残基组成，并已作为不对称羟醛中的有机催化剂进行了测试补充。用α，γ，α-三肽已经获得了高产率和对映选择性，优于包含环丁烷β-氨基酸残基的肽。这可能是由于它们的高刚性，这阻碍了某些肽催化剂采用适当的活性构象。正如1 H NMR和计算结果所表明的，这种推论与处于基态的肽的主要构象有关。羟醛产物的构型受脯氨酸的手性控制，因此，R/小号的醛醇缩合产品的配置可以通过使用可商购的被调谐d或-升-脯氨酸。如果反应在水或其他质子溶剂如甲醇的存在下进行，则醛醇缩合反应中的对映选择性逆转。光谱和理论研究表明，这种影响不是催化剂构象变化的结果，而是由水分子以决定速率的过渡态参与而引起的，这种方式使得优先的亲核攻击指向相反的对映体醛面。
• Stereoselective Synthesis of All Stereoisomers of Orthogonally Protected Cyclobutane-1,2-diamine and Some Chemoselective Transformations
  作者：Marta Sans、Ona Illa、Rosa M. Ortuño

  DOI：10.1021/ol300689e

  日期：2012.5.18

  The four stereoisomers of protected cyclobutane-1,2-diamine have been prepared in an enantio- and diastereocontrolled manner through stereodivergent synthetic routes starting from a half-ester as a common chiral precursor. Orthogonal protection allows the chemoselective manipulation of both amino groups as shown in this work.
• Stereoselective synthesis of (−)-(1R,2S)-2-aminocyclobutane-1-carboxylic acid, a conformationally constrained β-amino acid
  作者：Marta Martı́n-Vilà、Cristina Minguillón、Rosa M. Ortuño

  DOI：10.1016/s0957-4166(98)00462-5

  日期：1998.12

  The title compound as well as some derivatives have been synthesized for the first time in optically active form by means of a chemoenzymatic transformation used to induce asymmetry in achiral precursors. The enantio- and diastereomeric purity has been determined by HPLC and NMR techniques. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Stereodivergent syntheses of the first bis(cyclobutane) β-dipeptides
  作者：Sandra Izquierdo、Marta Martı́n-Vilà、Albertina G. Moglioni、Vicenç Branchadell、Rosa M. Ortuño

  DOI：10.1016/s0957-4166(02)00652-3

  日期：2002.11

  The efficient synthesis of methyl 2-benzyloxycarbonylamino-(1S,2R)-cyclobutane-1-carboxylate starting from 2-methoxycarbonyl-(1R,2S)-cyclobutane-1-carboxylic acid is described. This beta-amino acid derivative is antipodal with respect to the (1R,2S)-compound that was previously synthesized in our laboratory from the same chiral hemi ester. In turn, these enantiomeric beta-amino acids have been self-condensed and coupled with one another to provide, respectively, enantiomeric and diastereomeric bis(cyclobutane) beta-dipeptides. These products are the first reported beta-amino acid oligomers containing two directly linked cyclobutane residues. (C) 2002 Elsevier Science Ltd. All rights reserved.