methyl (1R,5S,7R)-3-benzyl-2-oxo-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-exo-carboxylate | 250137-79-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧氮杂卓类
• 英文名称: methyl (1R,5S,7R)-3-benzyl-2-oxo-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-exo-carboxylate
• 英文别名: (1R,5S,7R)-3-benzyl-2-oxo-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-exo-carboxylic acid methyl ester；methyl 3-benzyl-2-oxo-(1R,5S,7R)-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-exo-carboxylate；methyl (1R,5S,7R)-3-benzyl-2-oxo-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-carboxylate
• CAS: 250137-79-2
• 化学式: C₁₄H₁₅NO₅
• 分子量: 277.277
• InChiKey: WYTLOBQYXILRKB-QJPTWQEYSA-N

物化性质

• 熔点：
  82 °C
• 沸点：
  453.7±45.0 °C(Predicted)
• 密度：
  1.329±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (1R,5S,7R)-3-benzyl-2-oxo-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-exo-carboxylate 在 dimethyl sulfide borane 、 sodium hydroxide 、 水 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 18.0h， 生成 methyl (1S,5S,7R)-3-benzyl-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-exo-carboxylate
  参考文献：
  名称：

  [EN] PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF DISEASES RELATED TO NEUROTROPHINES
  [FR] COMPOSITIONS PHARMACEUTIQUES POUR LE TRAITEMENT DE MALADIES ASSOCIEES AUX NEUROTROPHINES

  摘要：

  本发明涉及包含作为活性化合物的3-aza-bicyclo[3.2.1]辛烷衍生物的药物制剂，其通用式为(I)，以及其通用式为(II)和(III)的二聚体，作为人类神经营养因子的激动剂。因此，通式(I)、(II)和(III)的这些化合物对于治疗神经营养因子功能缺陷相关的疾病非常有用，尤其是神经生长因子（NGF）缺陷，例如中枢神经系统（CNS）的神经退行性疾病、由于NGF生物可用性降低而导致的获得性免疫缺陷，或者在其中新生血管生成过程的刺激是方便的病态条件。

  公开号：

  WO2004000324A1
• 作为产物：
  描述：

  (4R,5R)-5-(methoxycarbonyl)-2,2-dimethyl-1,3-dioxolane-4-carboxylic acid 在 硫酸 、 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 2.25h， 生成 methyl (1R,5S,7R)-3-benzyl-2-oxo-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-exo-carboxylate
  参考文献：
  名称：

  Synthesis and Reactivity of Bicycles Derived from Tartaric Acid and α-Amino Acids:  A Novel Class of Conformationally Constrained Dipeptide Isosteres Based upon Enantiopure 3-Aza-6,8-dioxabicyclo[3.2.1]octane-7-carboxylic Acid

  摘要：

  3-Aza-6,8-dioxabicyclo[3.2.1]octane-7-carboxylic acids (named BTAa) derived from (R,R), (S,S)-, or meso-tartaric acid and natural (L), unnatural (D), or unusual alpha-amino acids are described as conformationally constrained dipeptide isosteres. The general strategy developed for their preparation has required the transformation of the amino acids into the corresponding N-benzylamino alcohols, followed by the PyBroP-promoted condensation with the monomethyl ester of the suitable 2,3-di-O-isopropylidenetartaric acid. Oxidation of the hydroxy group to aldheyde and subsequent acid-catalyzed trans-acetalization with the two hydroxy groups of the tartaric acid moiety provided 3-aza-2-oxo-6,8-dioxabicyclo [3.2.1] octane-7-carboxylic acid methyl esters [named BTAa(O)] in good yield and, in most cases, as single enantiopure diastereoisomers. This strategy has been applied to the preparation of BTAa(O) starting from (R,R)-, (S,S)-, or meso-tartaric acid and glycine, L- and D-phenylalanine, L- and D-alanine, and (+/-)-phenylglycine. In the cases of glycine, L- and D-phenylalanine, and L- and D-alanine, the selective reduction by BH3. DMS of the amide group succeeding to the cyclization step, or the reduction of both amide and ester functions followed by reoxidation of the hydroxy to carboxylic group, provided in good yield the 3-aza-3-benzyl-6,8-dioxabicyclo[3.2.1]-octane-7-carboxylic acids (or their methyl ester) BTAa, having the side chain of the amino acid precursors at position 4. The stability and rigidity of the bicyclic skeleton, the complete control of all the stereocenters, the possibility of introducing the side chains of L- or D-amino acids, and the demonstrated compatibility with the conditions required for solid-phase peptide synthesis make the BTAa compounds potential dipeptide isosteres useful for the synthesis of modified peptides.

  DOI：

  10.1021/jo9904967

文献信息

• Design and synthesis of bicyclic acetals as Beta Secretase (BACE1) inhibitors
  作者：Riccardo Innocenti、Elena Lenci、Gloria Menchi、Alberto Pupi、Andrea Trabocchi

  DOI：10.1016/j.bmc.2017.03.030

  日期：2017.10

  Taking advantage of the structural similarity between aspartic proteases, small-molecule peptidomimetic inhibitors that already showed activity towards Secreted Aspartic Protease 2 as anti-Candida agents and HIV protease inhibitors were exploited as potential BACE1 inhibitors. A focused library of 6,8-dioxa-3-azabicyclo[3.2.1]-octane peptidomimetic scaffolds was synthesized and assayed towards BACE1

  利用天冬氨酸蛋白酶之间的结构相似性，已利用小分子拟肽抑制剂作为潜在的BACE1抑制剂，该抑制剂已显示出对分泌天冬氨酸蛋白酶2的活性，并作为抗Candida药剂和HIV蛋白酶抑制剂。合成了一个聚焦的6,8-二氧杂-3-氮杂双环[3.2.1]-辛烷拟肽支架文库，并针对BACE1酶进行了分析，从而鉴定出了具有低微摩尔范围IC50的含硫内酰胺命中化合物，并且证实双环缩醛部分是与催化天冬氨酸残基相互作用的潜在过渡态类似物。
• Diastereoselective Synthesis of Highly Constrained Spiro-β-Lactams by the Staudinger Reaction Using an Unsymmetrical Bicyclic Ketene
  作者：Andrea Trabocchi、Claudia Lalli、Francesco Guarna、Antonio Guarna

  DOI：10.1002/ejoc.200700260

  日期：2007.9

  A rigid bicyclic ketene was used to generate highly constrained polycyclic spiro-β-lactams through the Staudinger reaction. Depending on the imine component, high diastereoselectivity was observed in the process, leading to mainly the cis diastereoisomer in the case of aromatic imines. This results from an anti addition of the imine to the ketene, followed by a conrotatory ring closure in which the

  刚性双环烯酮用于通过施陶丁格反应生成高度受限的多环螺-β-内酰胺。取决于亚胺组分，在该过程中观察到高非对映选择性，在芳族亚胺的情况下主要导致顺式非对映异构体。这是由于亚胺与乙烯酮的反加成，随后发生旋转闭环，其中支架的 6 位杂原子由于扭矩电子效应向外旋转。 (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 魏因海姆，德国，2007）
• Oligomers of Enantiopure Bicyclic γ/δ-Amino Acids (BTAa). 1. Synthesis and Conformational Analysis of 3-Aza-6,8-dioxabicyclo[3.2.1]octane-7-carboxylic Acid Oligomers (PolyBTG)
  作者：Fabrizio Machetti、Alessandro Ferrali、Gloria Menchi、Ernesto G. Occhiato、Antonio Guarna

  DOI：10.1021/ol006548s

  日期：2000.12.1

  A series of dimeric through pentameric oligomers of a bicyclic gamma/delta -amino acid (BTG) were synthesized using peptide coupling methods in solution with PyBroP or HATU. The analysis of H-1 NMR and Co spectra suggests that these oligomers could have a partially ordered structure in alcohol solutions.