(1R,4S,5R,7S)-4-endo-methyl-7-endo-hydroxymethyl-6,8-dioxa-3-azabicyclo[3.2.1]octane | 250137-97-4

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: (1R,4S,5R,7S)-4-endo-methyl-7-endo-hydroxymethyl-6,8-dioxa-3-azabicyclo[3.2.1]octane
• 英文别名: [(1R,4S,5R,7S)-4-methyl-6,8-dioxa-3-azabicyclo[3.2.1]octan-7-yl]methanol
• CAS: 250137-97-4
• 化学式: C₇H₁₃NO₃
• 分子量: 159.185
• InChiKey: UXIASJADMVOIKV-BNHYGAARSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  50.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R,4S,5R,7S)-4-endo-methyl-7-endo-hydroxymethyl-6,8-dioxa-3-azabicyclo[3.2.1]octane 在 重铬酸吡啶 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 (1R,4S,5R,7R)-3-(9-fluorenylmethoxycarbonyl)-4-endo-methyl-6,8-dioxa-3-azabicyclo[3.2.1]octane-7-endo-carboxylic acid
  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
• 作为产物：
  描述：

  N-benzyl-N'-[(1S)-1-methyl-1-formyl]-(2R,3S)-2,3-di-isopropylidenetartramic acid methyl ester 在 palladium dihydroxide lithium aluminium tetrahydride 、 硫酸 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 14.33h， 生成 (1R,4S,5R,7S)-4-endo-methyl-7-endo-hydroxymethyl-6,8-dioxa-3-azabicyclo[3.2.1]octane
  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