N_α-benzoyl-D,L-asparagine benzyl ester | 368875-02-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N_α-benzoyl-D,L-asparagine benzyl ester
• 英文别名: Benzyl 4-amino-2-benzamido-4-oxobutanoate
• CAS: 368875-02-9
• 化学式: C₁₈H₁₈N₂O₄
• 分子量: 326.352
• InChiKey: CQQGPHOUEYLIAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  98.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N_α-benzoyl-D,L-asparagine benzyl ester 在 sodium hydroxide 、 Alcalase 2.4L from Bacillus sp 、 sodium chloride 作用下， 以 phosphate buffer 、 丙酮 为溶剂， 反应 17.9h， 以44%的产率得到N_α-benzoyl-D-asparagine benzyl ester
  参考文献：
  名称：

  Chemo-enzymatic preparation of chiral 3-aminopyrrolidine derivatives

  摘要：

  A new simple method for the enantioselective enzymatic hydrolysis of N-protected D-asparagine esters suitable for the use on the preparative scale is presented. Due to major obstacles observed under conventional reaction conditions-racemization of the retained ester and a strong enzyme inactivation-a comparatively low pH together with an organic co-solvent had to be employed. Under these conditions, nearly all tested proteases demonstrated good activity and excellent enantioselectivity giving access to the corresponding D-esters and L-asparagines in high optical purities (>95% ee) and good chemical yields (>40%). From the unnatural D-asparagine derivative, sequential cyclization, selective deprotection and reduction yielded efficiently benzyl protected (R)-3-aminopyrrolidine, a homo-chiral building block utilized in numerous drug candidates. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2003.10.118
• 作为产物：
  描述：

  N_α-benzoyl-D,L-asparagine 、 苯甲醇 在 氯化亚砜 作用下， 以33%的产率得到N_α-benzoyl-D,L-asparagine benzyl ester
  参考文献：
  名称：

  Chemo-enzymatic preparation of chiral 3-aminopyrrolidine derivatives

  摘要：

  A new simple method for the enantioselective enzymatic hydrolysis of N-protected D-asparagine esters suitable for the use on the preparative scale is presented. Due to major obstacles observed under conventional reaction conditions-racemization of the retained ester and a strong enzyme inactivation-a comparatively low pH together with an organic co-solvent had to be employed. Under these conditions, nearly all tested proteases demonstrated good activity and excellent enantioselectivity giving access to the corresponding D-esters and L-asparagines in high optical purities (>95% ee) and good chemical yields (>40%). From the unnatural D-asparagine derivative, sequential cyclization, selective deprotection and reduction yielded efficiently benzyl protected (R)-3-aminopyrrolidine, a homo-chiral building block utilized in numerous drug candidates. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2003.10.118

文献信息

• Chemo-enzymatic preparation of chiral 3-aminopyrrolidine derivatives
  作者：Hans Iding、Beat Wirz、Mark Rogers-Evans

  DOI：10.1016/j.tet.2003.10.118

  日期：2004.1

  A new simple method for the enantioselective enzymatic hydrolysis of N-protected D-asparagine esters suitable for the use on the preparative scale is presented. Due to major obstacles observed under conventional reaction conditions-racemization of the retained ester and a strong enzyme inactivation-a comparatively low pH together with an organic co-solvent had to be employed. Under these conditions, nearly all tested proteases demonstrated good activity and excellent enantioselectivity giving access to the corresponding D-esters and L-asparagines in high optical purities (>95% ee) and good chemical yields (>40%). From the unnatural D-asparagine derivative, sequential cyclization, selective deprotection and reduction yielded efficiently benzyl protected (R)-3-aminopyrrolidine, a homo-chiral building block utilized in numerous drug candidates. (C) 2003 Elsevier Ltd. All rights reserved.