(Z)-(2R,3R,7S,8S)-2-Benzyl-8-tert-butoxycarbonylamino-9-(4-tert-butoxy-phenyl)-3,7-dihydroxy-non-4-enethioic acid S-benzyl ester | 479495-96-0

• 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: (Z)-(2R,3R,7S,8S)-2-Benzyl-8-tert-butoxycarbonylamino-9-(4-tert-butoxy-phenyl)-3,7-dihydroxy-non-4-enethioic acid S-benzyl ester
• CAS: 479495-96-0
• 化学式: C₃₈H₄₉NO₆S
• 分子量: 647.876
• InChiKey: TYKGPGQDDCAWDZ-MVAKCQCQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.29
• 重原子数：
  46.0
• 可旋转键数：
  14.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  105.09
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (Z)-(2R,3R,7S,8S)-2-Benzyl-8-tert-butoxycarbonylamino-9-(4-tert-butoxy-phenyl)-3,7-dihydroxy-non-4-enethioic acid S-benzyl ester 在 lithium hydroxide 、 双氧水 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以96%的产率得到(Z)-(2R,3R,7S,8S)-2-Benzyl-8-tert-butoxycarbonylamino-9-(4-tert-butoxy-phenyl)-3,7-dihydroxy-non-4-enoic acid
  参考文献：
  名称：

  High-Affinity Mu Opioid Receptor Ligands Discovered by the Screening of an Exhaustively Stereodiversified Library of 1,5-Enediols

  摘要：

  In this communication, we report the synthesis of an exhaustively stereodiversified library of 16 1,5-enediols (2) and the screening of these compounds for mu opioid receptor (MOR) binding. The stereochemical configuration of 2 strongly impacted the binding affinity, and (S,S,S,R)-2 exhibited a Ki of 8.8 nM for MOR, comparable to that of endomorphin-2 (Ki = 1.2 nM). Moreover, compounds 2 exhibited 5-86-fold selectivity for MOR over delta opioid receptor (DOR) and 16-150-fold selectivity for MOR over kappa opioid receptor (KOR). Additionally, analogues of 2 were synthesized which showed the importance of the trans olefin for receptor binding but that modifications of the C-terminal amino acid were well tolerated. Ligand 11 is noteworthy because it retains only one of the amide bonds present in 1, but binds MOR with an affinity of 10 nM and 110- and 600-fold selectivity for MOR over DOR and KOR. These results demonstrate the utility of stereochemical diversity in the discovery of bioactive small molecules.

  DOI：

  10.1021/ja027150p
• 作为产物：
  描述：

  2-benzyl-3-hydroxy-pent-4-enethioic S-benzyl ester 在 吡啶 、 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 氢氟酸 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 0.5h， 生成 (Z)-(2R,3R,7S,8S)-2-Benzyl-8-tert-butoxycarbonylamino-9-(4-tert-butoxy-phenyl)-3,7-dihydroxy-non-4-enethioic acid S-benzyl ester
  参考文献：
  名称：

  High-Affinity Mu Opioid Receptor Ligands Discovered by the Screening of an Exhaustively Stereodiversified Library of 1,5-Enediols

  摘要：

  In this communication, we report the synthesis of an exhaustively stereodiversified library of 16 1,5-enediols (2) and the screening of these compounds for mu opioid receptor (MOR) binding. The stereochemical configuration of 2 strongly impacted the binding affinity, and (S,S,S,R)-2 exhibited a Ki of 8.8 nM for MOR, comparable to that of endomorphin-2 (Ki = 1.2 nM). Moreover, compounds 2 exhibited 5-86-fold selectivity for MOR over delta opioid receptor (DOR) and 16-150-fold selectivity for MOR over kappa opioid receptor (KOR). Additionally, analogues of 2 were synthesized which showed the importance of the trans olefin for receptor binding but that modifications of the C-terminal amino acid were well tolerated. Ligand 11 is noteworthy because it retains only one of the amide bonds present in 1, but binds MOR with an affinity of 10 nM and 110- and 600-fold selectivity for MOR over DOR and KOR. These results demonstrate the utility of stereochemical diversity in the discovery of bioactive small molecules.

  DOI：

  10.1021/ja027150p