[(S)-1-((R)-2,2-Difluoro-1-(4-methoxy-phenylamino)-2-{(S)-2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butylcarbamoyl}-ethyl)-3-methyl-butyl]-carbamic acid tert-butyl ester | 109553-29-9

• 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: [(S)-1-((R)-2,2-Difluoro-1-(4-methoxy-phenylamino)-2-{(S)-2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butylcarbamoyl}-ethyl)-3-methyl-butyl]-carbamic acid tert-butyl ester
• CAS: 109553-29-9
• 化学式: C₃₂H₄₇F₂N₅O₅
• 分子量: 619.752
• InChiKey: OVSQEPRCAIYEOP-SSNGLDLMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.29
• 重原子数：
  44.0
• 可旋转键数：
  15.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  130.68
• 氢给体数：
  4.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  [(S)-1-((R)-2,2-Difluoro-1-(4-methoxy-phenylamino)-2-{(S)-2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butylcarbamoyl}-ethyl)-3-methyl-butyl]-carbamic acid tert-butyl ester 在 diethylphosphoryl cyanide 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 22.0h， 生成 (3R,4S)-4-{(S)-2-Amino-3-[1-(toluene-4-sulfonyl)-1H-imidazol-4-yl]-propionylamino}-2,2-difluoro-3-(4-methoxy-phenylamino)-6-methyl-heptanoic acid {(S)-2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butyl}-amide
  参考文献：
  名称：

  .alpha.,.alpha.-Difluoro-.beta.-aminodeoxystatine-containing renin-inhibitory peptides

  摘要：

  The preparations of sodium 4(S)-[(tert-butyloxycarbonyl)amino]-2,2-difluoro-3(S)- and -3(R)-[(4-methoxyphenyl)amino]-6-methylheptanoates (7a and 7b) from sodium 4(S)-[(tert-butyloxycarbonyl)amino]-2,2-difluoro-3(R)- and -3(S)-hydroxy-6-methylheptanoates (1a and 1b) are described. The key step involves the stereospecific intramolecular displacement via a Mitsunobu reaction for the conversion of a beta-hydroxy hydroxamate to a beta-lactam ring. Compounds 7a and 7b are useful as synthetic intermediates for the preparation of enzyme inhibitors that contain 3(S),4(S)- and 3(R),4(S)-diamino-2,2-difluoro-6-methylheptanoic acid inserts. Angiotensinogen analogues VII and VIII that contain these novel amino analogues of difluorostatine were shown to be inhibitors of the enzyme renin. The alpha,alpha-difluoro-beta-aminodeoxystatine-containing compounds were shown to be weaker inhibitors than the corresponding difluorostatine-containing congeners.

  DOI：

  10.1021/jm00393a026
• 作为产物：
  描述：

  N-(4-methoxyphenyl)-4(S)-<(tert-butyloxycarbonyl)amino>-2,2-difluoro-3(S)-hydroxy-6-methylheptanamide 在 sodium hydroxide 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 40.0h， 生成 [(S)-1-((R)-2,2-Difluoro-1-(4-methoxy-phenylamino)-2-{(S)-2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butylcarbamoyl}-ethyl)-3-methyl-butyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  .alpha.,.alpha.-Difluoro-.beta.-aminodeoxystatine-containing renin-inhibitory peptides

  摘要：

  The preparations of sodium 4(S)-[(tert-butyloxycarbonyl)amino]-2,2-difluoro-3(S)- and -3(R)-[(4-methoxyphenyl)amino]-6-methylheptanoates (7a and 7b) from sodium 4(S)-[(tert-butyloxycarbonyl)amino]-2,2-difluoro-3(R)- and -3(S)-hydroxy-6-methylheptanoates (1a and 1b) are described. The key step involves the stereospecific intramolecular displacement via a Mitsunobu reaction for the conversion of a beta-hydroxy hydroxamate to a beta-lactam ring. Compounds 7a and 7b are useful as synthetic intermediates for the preparation of enzyme inhibitors that contain 3(S),4(S)- and 3(R),4(S)-diamino-2,2-difluoro-6-methylheptanoic acid inserts. Angiotensinogen analogues VII and VIII that contain these novel amino analogues of difluorostatine were shown to be inhibitors of the enzyme renin. The alpha,alpha-difluoro-beta-aminodeoxystatine-containing compounds were shown to be weaker inhibitors than the corresponding difluorostatine-containing congeners.

  DOI：

  10.1021/jm00393a026