(4S,5R)-3-(tert-butoxycarbonyl)-4-(cyclohexylmethyl)-2,2-dimethyloxazolidine-5-methanol | 143122-12-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (4S,5R)-3-(tert-butoxycarbonyl)-4-(cyclohexylmethyl)-2,2-dimethyloxazolidine-5-methanol
• 英文别名: tert-butyl (4S,5R)-4-(cyclohexylmethyl)-5-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 143122-12-7
• 化学式: C₁₈H₃₃NO₄
• 分子量: 327.464
• InChiKey: SAJCSOUXKZZRFD-GJZGRUSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4S,5R)-3-(tert-butoxycarbonyl)-4-(cyclohexylmethyl)-2,2-dimethyloxazolidine-5-methanol 在 N-甲基吗啉 、 盐酸 、 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.5h， 生成 tert-butyl N-[(2R)-1-[[(2S,3R)-1-cyclohexyl-3-hydroxy-4-(1H-1,2,4-triazol-5-ylsulfanyl)butan-2-yl]amino]-3-methylsulfanyl-1-oxopropan-2-yl]carbamate
  参考文献：
  名称：

  Renin inhibitors containing new P1-P1' dipeptide mimetics with heterocycles in P1'

  摘要：

  A series of renin inhibitors containing new P1-P1' dipeptide mimetics are presented The P1-P1' mimetics were obtained from (4S,5S)-3-(tert-butoxycarbonyl)-4-(cyclohexylmethyl)-5-[(omega-mesyloxy)alkyl]-2,2-dimethyloxazolidines 5b, 9, and 11b by nucleophilic substitution of the mesylate groups with the sodium salts of mercapto- and hydroxyheterocycles. Removal of the protecting groups and stepwise acylations with amino acid derivatives provided renin inhibitors with a length of a tripeptide. Replacement of P2 histidine by other amino acids maintained or enhanced renin inhibitory potency. By alteration of P3 phenylalanine, compounds with IC50 values in the nanomolar range and stability against chymotrypsin were obtained. Finally, the effect of the C-terminal heterocycle on the renin inhibition was studied. Compound XVII was examined in vivo for its hypotensive effects. In salt-depleted cynomolgus monkeys, XVII inhibited plasma renin activity and lowered blood pressure after oral administration of a dose of 10 mg/kg.

  DOI：

  10.1021/jm00097a010
• 作为产物：
  描述：

  (2R,3S)-3-tert-Butoxycarbonylamino-4-cyclohexyl-2-triisopropylsilanyloxy-butyric acid methyl ester 在 氢氟酸 、 4-甲基苯磺酸吡啶 、 二异丁基氢化铝 作用下， 以 吡啶 、 甲苯 、 乙腈 为溶剂， 反应 2.0h， 生成 (4S,5R)-3-(tert-butoxycarbonyl)-4-(cyclohexylmethyl)-2,2-dimethyloxazolidine-5-methanol
  参考文献：
  名称：

  β-内酰胺合成子法不对称合成二肽等排体的新方法

  摘要：

  通过由N -t-Boc-β-内酰胺4衍生的肟基6和甲酰恶唑啉13，已经开发出具有高对映体纯度的二肽等排体（例如，羟乙烯，二羟乙烯和羟乙胺等排体）的新型有效合成途径。

  DOI：

  10.1016/s0040-4039(97)10677-3

文献信息

• Renin inhibitors containing new P1-P1' dipeptide mimetics with heterocycles in P1'
  作者：Peter Raddatz、Alfred Jonczyk、Klaus Otto Minck、Friedrich Rippmann、Christine Schittenhelm、Claus Jochen Schmitges

  DOI：10.1021/jm00097a010

  日期：1992.9

  A series of renin inhibitors containing new P1-P1' dipeptide mimetics are presented The P1-P1' mimetics were obtained from (4S,5S)-3-(tert-butoxycarbonyl)-4-(cyclohexylmethyl)-5-[(omega-mesyloxy)alkyl]-2,2-dimethyloxazolidines 5b, 9, and 11b by nucleophilic substitution of the mesylate groups with the sodium salts of mercapto- and hydroxyheterocycles. Removal of the protecting groups and stepwise acylations with amino acid derivatives provided renin inhibitors with a length of a tripeptide. Replacement of P2 histidine by other amino acids maintained or enhanced renin inhibitory potency. By alteration of P3 phenylalanine, compounds with IC50 values in the nanomolar range and stability against chymotrypsin were obtained. Finally, the effect of the C-terminal heterocycle on the renin inhibition was studied. Compound XVII was examined in vivo for its hypotensive effects. In salt-depleted cynomolgus monkeys, XVII inhibited plasma renin activity and lowered blood pressure after oral administration of a dose of 10 mg/kg.
• New approaches to the asymmetric synthesis of dipeptide isosteres via β-Lactam Synthon Method
  作者：Iwao Ojima、Hong Wang、Tao Wang、Edward W. Ng

  DOI：10.1016/s0040-4039(97)10677-3

  日期：1998.2

  New and efficient synthetic routes to dipeptide isosteres with high enantiomeric purity, e.g., hydroxyethylene, dihydroxyethylene and hydroxyethylamine isosteres, have been developed via oxiranes 6 and formyloxazolines 13 derived from N-t-Boc-β-lactams 4.

  通过由N -t-Boc-β-内酰胺4衍生的肟基6和甲酰恶唑啉13，已经开发出具有高对映体纯度的二肽等排体（例如，羟乙烯，二羟乙烯和羟乙胺等排体）的新型有效合成途径。