(2S,3S)-2,3-dihydroxy-5-methyl-4-hexenoic acid acetonide | 147879-37-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,3S)-2,3-dihydroxy-5-methyl-4-hexenoic acid acetonide
• 英文别名: (4S,5S)-2,2-dimethyl-5-(2-methylprop-1-enyl)-1,3-dioxolane-4-carboxylic acid
• CAS: 147879-37-6
• 化学式: C₁₀H₁₆O₄
• 分子量: 200.235
• InChiKey: RCHRAOWLWIVEBT-YUMQZZPRSA-N

物化性质

• 沸点：
  313.1±42.0 °C(Predicted)
• 密度：
  1.153±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,3S)-2,3-dihydroxy-5-methyl-4-hexenoic acid acetonide 在 palladium on activated charcoal 、 镍 N-甲基吗啉 、 lithium aluminium tetrahydride 、 氢气 、 叔丁基锂 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 为溶剂， -90.0~25.0 ℃ 、405.3 kPa 条件下， 反应 53.58h， 生成 (2S,3R,4S)-2-[(tert-butyloxycarbonyl)amino]-1-cyclohexyl-3,4-dihydroxy-6-methylheptane
  参考文献：
  名称：

  Dipeptide isosteres. 1. Synthesis of dihydroxyethylene dipeptide isosteres via diastereoselective additions of alkyllithium reagents to N,N-dimethylhydrazones. Preparation of renin and HIV-1 protease inhibitor transition-state mimics

  摘要：

  The amino and diamino dihydroxyethylene dipeptide isosteres 19a,b and 23 are important intermediates for the preparation of inhibitors of human renin and HIV-1 protease, respectively. A general synthetic strategy was developed to access both dipeptide isosteres. The key step was a diastereoselective addition of an alkyllithium reagent to an aldehyde hydrazone. Thus, isosteres 19a and 19b were synthesized by addition of either benzyllithium or (cyclohexylmethyl)lithium to (4S,5R)-2,2-dimethyl-4-(2-methylpropan-1-yl)-5-formyl-1,3-dioxolane N,N-dimethylhydrazone (4) in diethyl ether at -10-degrees-C. The hydrazine addition product was reduced to the amine, and the acetonide protecting group was removed. The resulting amino diol was derivatized as either a N-Boc analogue or coupled to N-(tert-butyloxycarbonyl)-3-(thiazol-4-yl)alanine. The addition reactions were completely diastereoselective, affording only the chelation-controlled products (beta attack, S configuration at C(2)). Hydrazone 4 was prepared from either D-isoascorbic acid (1), divinyl carbinol (5), or chlorobenzene (9). Application of the hydrazone/alkyllithium reaction to the synthesis of the diamino dihydroxyethylene dipeptide isostere 23 was also achieved. Reaction of the bis-hydrazone 22 with benyllithium, followed by Raney nickel reduction of the hydrazine addition product, formation of the bis-benzyl carbamate, and deprotection of the acetonide with methanolic HCI gave the diamino dihydroxyethylene dipeptide isostere 23 in 36 % overall yield (four steps). Isostere 23 is an intermediate useful for the preparation Of C2 symmetric HIV-1 protease inhibitors.

  DOI：

  10.1021/jo00064a013
• 作为产物：
  描述：

  溴化异丙基(三苯基)磷 、 2,3-(isopropylidenedioxy)-4,4-dihydroxybutanic acid lactone 在 正丁基锂 作用下， 生成 (2S,3S)-2,3-dihydroxy-5-methyl-4-hexenoic acid acetonide
  参考文献：
  名称：

  Dipeptide isosteres. 1. Synthesis of dihydroxyethylene dipeptide isosteres via diastereoselective additions of alkyllithium reagents to N,N-dimethylhydrazones. Preparation of renin and HIV-1 protease inhibitor transition-state mimics

  摘要：

  The amino and diamino dihydroxyethylene dipeptide isosteres 19a,b and 23 are important intermediates for the preparation of inhibitors of human renin and HIV-1 protease, respectively. A general synthetic strategy was developed to access both dipeptide isosteres. The key step was a diastereoselective addition of an alkyllithium reagent to an aldehyde hydrazone. Thus, isosteres 19a and 19b were synthesized by addition of either benzyllithium or (cyclohexylmethyl)lithium to (4S,5R)-2,2-dimethyl-4-(2-methylpropan-1-yl)-5-formyl-1,3-dioxolane N,N-dimethylhydrazone (4) in diethyl ether at -10-degrees-C. The hydrazine addition product was reduced to the amine, and the acetonide protecting group was removed. The resulting amino diol was derivatized as either a N-Boc analogue or coupled to N-(tert-butyloxycarbonyl)-3-(thiazol-4-yl)alanine. The addition reactions were completely diastereoselective, affording only the chelation-controlled products (beta attack, S configuration at C(2)). Hydrazone 4 was prepared from either D-isoascorbic acid (1), divinyl carbinol (5), or chlorobenzene (9). Application of the hydrazone/alkyllithium reaction to the synthesis of the diamino dihydroxyethylene dipeptide isostere 23 was also achieved. Reaction of the bis-hydrazone 22 with benyllithium, followed by Raney nickel reduction of the hydrazine addition product, formation of the bis-benzyl carbamate, and deprotection of the acetonide with methanolic HCI gave the diamino dihydroxyethylene dipeptide isostere 23 in 36 % overall yield (four steps). Isostere 23 is an intermediate useful for the preparation Of C2 symmetric HIV-1 protease inhibitors.

  DOI：

  10.1021/jo00064a013