(4S,5R)-2,2-Dimethyl-4-(2-methylpropan-1-yl)-5-vinyl-1,3-dioxolane | 139727-17-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4S,5R)-2,2-Dimethyl-4-(2-methylpropan-1-yl)-5-vinyl-1,3-dioxolane
• 英文别名: (4S,5R)-2,2-Dimethyl-4-isobutyl-5-vinyl-1,3-dioxolane；(4R,5S)-4-ethenyl-2,2-dimethyl-5-(2-methylpropyl)-1,3-dioxolane
• CAS: 139727-17-6
• 化学式: C₁₁H₂₀O₂
• 分子量: 184.279
• InChiKey: MIMDHNWKNJCPAR-ZJUUUORDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4S,5R)-2,2-Dimethyl-4-(2-methylpropan-1-yl)-5-vinyl-1,3-dioxolane 在 镍 N-甲基吗啉 、 氢气 、 叔丁基锂 作用下， 以 四氢呋喃 、 甲醇 为溶剂， -90.0~25.0 ℃ 、405.3 kPa 条件下， 反应 27.08h， 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：

  (2S,3R)-1,2-epoxy-4-penten-3-ol 在 copper(l) iodide 、 magnesium sulfate 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 乙醚 、 丙酮 为溶剂， 反应 19.5h， 生成 (4S,5R)-2,2-Dimethyl-4-(2-methylpropan-1-yl)-5-vinyl-1,3-dioxolane
  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

文献信息

• Process for the preparation of a renin inhibiting compound
  申请人：Abbott Laboratories

  公开号：US05275950A1

  公开（公告）日：1994-01-04

  Intermediates and a process for their preparation are disclosed which are useful for the preparation of a renin inhibiting compound of the formula: ##STR1## wherein R is a nitrogen-containing heterocycle which is bonded via a nitrogen atom to the sulfonyl group, R.sub.6 is hydrogen, alkoxy, halogen or loweralkyl, R.sub.7 is loweralkyl having 2 to 7 carbon atoms, and R.sub.8 is loweralkyl, cycloalkyl, or aryl or a pharmaceutically acceptable acid addition salt thereof.

  本发明公开了一种中间体及其制备方法，可用于制备一种抑制肾素的化合物，其化学式为：##STR1## 其中R是通过氮原子与磺酰基结合的含氮杂环，R.sub.6是氢、烷氧基、卤素或低烷基，R.sub.7是具有2至7个碳原子的低烷基，R.sub.8是低烷基、环烷基或芳基，或其药学上可接受的酸加成盐。
• Renin inhibitors
  申请人：Abbott Laboratories

  公开号：US05284849A1

  公开（公告）日：1994-02-08

  A renin inhibiting compound of the formula: ##STR1## wherein R.sub.1 is 4-piperazinyl, 1-methyl-4-piperazinyl, 1-methyl-1-oxo-4-piperazinyl, 2-oxo-4-piperazinyl, 4-morpholinyl, 4-thiomorpholinyl or 1-methyl-4-homopiperazinyl; R.sub.2 is benzyl, 2-phenylethyl, 1-naphthylmethyl or 2-naphthylmethyl; R.sub.3 is 4-thiazolyl, 2-amino-4-thiazolyl, 2-thiazolyl, 5-thiazolyl, 1-pyrazolyl, 3-pyrazolyl, 1-imidazolyl, n-propyl, isopropyl, CH.sub.3 S--, or CH.sub.3 SCH.sub.2 --; R.sub.4 is isobutyl or cyclopropyl; R.sub.5 is hydrogen or loweralkyl; and X is CH.sub.2 or NH; or a pharmaceutically acceptable salt, ester or prodrug thereof; with the proviso that when X is NH and R.sub.3 is 2-amino-4-thiazolyl, then R.sub.4 is cyclopropyl.

  一种抑制肾素的化合物，其化学式为：##STR1## 其中R.sub.1为4-哌嗪基，1-甲基-4-哌嗪基，1-甲基-1-氧代-4-哌嗪基，2-氧代-4-哌嗪基，4-吗啉基，4-硫代吗啉基或1-甲基-4-杂环戊二氮基；R.sub.2为苄基，2-苯乙基，1-萘甲基或2-萘甲基；R.sub.3为4-噻唑基，2-氨基-4-噻唑基，2-噻唑基，5-噻唑基，1-吡唑基，3-吡唑基，1-咪唑基，正丙基，异丙基，CH.sub.3 S--或CH.sub.3 SCH.sub.2 --；R.sub.4为异丁基或环丙基；R.sub.5为氢或低碳基；X为CH.sub.2或NH；或其药学上可接受的盐，酯或前药；但是当X为NH且R.sub.3为2-氨基-4-噻唑基时，R.sub.4为环丙基。
• US5275950A
  申请人：——

  公开号：US5275950A

  公开（公告）日：1994-01-04
• US5284849A
  申请人：——

  公开号：US5284849A

  公开（公告）日：1994-02-08
• US5310740A
  申请人：——

  公开号：US5310740A

  公开（公告）日：1994-05-10