(4S,5R)-2,2-Dimethyl-4-(2-methylpropyl)-5-hydroxymethyl-1,3-dioxolane | 141364-54-7

• 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-methylpropyl)-5-hydroxymethyl-1,3-dioxolane
• 英文别名: (4S,5R)-2,2-Dimethyl-4-(2-methylpropan-1-yl)-5-(hydroxymethyl)-1,3-dioxolane；(4S,5R)-2,2-Dimethyl-4-(2-methylpropan-1-yl)-5-hydroxymethyl-1,3-dioxolane；[(4R,5S)-2,2-dimethyl-5-(2-methylpropyl)-1,3-dioxolan-4-yl]methanol
• CAS: 141364-54-7
• 化学式: C₁₀H₂₀O₃
• 分子量: 188.267
• InChiKey: MLUIQFVRBUSZRD-DTWKUNHWSA-N

物化性质

• 沸点：
  245.8±15.0 °C(Predicted)
• 密度：
  0.947±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4S,5R)-2,2-Dimethyl-4-(2-methylpropyl)-5-hydroxymethyl-1,3-dioxolane 在 RaNi N-甲基吗啉 、 盐酸 、 草酰氯 、 氢气 、 magnesium sulfate 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 为溶剂， -40.0~25.0 ℃ 、405.3 kPa 条件下， 反应 55.0h， 生成 (2S,3R,4S)-2-[(tert-butyloxycarbonyl)amino]-1-cyclohexyl-3,4-dihydroxy-6-methylheptane
  参考文献：
  名称：

  从D-异抗坏血酸实际合成二羟基乙烯二肽异甾体（（2S，3R，4S）2-[（叔丁氧基羰基）氨基] -1-环己基-3,4-二羟基-6-甲基庚烷

  摘要：

  将N-Boc二羟基二肽等排7和它的N-Boc 3-（噻唑-4-基）丙氨酰基衍生物8合成，无需纯化中间体，由（4S，5R）-2,2-二甲基-4-（2- -甲基丙基）-5-羟甲基-1,3-二氧戊环（3b）的总收率分别为24％和32％。醇3b可以很容易地从便宜且可商购的D-异抗坏血酸分四个步骤制备。该合成的特征在于将环己基甲基锂立体选择性地加成到（4S，5S）-2，2-二甲基-4-（2-甲基丙基）-5-甲酰基-1，3-二氧戊环（4）的二甲基中。

  DOI：

  10.1016/s0040-4039(00)91679-4
• 作为产物：
  描述：

  2,3-(isopropylidenedioxy)-4,4-dihydroxybutanic acid lactone 在 palladium on activated charcoal lithium aluminium tetrahydride 、 正丁基锂 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 为溶剂， -40.0~25.0 ℃ 、101.33 kPa 条件下， 反应 29.0h， 生成 (4S,5R)-2,2-Dimethyl-4-(2-methylpropyl)-5-hydroxymethyl-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

• A Practical Synthesis of the Dihydroxyethylene Dipeptide Isostere, (2S, 3R, 4S) 2-[(tert-Butyloxycarbonyl)amino]-1-cyclohexyl-3,4-dihydroxy-6-methylheptane, from D-Isoascorbic Acid
  作者：William R. Baker、Stephen L. Condon

  DOI：10.1016/s0040-4039(00)91679-4

  日期：1992.3

  )-5-hydroxymethyl-1,3-dioxolane (3b), in 24 and 32% overall yield, respectively. Alcohol 3b was readily prepared from inexpensive and commercially available D-isoascorbic acid in four steps. The synthesis featured a stereoselective addition of cyclohexylmethyllithium to the dimethyl hydrazone of (4S,5S)-2,2-dimethyl-4-(2-methylpropyl)-5-formyl-1,3-dioxolane (4).

  将N-Boc二羟基二肽等排7和它的N-Boc 3-（噻唑-4-基）丙氨酰基衍生物8合成，无需纯化中间体，由（4S，5R）-2,2-二甲基-4-（2- -甲基丙基）-5-羟甲基-1,3-二氧戊环（3b）的总收率分别为24％和32％。醇3b可以很容易地从便宜且可商购的D-异抗坏血酸分四个步骤制备。该合成的特征在于将环己基甲基锂立体选择性地加成到（4S，5S）-2，2-二甲基-4-（2-甲基丙基）-5-甲酰基-1，3-二氧戊环（4）的二甲基中。
• 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。
• US5275950A
  申请人：——

  公开号：US5275950A

  公开（公告）日：1994-01-04
• US5344990A
  申请人：——

  公开号：US5344990A

  公开（公告）日：1994-09-06
• 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
  作者：William R. Baker、Stephen L. Condon

  DOI：10.1021/jo00064a013

  日期：1993.6

  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.