1-[5-(1-amino-2-phenyl-ethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-2-phenyl-ethylamine | 136740-99-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[5-(1-amino-2-phenyl-ethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-2-phenyl-ethylamine
• 英文别名: 2S,5S-diamino-1,6-diphenyl-3,4-O-isopropylidenehexane-3R,4R-diol；(1S)-1-[(4R,5R)-5-[(1S)-1-amino-2-phenylethyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-phenylethanamine
• CAS: 136740-99-3
• 化学式: C₂₁H₂₈N₂O₂
• 分子量: 340.466
• InChiKey: DWYGCNIREGQVDY-VNTMZGSJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  70.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  氯甲酸苄酯 、 1-[5-(1-amino-2-phenyl-ethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-2-phenyl-ethylamine 在 盐酸 、 sodium hydroxide 作用下， 生成 (2S,3R,4R,5S)-2,5-bis<<(benzyloxy)carbonyl>amino>-3,4-dihydroxy-1,6-diphenylhexane
  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：

  (-)-2,3-O-亚异丙基-D-苏力糖醇 在 镍 草酰氯 、 氢气 、 magnesium sulfate 、 二甲基亚砜 、 苯基锂 、 三乙胺 作用下， 以 甲醇 为溶剂， -40.0~25.0 ℃ 、405.3 kPa 条件下， 反应 53.0h， 生成 1-[5-(1-amino-2-phenyl-ethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-2-phenyl-ethylamine
  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

• Inhibitors of retroviral proteases
  申请人：Abbott Laboratories

  公开号：US05712417A1

  公开（公告）日：1998-01-27

  The present invention relates to compounds of the formula I ##STR1## wherein A, Y, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, l, m and the corresponding radicals labeled with * are defined as stated in the description, a process for their preparation and their use for the inhibition of retroviral proteases.

  本发明涉及公式I的化合物，其中A，Y，R.sup.2，R.sup.3，R.sup.4，R.sup.5，R.sup.6，l，m和标有*的相应基团如说明书中所述，以及它们的制备方法和它们用于抑制逆转录病毒蛋白酶的用途。
• Inhibitoren retroviraler Proteasen
  申请人：HOECHST AKTIENGESELLSCHAFT

  公开号：EP0428849A2

  公开（公告）日：1991-05-29

  Die vorliegende Erfindung betrifft Verbindung der Formel I worin A, Y, R², R³, R⁴, R⁵, R⁶, l, m, sowie die entsprechenden mit * versehenen Reste wie in der Beschreibung angegeben definiert sind, ein Verfahren zu deren Herstellung, sowie ihre Verwendung zur Hemmung retroviraler Proteasen.

  本发明涉及一种式 I 的化合物 其中 A、Y、R²、R³、R⁴、R⁵、R⁶、l、m 和标有 * 的相应基团的定义、制备方法及其用于抑制逆转录病毒蛋白酶的用途。
• Expedient solid-phase synthesis of both symmetric and asymmetric diol libraries targeting aspartic proteases
  作者：Haibin Shi、Kai Liu、Wendy W.Y. Leong、Shao Q. Yao

  DOI：10.1016/j.bmcl.2009.03.041

  日期：2009.7

  C-2-symmetric diols have been shown to be highly potent against HIV-1 protease (PR). However, gaining access to these compounds has been hampered by the need of multistep solution-phase reactions which are often tedious and inefficient. In this Letter, we have disclosed a solid-phase strategy for rapid preparation of small molecule-based, symmetric and asymmetric diols as potential HIV-1 protease inhibitors. Upon biological screening, we found one of them, SYM-5, to be a potent and selective inhibitor (K-i = 400 nM) against HIV-1 protease. (C) 2009 Elsevier Ltd. All rights reserved.
• EP0538396A4
  申请人：——

  公开号：EP0538396A4

  公开（公告）日：1994-04-13
• INHIBITORS OF RETROVIRAL PROTEASES
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP0538396A1

  公开（公告）日：1993-04-28