(2S,3S,4S,5S)-2,5-bis<<(benzyloxy)carbonyl>amino>-3,4-dihydroxy-1,6-diphenylhexane | 143838-10-2

• 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: (2S,3S,4S,5S)-2,5-bis<<(benzyloxy)carbonyl>amino>-3,4-dihydroxy-1,6-diphenylhexane
• 英文别名: (2S,3S,4S,5S)-2,5-bis-(N-(((benzyl)oxy)carbonyl)amino)-3,4-dihydroxy-1,6-diphenylhexane；(2S,3S,4S,5S)-2,5-bis[[(benzyloxy)carbonyl]amino]-3,4-dihydroxy-1,6-diphenylhexane；benzyl N-[(2S,3S,4S,5S)-3,4-dihydroxy-1,6-diphenyl-5-(phenylmethoxycarbonylamino)hexan-2-yl]carbamate
• CAS: 143838-10-2
• 化学式: C₃₄H₃₆N₂O₆
• 分子量: 568.67
• InChiKey: VHZZMBIUMSGNBP-YDPTYEFTSA-N

物化性质

• 沸点：
  792.4±60.0 °C(Predicted)
• 密度：
  1.242±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  42
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  117
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,3S,4S,5S)-2,5-bis<<(benzyloxy)carbonyl>amino>-3,4-dihydroxy-1,6-diphenylhexane 在 barium dihydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 18.0h， 生成 (2S,3S,4S,5S)-2,5-diamino-1,6-diphenyl-3,4-hexanediol
  参考文献：
  名称：

  Stereocontrolled synthesis of C2-symmetric and pseudo-C2-symmetric diamino alcohols and diols for use in HIV protease inhibitors

  摘要：

  The stereocontrolled syntheses of dibenzyldiamino alcohol 1 and dibenzyldiamino diols 2-4, core units of potent C2-symmetric and pseudo-C2-symmetric inhibitors of HIV protease, are described, starting from phenylalanine. Stereoselective epoxidation of trans olefin 7, produced by S(N)2' displacement of an allylic mesylate, followed by regiospecific epoxide opening with lithium azide provided the azido alcohol 8 as the major product. Azide reduction and deprotection led to diamine 1. Protected diamino diols 15-17 were prepared expeditiously by intermolecular titanium- or vanadium-mediated pinacol coupling of protected phenylalaninal. Methods for the stereospecific interconversion of the major (3R,4R,5R,6S) isomer to the desired (3S,4R,5S,6S) isomer via intramolecular hydroxyl inversion are described.

  DOI：

  10.1021/jo00047a023
• 作为产物：
  描述：

  Z-L-苯丙氨醇 在 草酰氯 、 TEA 、 二甲基亚砜 作用下， 反应 0.5h， 生成 (2S,3S,4S,5S)-2,5-bis<<(benzyloxy)carbonyl>amino>-3,4-dihydroxy-1,6-diphenylhexane
  参考文献：
  名称：

  Stereocontrolled synthesis of C2-symmetric and pseudo-C2-symmetric diamino alcohols and diols for use in HIV protease inhibitors

  摘要：

  The stereocontrolled syntheses of dibenzyldiamino alcohol 1 and dibenzyldiamino diols 2-4, core units of potent C2-symmetric and pseudo-C2-symmetric inhibitors of HIV protease, are described, starting from phenylalanine. Stereoselective epoxidation of trans olefin 7, produced by S(N)2' displacement of an allylic mesylate, followed by regiospecific epoxide opening with lithium azide provided the azido alcohol 8 as the major product. Azide reduction and deprotection led to diamine 1. Protected diamino diols 15-17 were prepared expeditiously by intermolecular titanium- or vanadium-mediated pinacol coupling of protected phenylalaninal. Methods for the stereospecific interconversion of the major (3R,4R,5R,6S) isomer to the desired (3S,4R,5S,6S) isomer via intramolecular hydroxyl inversion are described.

  DOI：

  10.1021/jo00047a023

文献信息

• Method for synthesis of C2-symmetric diamino diol mediated by titanium complexes
  申请人：Wang Chun-Chih

  公开号：US20060287500A1

  公开（公告）日：2006-12-21

  A method for synthesis of C 2 -symmetric diamino diol mediated by titanium complexes is provided. A substituted-L-phenylalaninal undergoes pinacol coupling to yield the corresponding C 2 -symmetric (1S,2R,3R,4S)-1,4-diamino 2,3-diol in the presence of Cp 2 TiCl 2 /ZnCl 2 and zinc metal, mediated in good yield and highly selective. This titanium-catalyzed reaction yields diaminodiol, offering a convenient alternative method to the synthesis of C 2 -symmetric peptidic protease inhibitors. Consequently, the method allows to synthesize TL-3 via titanium complex in moderate yield.

  提供了一种通过钛配合物介导的C2对称二氨基二醇的合成方法。在Cp2TiCl2/ZnCl2和锌金属存在下，取代-L-苯丙氨酸经过缩醇偶联反应，产生相应的C2对称(1S,2R,3R,4S)-1,4-二氨基2,3-二醇，产率高且选择性强。这种钛催化反应产生了二氨基二醇，为合成C2对称肽酶抑制剂提供了便捷的替代方法。因此，该方法允许在中等产率下通过钛配合物合成TL-3。
• [EN] RETROVIRAL PROTEASE INHIBITING COMPOUNDS<br/>[FR] COMPOSES INHIBANT DES PROTEASES RETROVIRALES
  申请人：ABBOTT LABORATORIES

  公开号：WO1994014436A1

  公开（公告）日：1994-07-07

  (EN) A retroviral protease inhibiting compound of formula (A) is disclosed.(FR) L'invention se rapporte à un composé inhibant des protéases rétrovirales, qui est présenté par la formule (A).

  一种抑制反转录病毒蛋白酶的化合物公式（A）已被披露。(法语)本发明涉及一种通过公式（A）表示的抑制反转录病毒蛋白酶的化合物。
• [EN] PHARMACEUTICAL COMPOSITION OF HIV-PROTEASE INHIBITORS<br/>[FR] COMPOSITION PHARMACEUTIQUE D'INHIBITEURS DE LA PROTEASE DU VIH
  申请人：ABBOTT LABORATORIES

  公开号：WO1995007696A1

  公开（公告）日：1995-03-23

  (EN) A pharmaceutical composition is disclosed which comprises a solution of an HIV protease inhibiting compound in a pharmaceutically acceptable organic solvent comprising a pharmaceutically acceptable alcohol. The composition can optionally comprise a pharmaceutically acceptable acid or a combination of pharmaceutically acceptable acids. The solution can optionally be encapsulated in hard gelating capsule or soft elastic gelating capsules. The solution can optionally be granulated with a pharmaceutically acceptable granulating agent.(FR) Composition pharmaceutique comprenant une solution d'un composé inhibiteur de la protéase du VIH dans un solvant organique consistant en un alcool pharmacocompatible. Ladite composition qui peut comporter éventuellement un acide ou une combinaison d'acides pharmacocompatibles peut éventuellement être encapsulée dans des gélules de gélatine dure ou molle, ou mise sous forme de granulés à l'aide d'un agent de granulation pharmacocompatible .

  （中文翻译）揭示了一种制药组合物，它包括一种HIV蛋白酶抑制剂化合物的溶液，所述溶液在药学上可接受的有机溶剂中，包括药学上可接受的醇。该组合物可以选择性地包含药学上可接受的酸或药学上可接受的酸的组合。该溶液可以选择性地被封装在硬凝胶胶囊或软弹性凝胶胶囊中。该溶液可以选择性地与药学上可接受的造粒剂一起制成颗粒。
• [EN] PHARMACEUTICAL COMPOSITION<br/>[FR] COMPOSITION PHARMACEUTIQUE
  申请人：ABBOTT LABORATORIES

  公开号：WO1995009614A1

  公开（公告）日：1995-04-13

  (EN) A solid pharmaceutical composition is disclosed which comprises a pharmaceutically acceptable adsorbent or a mixture of pharmaceutically acceptable adsorbents to which is adsorbed a mixture of (1) a pharmaceutically acceptable organic solvent or a mixture of pharmaceutically accpetable organic solvents, (2) an HIV protease inhibiting compound and (3) one or more pharmaceutically acceptable acids. The solid composition can optionally be encapsulated in a hard gelatin capsule.(FR) L'invention concerne une composition pharmaceutique solide comprenenant un adsorbant pharmaceutiquement acceptable ou un mélange d'adsorbants pharmaceutiquement acceptables sur lequel a été adsorbé un mélange constitué de: (1) un solvant organique pharmaceutiquement acceptable ou un mélange de solvants organiques pharmaceutiquement acceptables, (2) un composé inhibant la protéase du VIH et (3) un ou plusieurs acides pharmaceutiquement acceptables. Ladite composition solide peut éventuellement être encapsulée dans une capsule de gélatine dure.

  一种固体药物组合物被揭示，其包括一种药学上可接受的吸附剂或药学上可接受的吸附剂混合物，该吸附剂或混合物吸附了一种混合物，该混合物由以下成分组成：(1)一种药学上可接受的有机溶剂或药学上可接受的有机溶剂混合物，(2)一种HIV蛋白酶抑制剂和(3)一种或多种药学上可接受的酸。该固体组合物可以选择性地被封装在硬明胶胶囊中。
• [EN] PHARMACEUTICAL COMPOSITIONS CONTAINING HIV PROTEASE INHIBITORS<br/>[FR] COMPOSITIONS PHARMACEUTIQUES CONTENANT DES INHIBITEURS DE PROTEASE DU VIH
  申请人：ABBOTT LABORATORIES

  公开号：WO1995020384A1

  公开（公告）日：1995-08-03

  (EN) A pharmaceutical composition is disclosed which comprises a solution of an HIV protease inhibiting compound in a pharmaceutically acceptable organic solvent comprising a mixture of (1): (a) a solvent selected from propylene glycol and polyethylene glycol or (b) a solvent selected from polyoxyethyleneglycerol triricinoleate, polyethylene glycol (40) hydrogenated castor oil, fractionated coconut oil, polyoxyethylene (20) sorbitan monooleate and 2-(2-ethoxyethoxy)ethanol or (c) a mixture thereof; and (2) ethanol or propylene glycol.(FR) La présente invention concerne une composition pharmaceutique comportant une solution d'un composé inhibiteur de protéase du VIH dans un solvant organique pharmaceutiquement acceptable. Ce solvant se compose, en premier lieu, soit (a) d'un solvant appartenant au groupe formé par le propylène glycol et le polyéthylène glycol, soit (b) d'un solvant appartenant au groupe se composant de triricinoléate de polyoxyéthylèneglycérol, polyéthylène glycol (40) hydrogéné - huile de ricin, huile de coprah fractionnée, polyoxyéthylène (20) mono-oléate de sorbitane et 2-(-éthoxyéthoxy)éthanol, soit enfin (c) d'un mélange de ces substances, et en second lieu, d'éthanol ou de propylène glycol.

  一种制药组合物被揭示，其包括一种HIV蛋白酶抑制剂化合物的溶液，该溶液在一种药学上可接受的有机溶剂中，该有机溶剂包括以下混合物：(1) (a) 从丙二醇和聚乙二醇中选择的溶剂或(b) 从聚氧乙烯甘油三蓖麻酸酯、聚乙二醇（40）氢化蓖麻油、分馏椰子油、聚氧乙烯（20）山梨醇单油酸酯和2-（2-乙氧基乙氧基）乙醇中选择的溶剂或(c) 其中的混合物；以及(2) 乙醇或丙二醇。