tert-butyl (1S,2S,4S)-4-azido-1-benzyl-2-hydroxy-5-phenylpentylcarbamate | 482648-05-5

• 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: tert-butyl (1S,2S,4S)-4-azido-1-benzyl-2-hydroxy-5-phenylpentylcarbamate
• 英文别名: tert-butyl N-[(2S,3S,5S)-5-azido-3-hydroxy-1,6-diphenylhexan-2-yl]carbamate
• CAS: 482648-05-5
• 化学式: C₂₃H₃₀N₄O₃
• 分子量: 410.516
• InChiKey: DKBUVLKLWMBCFN-ACRUOGEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  72.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (1S,2S,4S)-4-azido-1-benzyl-2-hydroxy-5-phenylpentylcarbamate 在 palladium on activated charcoal 氢气 、 三氟乙酸 作用下， 以 水 为溶剂， 生成 SSS-2,5-diamino-1,6-diphenyl-3-hexanol
  参考文献：
  名称：

  Small hydroxyethylene-based peptidomimetics inhibiting both HIV-1 and C. albicans aspartic proteases

  摘要：

  We have extended a highly flexible method for rapidly assembling aspartic protease inhibitors to produce symmetric and asymmetric monohydroxyethylene peptidomimetics. This method is based on the prior synthesis of the central non-cleavable peptide-bond isostere [NH2-P(1psi)P1'-NH2; psi = hydroxyethylene isostere, HNCH(Bz)CHOHCH2CH(Bz)NH], with the possibility of accurately controlling its stereochemistry (S,S,S or S,R,S), and subsequently adding appropriate flanking units, chosen from commercially available amino acids, aromatic carboxylic acids, or phenoxyacetic acid (Poa) derivatives. The method was used to make asymmetric inhibitors of general formula Kyn-Xaa-PhepsiPhe-dmPoa, (Kyn = kynurenic acid, Xaa - Val, Thr or D-thienylglycine, M-r = 716-754) and symmetric inhibitors of formula xPoa-PhepsiPhe-xPoa (xPoa = Poa or dimethyl-, hydroxy-, formyl- or acetyl-Poa. Poa, M-r = 553-609). with logP(o/w). values ranging from 4.1 to 7.6. Inhibition of HIV-PR did not depend on the stereochemistry of the hydroxyl group, while it depended markedly on the substituents present on the Poa residues, with dmPoa being preferred over Poa or its more hydrophilic derivatives. Conversely, inhibition of Candida albicans Sap2 was higher for the S,S,S epimers, and Poa or its hydrophilic derivatives were preferred over dmPoa. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.08.004
• 作为产物：
  描述：

  N-叔丁氧羰基-L-苯丙氨酸甲酯 在 sodium tetrahydroborate 、 正丁基锂 、 sodium azide 、 18-冠醚-6 、 sodium hydride 、 potassium carbonate 、 caesium carbonate 、 甲基磺酰氯 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 红铝 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 1,2-二氯乙烷 为溶剂， 生成 tert-butyl (1S,2S,4S)-4-azido-1-benzyl-2-hydroxy-5-phenylpentylcarbamate
  参考文献：
  名称：

  Small hydroxyethylene-based peptidomimetics inhibiting both HIV-1 and C. albicans aspartic proteases

  摘要：

  We have extended a highly flexible method for rapidly assembling aspartic protease inhibitors to produce symmetric and asymmetric monohydroxyethylene peptidomimetics. This method is based on the prior synthesis of the central non-cleavable peptide-bond isostere [NH2-P(1psi)P1'-NH2; psi = hydroxyethylene isostere, HNCH(Bz)CHOHCH2CH(Bz)NH], with the possibility of accurately controlling its stereochemistry (S,S,S or S,R,S), and subsequently adding appropriate flanking units, chosen from commercially available amino acids, aromatic carboxylic acids, or phenoxyacetic acid (Poa) derivatives. The method was used to make asymmetric inhibitors of general formula Kyn-Xaa-PhepsiPhe-dmPoa, (Kyn = kynurenic acid, Xaa - Val, Thr or D-thienylglycine, M-r = 716-754) and symmetric inhibitors of formula xPoa-PhepsiPhe-xPoa (xPoa = Poa or dimethyl-, hydroxy-, formyl- or acetyl-Poa. Poa, M-r = 553-609). with logP(o/w). values ranging from 4.1 to 7.6. Inhibition of HIV-PR did not depend on the stereochemistry of the hydroxyl group, while it depended markedly on the substituents present on the Poa residues, with dmPoa being preferred over Poa or its more hydrophilic derivatives. Conversely, inhibition of Candida albicans Sap2 was higher for the S,S,S epimers, and Poa or its hydrophilic derivatives were preferred over dmPoa. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.08.004

文献信息

• Epoxyalcohol Route to Hydroxyethylene Dipeptide Isosteres. Stereodivergent Synthesis of the Diamino Alcohol Core of Ritonavir and Its C-2 Epimer
  作者：Fabio Benedetti、Federico Berti、Stefano Norbedo

  DOI：10.1021/jo025616g

  日期：2002.11.1

  A stereoselective synthesis of hydroxyethylene dipeptide isosteres based on the 1,4-diamino-2-hydroxybutane structure is described. Horner-Emmons olefination of phosphonates derived from alpha-amino acids, stereoselective reduction of the resulting enones to allylic alcohols, and syn epoxidation of the latter lead to enantiomerically pure 1-amino-2-hydroxy-3,4-epoxybutanes, key intermediates in the

  描述了基于1，4-二氨基-2-羟基丁烷结构的羟乙烯二肽等排体的立体选择性合成。衍生自α-氨基酸的膦酸酯的Horner-Emmons烯化，立体选择性地将所得烯酮还原为烯丙醇，以及后者的顺环氧化反应生成对映体纯的1-氨基-2-羟基-3,4-环氧丁烷综合。环氧醇与Red-Al的还原裂解以高度区域选择性的方式进行，得到1-氨基-2,4-二羟基丁烷，通过对第二个2-羟基的选择性保护，环化为1,3-恶唑烷酮，进一步精制4-羟基。两个C-2差向异构体，4-氨基-2- hydroxybutanes是通过用于环化的条件适当选择使用。该方法通过一系列六个羟乙烯二肽等位基因的合成得到证明，包括有效的HIV蛋白酶抑制剂利托那韦18的二氨基醇核心及其C-2差向异构体11a。
• Stereoselective Hydroazidation of Amino Enones:  Synthesis of the Ritonavir/Lopinavir Core
  作者：Ilaria Adamo、Fabio Benedetti、Federico Berti、Pietro Campaner

  DOI：10.1021/ol0524104

  日期：2006.1.1

  acid was found to proceed with high stereoselectivity in favor of the syn product. The stereoselectivity is controlled by the configuration of the enone and syn/anti ratios up to 7:1 were obtained with secondary and tertiary amines at low temperature. By this route the diamino alcohol core of HIV-PR inhibitors ritonavir and lopinavir was synthesized in 37% yield from phenylalanine.

  [反应：见正文]发现α'-氨基α，β-不饱和酮与原位生成的氢azo酸的碱催化加氢叠氮反应以高立体选择性进行，有利于合成产物。立体选择性由烯酮的构型控制，在低温下用仲胺和叔胺可获得高达7：1的顺/反比。通过这种途径，从苯丙氨酸以37％的产率合成了HIV-PR抑制剂利托那韦和洛匹那韦的二氨基醇核心。
• Epoxyalcohol route to hydroxyethylene dipeptide isosteres: a new synthesis of the diaminoalcohol core of HIV-protease inhibitor ABT-538 (Ritonavir)
  作者：Fabio Benedetti、Stefano Norbedo

  DOI：10.1039/b005804l

  日期：——

  A stereoselective synthesis of the diaminoalcohol core of Ritonavir illustrates a novel approach to hydroxyethylene dipeptide isosteres, based on the regioselective reduction of amino acid-derived epoxyalcohols.

  利托那韦二氨基醇核心的立体选择性合成说明了一种基于氨基酸衍生的环氧醇的区域选择性还原的羟基乙烯二肽等排体的新方法。
• Small hydroxyethylene-based peptidomimetics inhibiting both HIV-1 and C. albicans aspartic proteases
  作者：Alessandro Tossi、Fabio Benedetti、Stefano Norbedo、Damiano Skrbec、Federico Berti、Domenico Romeo

  DOI：10.1016/j.bmc.2003.08.004

  日期：2003.11

  We have extended a highly flexible method for rapidly assembling aspartic protease inhibitors to produce symmetric and asymmetric monohydroxyethylene peptidomimetics. This method is based on the prior synthesis of the central non-cleavable peptide-bond isostere [NH2-P(1psi)P1'-NH2; psi = hydroxyethylene isostere, HNCH(Bz)CHOHCH2CH(Bz)NH], with the possibility of accurately controlling its stereochemistry (S,S,S or S,R,S), and subsequently adding appropriate flanking units, chosen from commercially available amino acids, aromatic carboxylic acids, or phenoxyacetic acid (Poa) derivatives. The method was used to make asymmetric inhibitors of general formula Kyn-Xaa-PhepsiPhe-dmPoa, (Kyn = kynurenic acid, Xaa - Val, Thr or D-thienylglycine, M-r = 716-754) and symmetric inhibitors of formula xPoa-PhepsiPhe-xPoa (xPoa = Poa or dimethyl-, hydroxy-, formyl- or acetyl-Poa. Poa, M-r = 553-609). with logP(o/w). values ranging from 4.1 to 7.6. Inhibition of HIV-PR did not depend on the stereochemistry of the hydroxyl group, while it depended markedly on the substituents present on the Poa residues, with dmPoa being preferred over Poa or its more hydrophilic derivatives. Conversely, inhibition of Candida albicans Sap2 was higher for the S,S,S epimers, and Poa or its hydrophilic derivatives were preferred over dmPoa. (C) 2003 Elsevier Ltd. All rights reserved.