tert-butyl (1S,2R,4S)-4-amino-1-benzyl-2-hydroxy-5-phenylpentylcarbamate | 331767-03-4

• 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,2R,4S)-4-amino-1-benzyl-2-hydroxy-5-phenylpentylcarbamate
• 英文别名: tert-butyl N-[(1S,2R,4S)-4-amino-1-benzyl-2-hydroxy-5-phenyl-pentyl]carbamate；tert-butyl N-[(2S,3R,5S)-5-amino-3-hydroxy-1,6-diphenylhexan-2-yl]carbamate
• CAS: 331767-03-4
• 化学式: C₂₃H₃₂N₂O₃
• 分子量: 384.519
• InChiKey: SDSHSQZUSKPIDM-PCCBWWKXSA-N

物化性质

• 熔点：
  130-132 °C
• 沸点：
  569.2±50.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  84.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (1S,2R,4S)-4-amino-1-benzyl-2-hydroxy-5-phenylpentylcarbamate 在 三氟乙酸 作用下， 以 水 为溶剂， 生成 (2S,3R,5S)-2,5-diamino-1,6-diphenyl-hexan-3-ol
  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：

  叔丁基(1S,2R,4S)-4-叠氮基-1-苄基-2-羟基-5-苯基戊基氨基甲酸酯 在 10percent Pd/C 氢气 作用下， 以 甲醇 为溶剂， 以100%的产率得到tert-butyl (1S,2R,4S)-4-amino-1-benzyl-2-hydroxy-5-phenylpentylcarbamate
  参考文献：
  名称：

  羟基乙烯二肽等排体的环氧醇途径：HIV蛋白酶抑制剂ABT-538（利托那韦）二氨基醇核心的新合成

  摘要：

  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。

  DOI：

  10.1039/b005804l

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。
• Asymmetric dihydroxylation route to a dipeptide isostere of a protease inhibitor: enantioselective synthesis of the core unit of ritonavir
  作者：Arun K. Ghosh、Dongwoo Shin、Packiarajan Mathivanan

  DOI：10.1039/a902518i

  日期：——

  An enantioselective synthesis of the dipeptide isostere of ritonavir has been accomplished utilizing Sharpless asymmetric hydroxylation as the key step.

  以 Sharpless 不对称羟基化为关键步骤，完成了利托那韦二肽电子等排体的对映选择性合成。
• Synthesis and Antimycobacterial Activity of Novel Amino Alcohols Containing Central Core of the Anti-HIV Drugs Lopinavir and Ritonavir
  作者：Claudia R. B. Gomes、Marcele Moreth、Danielle Cardinot、Valquiria Kopke、Wilson Cunico、Maria Cristina da Silva Lourenço、Marcus V. N. de Souza

  DOI：10.1111/j.1747-0285.2011.01244.x

  日期：2011.12

  Eleven new amino alcohol derivatives have been synthesized from reactions of lopinavir intermediate and heteroaromatic aldehyde in good yields. These compounds, the antiretrovirals (lopinavir and ritonavir) and lopinavir key intermediate were evaluated as antibacterial agents against Mycobacterium tuberculosis H37Rv using the Alamar Blue susceptibility test and their activity expressed as the minimum inhibitory concentration (MIC) in μm. Ten amino alcohols evaluated displayed significant activity (MIC between 6.15 and 108.4 μm) when compared to first‐line drug ethambutol (MIC = 15.9 μm). Three of them showed more activity than ethambutol (MIC = 6.15; 6.21 and 13.4 μm). The appreciable activity of these compounds can be considered an important finding for the rational design of new leads for anti‐TB compounds.
• 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.
• 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。