(S,E)-tert-butyl 3-oxo-1,6-diphenylhex-4-en-2-ylcarbamate | 198208-01-4

• 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: (S,E)-tert-butyl 3-oxo-1,6-diphenylhex-4-en-2-ylcarbamate
• 英文别名: tert-butyl (S,E)-3-oxo-1,6-diphenylhex-4-en-2-ylcarbamate；tert-butyl N-[(E,2S)-3-oxo-1,6-diphenylhex-4-en-2-yl]carbamate
• CAS: 198208-01-4
• 化学式: C₂₃H₂₇NO₃
• 分子量: 365.472
• InChiKey: SKKOTSANWYGBRM-QGRTWZNFSA-N

物化性质

• 沸点：
  530.765±50.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.091±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S,E)-tert-butyl 3-oxo-1,6-diphenylhex-4-en-2-ylcarbamate 在 palladium on activated charcoal sodium tetrahydroborate 、 sodium azide 、 18-冠醚-6 、 氢气 、 sodium hydride 、 caesium carbonate 、 甲基磺酰氯 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 红铝 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 1,2-二氯乙烷 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 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 0.42h， 生成 (S,E)-tert-butyl 3-oxo-1,6-diphenylhex-4-en-2-ylcarbamate
  参考文献：
  名称：

  Versatile and Stereoselective Synthesis of Diamino Diol Dipeptide Isosteres, Core Units of Pseudopeptide HIV Protease Inhibitors

  摘要：

  DOI：

  10.1021/jo971202p

文献信息

• Impact of Stereochemistry on Ligand Binding: X-ray Crystallographic Analysis of an Epoxide-Based HIV Protease Inhibitor
  作者：Fabio Benedetti、Federico Berti、Pietro Campaner、Lidia Fanfoni、Nicola Demitri、Folasade M. Olajuyigbe、Matteo De March、Silvano Geremia

  DOI：10.1021/ml500092e

  日期：2014.9.11

  A new pseudopeptide epoxide inhibitor, designed for irreversible binding to HIV protease (HIV-PR), has been synthesized and characterized in solution and in the solid state. However, the crystal structure of the complex obtained by inhibitor–enzyme cocrystallization revealed that a minor isomer, with inverted configuration of the epoxide carbons, has been selected by HIV-PR during crystallization.

  一种新的拟肽环氧化物抑制剂，设计用于与 HIV 蛋白酶 (HIV-PR) 的不可逆结合，已在溶液和固态中合成并表征。然而，通过抑制剂-酶共结晶获得的复合物的晶体结构表明，在结晶过程中，HIV-PR 选择了一种具有倒置环氧化物碳构型的次要异构体。有序假肽的结构表征，插入催化通道中，其环氧基团完整，提供了对抑制剂结合和 HIV-PR 立体选择性的更深入的了解，这有助于未来基于环氧化物的 HIV 抑制剂的开发。
• 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。
• A General and Highly Selective Chelate-Controlled Intermolecular Oxidative Heck Reaction
  作者：Jared H. Delcamp、Alexandria P. Brucks、M. Christina White

  DOI：10.1021/ja804120r

  日期：2008.8.27

  chelate-controlled intermolecular oxidative Heck reaction is reported that proceeds with a wide range of nonresonance stabilized alpha-olefin substrates and organoboron reagents to afford internal olefin products in good yields and outstanding regio- and E: Z stereoselectivities. Pd-H isomerization, common in many Heck reactions, is not observed under these mild, oxidative conditions. This is evidenced

  据报道，一种新型螯合物控制的分子间氧化 Heck 反应与各种非共振稳定的 α-烯烃底物和有机硼试剂一起进行，以良好的收率和出色的区域和 E:Z 立体选择性提供内烯烃产品。在许多 Heck 反应中常见的 Pd-H 异构化在这些温和的氧化条件下未观察到。这可以通过出色的 E:Z 选择性（在所有检查的情况下 >20:1）、近端立体中心的光学纯度没有侵蚀以及对未受保护的醇的耐受性来证明。值得注意的是，单一金属/配体组合，Pd/双-亚砜配合物 1，在广泛的偶联伙伴上催化该反应。鉴于高选择性和广泛的范围，
• Versatile and Stereoselective Synthesis of Diamino Diol Dipeptide Isosteres, Core Units of Pseudopeptide HIV Protease Inhibitors
  作者：Fabio Benedetti、Stanislav Miertus、Stefano Norbedo、Alessandro Tossi、Pavel Zlatoidzky

  DOI：10.1021/jo971202p

  日期：1997.12.1
• 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.