(S)-benzyl 2-((2S,3R)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-4-phenylbutanamido)-4-methylpentanoate | 246506-79-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (S)-benzyl 2-((2S,3R)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-4-phenylbutanamido)-4-methylpentanoate
• 英文别名: (S)-benzyl-2-((2S,3R)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-4-phenylbutanamido)-4-methylpentanoate；(S)-benzyl-2-((2S,3R)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-4-phenylbutyryl)-4-methylpentanoate；2-(3-tert-butoxycarbonylamino-2-hydroxy-4-phenylbutyrylamino)-4-methylpentanoic acid benzyl ester；Benzyl ((2S,3R)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-4-phenylbutanoyl)-L-leucinate；benzyl (2S)-2-[[(2S,3R)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-phenylbutanoyl]amino]-4-methylpentanoate
• CAS: 246506-79-6
• 化学式: C₂₈H₃₈N₂O₆
• 分子量: 498.62
• InChiKey: ARSSHOYLBQQZHJ-SGNDLWITSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  36
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-benzyl 2-((2S,3R)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-4-phenylbutanamido)-4-methylpentanoate 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 生成 乌苯美司
  参考文献：
  名称：

  由α-酮酰胺前体合成肽类α-羟基酰胺色淀素，探针素和Bestatin

  摘要：

  通过使用硼氢化锌立体定向还原α-酮基酰胺前体，可以制备氨基肽酶抑制剂，色氨酸，探针素和贝他汀。

  DOI：

  10.1016/s0040-4039(99)01143-0
• 作为产物：
  描述：

  methyl (2S,3R)-3-azido-2-hydroxy-4-phenylbutanoate 在 palladium on activated charcoal 氢气 、 sodium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 (S)-benzyl 2-((2S,3R)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-4-phenylbutanamido)-4-methylpentanoate
  参考文献：
  名称：

  New stereoselective synthesis of the peptidic aminopeptidase inhibitors bestatin, phebestin and probestin

  摘要：

  Peptidic aminopeptidase inhibitors, bestatin, phebestin and probestin have been prepared by stereo- and regiocontrolled reactions from a common alpha,beta-epoxy ester precursor. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(03)01799-4

文献信息

• Application of acyl cyanophosphorane methodology to the synthesis of protease inhibitors: poststatin, eurystatin, phebestin, probestin and bestatin
  作者：Harry H Wasserman、Anders K Petersen、Mingde Xia

  DOI：10.1016/s0040-4020(03)00860-3

  日期：2003.8

  Full details are given for the syntheses of the protease inhibitors, poststatin and eurystatin by the acyl cyanophosphorane coupling procedure used for the formation of α-keto amides. We have also extended this methodology to the syntheses of the related α-hydroxy amide natural products, phebestin, probestin and bestatin. The key step in the latter synthetic sequences involved diastereomeric selectivity

  通过用于形成α-酮酰胺的酰基氰基磷膦偶联方法，给出了蛋白酶抑制剂poststatin和eurystatin的合成的全部细节。我们还将这种方法扩展到了相关α-羟基酰胺天然产物phebestin，probestin和bestatin的合成中。后一合成顺序中的关键步骤涉及通过使用硼氢化锌将α-酮基前体还原为相应的α-羟基酰胺的非对映异构体选择性。
• 一种乌苯美司的合成方法
  申请人：山东益康药业股份有限公司

  公开号：CN104496843A

  公开（公告）日：2015-04-08

  本发明公开了一种乌苯美司的合成方法，以D-Boc-苯丙氨醛为原料，依次经过羟基腈的制备，腈基水解反应及氨基的保护，(2RS，3R)-3-叔丁氧酰胺基-2-羟基-4-苯基丁酸的手性拆分，(S)-苯基2-((2S,3R)-3-(叔丁氧酰胺基)-2-羟基-4-苯丁酰胺基)-4-甲基戊酸酯的合成，乌苯美司的合成。本发明合成方法解决了现有合成方法中所用到的拆分剂或者毒性太大(如马钱子碱)或者价格昂贵(α-苯乙胺)的缺点，并且合成方法步骤简单，成本低、避免了马钱子碱等试剂的使用；采用右旋氨基物作为手型拆分剂，价格低廉、操作简单，搅拌、重结晶时间缩短，大大提高了合成效率。
• MULTI-TARGETED UBENIMEX PRODRUG DERIVATIVE AND PREPARATION METHOD AND USE THEREOF
  申请人：Weifang Bochuang International Academy of Biotechnology and Medicine

  公开号：EP2947070B1

  公开（公告）日：2018-09-26
• Synthesis and biological characterization of ubenimex-fluorouracil conjugates for anti-cancer therapy
  作者：Yuqi Jiang、Xiaoyang Li、Jinning Hou、Yongxue Huang、Xuejian Wang、Yuping Jia、Qingwei Wang、Wenfang Xu、Jian Zhang、Yingjie Zhang

  DOI：10.1016/j.ejmech.2017.11.074

  日期：2018.1

  Previously a novel ubenimex-fluorouracil (5-FU) conjugate, BC-01 was identified and validated as a potent CD13 inhibitor with marked in vitro and in vivo antitumor potency. Herein, further structural modifications of the linker part of BC-01 was carried out to get more potent and stable ubenimex -fluorouracil conjugates. It was striking that most of these conjugates showed even more potent CD13 inhibitory activities than BC-01 and the approved CD13 inhibitor ubenimex. One representative compound 12a displayed significant in vitro anti-proliferation, pro-apoptosis, anti-metastasis, anti-angiogenesis and CD13(+) cell elimination effects. In vitro stability and in vivo pharmacokinetic study revealed that compound 12a could release ubenimex and 5-FU slowly, which could act as a mutual prodrug of ubenimex and 5-FU. Compared with 5-FU or 5-FU plus ubenimex, 12a exhibited superior in vivo antitumor growth efficiency, even in our mice model of 5-FU-resistant liver cancer. Moreover, 12a exhibited more potent in vivo anti-metastasis and lifespan extension effects compared to the approved 5-FU prodrug capecitabine. Collectively, these results suggest that further optimization and evaluation of 12a as a promising anticancer candidate are warranted to develop effective therapeutic agents for human liver cancer. (C) 2017 Elsevier Masson SAS. All rights reserved.
• Discovery of a novel chimeric ubenimex–gemcitabine with potent oral antitumor activity
  作者：Yuqi Jiang、Jinning Hou、Xiaoyang Li、Yongxue Huang、Xuejian Wang、Jingde Wu、Jian Zhang、Wenfang Xu、Yingjie Zhang

  DOI：10.1016/j.bmc.2016.09.033

  日期：2016.11

  Herein, a novel mutual prodrug BC-A1 was discovered by integrating ubenimex and gemcitabine into one molecule. Biological characterization revealed that compound BC-A1 could maintain both the anti-CD13 activity of ubenimex and the cytotoxic activity of gemcitabine in vitro. Further characterization also demonstrated that compound BC-A1 exhibited significant anti-invasion and anti-angiogenesis effects in vitro. The preliminary stability test of BC-A1 revealed that it could release gemcitabine in vitro. The in vivo anti-tumor results in liver cancer showed that at the same dosage, oral administration of BC-A1 was as potent as intraperitoneal administration of gemcitabine. This warranted the further research and development of the orally active prodrug BC-A1 because gemcitabine can not be orally administrated in clinic. (C) 2016 Elsevier Ltd. All rights reserved.