(2'S,4'R)-methyl 1'-((S)-2-tert-butoxycarbonyl)amino-4-methylpentanoyl-4'-hydroxypyrrolidine-2'-carboxylate | 934552-55-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2'S,4'R)-methyl 1'-((S)-2-tert-butoxycarbonyl)amino-4-methylpentanoyl-4'-hydroxypyrrolidine-2'-carboxylate
• 英文别名: N-[N-(tert-butyloxycarbonyl)-L-leucyl]-4R-hydroxy-L-proline methyl ester；Boc-Leu-Hyp-OMe
• CAS: 934552-55-3
• 化学式: C₁₇H₃₀N₂O₆
• 分子量: 358.435
• InChiKey: BQXYJVLTJCFBLD-AGIUHOORSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.06
• 重原子数：
  25.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  105.17
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (2'S,4'R)-methyl 1'-((S)-2-tert-butoxycarbonyl)amino-4-methylpentanoyl-4'-hydroxypyrrolidine-2'-carboxylate 在 乙酰氯 、 三乙胺 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 18.0h， 以78%的产率得到3-异丁基-8-羟基六氢吡咯并[1,2-A]吡嗪-1,4-二酮
  参考文献：
  名称：

  通过定制化单元的选择性修饰合成具有定制N和α链的二酮哌嗪支架

  摘要：

  在DKP基板中对Hyp可定制单元的选择性操作允许生成具有四个空间定向的量身定制链的刚性支架。关键步骤是多米诺骨牌断裂-氧化过程，该过程允许生成N取代的DKP。本文描述了这种方法的通用性，其以高光学纯度生产用于材料和药物发现的支架。

  DOI：

  10.1002/adsc.202000470
• 作为产物：
  描述：

  L-羟基脯氨酸 在 氯化亚砜 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 28.0h， 生成 (2'S,4'R)-methyl 1'-((S)-2-tert-butoxycarbonyl)amino-4-methylpentanoyl-4'-hydroxypyrrolidine-2'-carboxylate
  参考文献：
  名称：

  Enantiomerically pure piperazines via NaBH4/I2 reduction of cyclic amides

  摘要：

  Enantiomerically pure (3S,7R,8aS)-3-phenyloctahydropyrrolo[1,2-a]pyrazine-7-ol, (3S,7R,8aS)-3-methyl octahydropyrrolo[1,2-a]pyrazine-7-ol, (3S,7R,8aS)-3-isopropyloctahydropyrrolo[1,2-a]pyrazine-7-ol and (35,7R,8aS)-3-isobutyloctahydropyrrolo[1,2-a]pyrazine-7-ol 16d were synthesized via preparation of the corresponding cyclic amides from enantiomerically pure L-proline and hydroxyproline derivatives followed by reduction using sodium borohydride-iodine. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2016.12.002

文献信息

• Conversion of “Customizable Units” into<i>N</i>-Alkyl Amino Acids and Generation of<i>N</i>-Alkyl Peptides
  作者：Carlos J. Saavedra、Carmen Carro、Dácil Hernández、Alicia Boto

  DOI：10.1021/acs.joc.9b00114

  日期：2019.7.5

  An efficient conversion of hydroxyproline “customizable” units into new amino acids with a variety of N-alkyl substituents is described. The process is versatile and can afford valuable N-methyl amino acids and N,O-acetals. In addition, it allows the introduction of N-homoallylic substituents and N-chains with terminal ester, ketone, or cyano groups. These chains could be used for peptide extension

  描述了羟脯氨酸“可定制”单元到具有各种N-烷基取代基的新氨基酸的有效转化。该方法是通用的，并且可以提供有价值的N-甲基氨基酸和N，O-乙缩醛。另外，它允许引入具有末端酯，酮或氰基的N-均烯丙基取代基和N-链。这些链可用于肽延伸或与其他分子的缀合（例如，通过烯烃复分解，肽连接等）。仅需两个步骤（对于R = CH 2 OAc）或三个步骤（裂解吡咯烷环，操纵α链和N-取代基）在无金属的温和条件下提供高光学纯度的产品。
• Structural Diversity using Hyp <i>“Customizable Units”</i> : <i>Proof‐of‐Concept</i> Synthesis of Sansalvamide‐Related Antitumoral Peptides
  作者：Fernando Cuevas、Carlos J. Saavedra、Ivan Romero‐Estudillo、Alicia Boto、Mario Ordóñez、Irene Vergara

  DOI：10.1002/ejoc.202001427

  日期：2021.2.12

  create structural diversity for biological screenings is highlighted in this proof‐of‐concept synthesis of new peptides related to the potent antitumoral Sansalvamide A. The selective modification of a parent peptide with a customizable Hyp unit rapidly afforded differently N1‐substituted linear and cyclic peptides. Hits with promising activity against MCF7 breast cancer line were detected therefrom.

  在概念验证中，与有效的抗肿瘤Sansalvamide A相关的新肽的合成突显了“可定制单位”为生物学筛选创造结构多样性的潜力。用可定制Hyp单位对母体肽进行的选择性修饰迅速提供了不同的结果N1取代的线性和环状肽。从中检测到对MCF7乳腺癌细胞具有有希望的活性的命中。
• Design, synthesis, inhibitory activity, and SAR studies of pyrrolidine derivatives as neuraminidase inhibitors
  作者：Jie Zhang、Qiang Wang、Hao Fang、Wenfang Xu、Ailin Liu、Guanhua Du

  DOI：10.1016/j.bmc.2007.01.020

  日期：2007.4

  A series of pyrrolidine derivatives were synthesized and evaluated for their ability to inhibit neuraminidase (NA) of influenza A virus (H3N2). All compounds were synthesized in good yields starting from commercially 4-hydroXy-L-proline using a suitable synthetic strategy. These compounds showed potent inhibitory activity against influenza A neuraminidase. Within this series, five compounds, 6e, 9c, 9e, 9f, and 10e, have good potency (IC50 = 1.56-2.71 mu M) which are compared to that the NA inhibitor Oseltarnivir (IC50 = 1.06 mu M), and could be used as lead compoundS in the future. (c) 2007 Elsevier Ltd. All rights reserved.
• Attenuation of TNF-α secretion by l-proline-based cyclic dipeptides produced by culture broth of Pseudomonas aeruginosa
  作者：Rukaiyya Khan、Ameer Basha、Ragavendra Goverdhanam、Poorna Chandra Rao、Yuhei Tanemura、Yoshinori Fujimoto、Ahil Sajeli Begum

  DOI：10.1016/j.bmcl.2015.10.075

  日期：2015.12

  To identify small molecule inhibitors of TNF-alpha, bioassay- and LC-MS-guided chemical investigation on EtOAc extract of Pseudomonas aeruginosa ABS-36 culture broth (EEPA) was performed, which yielded four proline-based cyclic dipeptides, cyclo(Gly-L-Pro) (1), cyclo(L-Pro-L-Phe) (2), cyclo(trans-4-hydroxy-L-Pro-L-Phe) (3) and cyclo(trans-4-hydroxy-L-Pro-L-Leu) (4). Compounds 1 and 3 exhibited potent inhibition of TNF-alpha release with IC50 values of 4.5 and 14.2 mu g/mL, respectively, while EEPA showed IC50 of 38.8 mu g/mL under lipopolysaccharide treated RAW 264.7 cell ELISA assay. Also, marked attenuation of mRNA-expression of TNF-alpha was shown by all compounds. In vivo testing in rats of EEPA and chemically synthesized 4 validated significant TNF-alpha reduction with 51% (500 mg/kg) and 79% (50 mg/kg), respectively. In addition, all compounds exhibited significant diminution of IL-1 beta and IL-6 mRNA-expression levels and NO production. All samples displayed only weak toxicity to lipopolysaccharide-induced RAW 264.7 cells. (C) 2015 Elsevier Ltd. All rights reserved.