(4S)-1-benzyloxycarbonyl-4-(t-butyldimethylsilyloxy)-L-proline | 165177-74-2

• 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: (4S)-1-benzyloxycarbonyl-4-(t-butyldimethylsilyloxy)-L-proline
• 英文别名: N-Cbz-TBS-hydroxyproline；(2S,4S)-4-[tert-butyl(dimethyl)silyl]oxy-1-phenylmethoxycarbonylpyrrolidine-2-carboxylic acid
• CAS: 165177-74-2
• 化学式: C₁₉H₂₉NO₅Si
• 分子量: 379.528
• InChiKey: FGHHMWWDHGQPPT-HOTGVXAUSA-N

物化性质

• 沸点：
  472.4±45.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.87
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4S)-1-benzyloxycarbonyl-4-(t-butyldimethylsilyloxy)-L-proline 在 palladium on activated charcoal 盐酸 、 正丁基锂 、 氢气 、 N,N'-二环己基碳二亚胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙酸乙酯 为溶剂， 反应 9.0h， 生成
  参考文献：
  名称：

  Developing microcolin A analogs as biological probes

  摘要：

  Three microcolin A and B analogs have been synthesized. Their biological activity profiles were evaluated against several cell lines, revealing the existence of a structural determinant whose role in mediating the antiproliferative effect of the microcolins has heretofore gone unrecognized. While previously described as potent immunosuppressive natural products, we found that these microcolin analogs possessed no selective cytotoxicity when comparing immune cell versus nonimmune cell proliferation. In addition, the amino-terminus of microcolin A has been modified to incorporate a biotinylated polyethylene glycol linker. The biological activity of this biotinylated microcolin A analog was determined. This affinity reagent was shown to retain limited biological activity and thus can serve as a useful probe for elucidating the mechanism of action of microcolin A. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.020
• 作为产物：
  描述：

  (2S,4S)-1-benzyl 2-methyl 4-(tert-butyldimethylsilyloxy)pyrrolidine-1,2-dicarboxylate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 24.0h， 以83%的产率得到(4S)-1-benzyloxycarbonyl-4-(t-butyldimethylsilyloxy)-L-proline
  参考文献：
  名称：

  Synthesis of Microcolin B, a Potent New Immunosuppressant Using an Efficient Mixed Imide Formation Reaction

  摘要：

  Microcolin B, a potent new immunosuppressant isolated from blue-green alga Lyngbya majuscula off the Venezuelan coast, has been made using a methyl-directed asymmetric hydrogenation reaction with rhodium on alumina catalyst on lactone 4 for the synthesis of the key (R,R)-2,4-dimethyloctanoic acid fragment 1. A new, direct mixed imide formation reaction was also developed for the production of the unusual prolylpyrrolen-2-one 2 portion of microcolin. The pentafluorophenyl ester of CBZ-proline 5 was reacted with the lithium imidate of lactam 6, providing the mixed imide in 80% yield. Coupling of acid 1 with the N-terminus of the tripeptide, followed by coupling with pyrrolylproline 2, gave microcolin B. The new mixed-imide forming reaction was also applied to a formal total synthesis of microcolin A. The pentafluorophenyl ester of TBS-protected cis-hydroxyproline was coupled with lactam 6, and the resultant imide was converted to the key pyrrolylproline made previously far microcolin A.

  DOI：

  10.1021/jo970387x

文献信息

• Regioselective Synthesis of Nitrones by Decarboxylative Oxidation of<i>N</i>-Alkyl-<i>α</i>-amino Acids and Application to the Synthesis of 1-Azabicyclic Alkaloids
  作者：Hiroaki Ohtake、Yasushi Imada、Shun-Ichi Murahashi

  DOI：10.1246/bcsj.72.2737

  日期：1999.12

  were prepared by catalytic oxidation of the corresponding chiral pyrrolidines in a regioselective manner. These chiral cyclic nitrones, 17 and 45 are versatile intermediates for the synthesis of optically active nitrogen heterocycles, since stereoselective additions of carbon nucleophiles to these chiral nitrones can be readily performed. Typically, ZnI2-mediated addition of ketene t-butyldimethylsilyl

  在相转移条件下用 30% H2O2 溶液钨酸盐催化氧化 N-烷基-α-氨基酸，区域选择性地以良好的产率得到硝酮。使用该方法，实现了（R）-和（S）-4-（叔丁基二甲基甲硅烷氧基）-1-吡咯啉N-氧化物（（R）-17a和（S）-17a）的立体发散合成。此外，(R)-和(S)-3-(叔丁基二甲基甲硅烷氧基)-1-吡咯啉N-氧化物((R)-45和(S)-45)是通过相应手性吡咯烷的催化氧化制备的区域选择性方式。这些手性环状硝酮 17 和 45 是合成光学活性氮杂环的通用中间体，因为可以很容易地将碳亲核试剂立体选择性加成到这些手性硝酮上。通常，ZnI2 介导的乙烯酮叔丁基二甲基甲硅烷基甲基缩醛 (29a) 与 (R)-17a 的加成得到顺式加合物，(2R,4R)-[1,4-双(叔丁基二甲基甲硅烷氧基)吡咯烷-2-基]乙酸甲酯(cis-30)。相比之下，将乙炔锂 34 添加到硝酮 (R)-17a 中得到
• 具有抗肿瘤作用的化合物BA-X及其制备方法和应用
  申请人：雷鹏程

  公开号：CN108456239A

  公开（公告）日：2018-08-28

  本发明提供了一类具有结构通式1的化合物及其制备方法和在制备抗肿瘤药物中的应用。本发明化合物具有明显抑制肿瘤细胞系(HepG‑2、HT‑29、Hela、BGC‑823、A549)生长的活性，但对犬肾上皮细胞(MDCK)系毒性较小。其中，化合物BH‑26的对人结肠癌细胞系HT‑29、人宫颈癌细胞系Hela以及人胃癌细胞系BGC823抗增殖活性优于阳性药顺铂；但对犬正常肾上皮细胞MDCK的细胞毒性明显低于阳性药顺铂。
• Unified Approach to Deamination and Deoxygenation Through Isonitrile Hydrodecyanation: A Combined Experimental and Computational Investigation
  作者：Ziqi Jiao、Kyle T. Jaunich、Thomas Tao、Olivia Gottschall、Maxwell M. Hughes、Aneta Turlik、Alexander Schuppe

  DOI：10.1002/anie.202405779

  日期：——

  We report a general hydrodefunctionalization protocol using isonitrile intermediates. Employing photoredox catalysis, a nucleophilic boryl radical mediates the scission of a relatively inert C−NC bond, accomplishing deletion of the isonitrile group. This strategy applies to the hydrodefunctionalization of both amine and alcohol-containing compounds and extends to the reduction of carbonyls, olefins

  我们报告了使用异腈中间体的通用加氢脱官能化方案。利用光氧化还原催化作用，亲核硼基自由基介导相对惰性的 C−NC 键的断裂，从而实现异腈基团的删除。该策略适用于含胺和醇化合物的加氢脱官能化，并延伸至羰基、烯烃和烷基腈的还原。
• Synthesis of Microcolin B, a Potent New Immunosuppressant Using an Efficient Mixed Imide Formation Reaction
  作者：Merritt B. Andrus、Wenke Li、Robert F. Keyes

  DOI：10.1021/jo970387x

  日期：1997.8.1

  Microcolin B, a potent new immunosuppressant isolated from blue-green alga Lyngbya majuscula off the Venezuelan coast, has been made using a methyl-directed asymmetric hydrogenation reaction with rhodium on alumina catalyst on lactone 4 for the synthesis of the key (R,R)-2,4-dimethyloctanoic acid fragment 1. A new, direct mixed imide formation reaction was also developed for the production of the unusual prolylpyrrolen-2-one 2 portion of microcolin. The pentafluorophenyl ester of CBZ-proline 5 was reacted with the lithium imidate of lactam 6, providing the mixed imide in 80% yield. Coupling of acid 1 with the N-terminus of the tripeptide, followed by coupling with pyrrolylproline 2, gave microcolin B. The new mixed-imide forming reaction was also applied to a formal total synthesis of microcolin A. The pentafluorophenyl ester of TBS-protected cis-hydroxyproline was coupled with lactam 6, and the resultant imide was converted to the key pyrrolylproline made previously far microcolin A.
• Developing microcolin A analogs as biological probes
  作者：Amit K. Mandal、John Hines、Kouji Kuramochi、Craig M. Crews

  DOI：10.1016/j.bmcl.2005.06.020

  日期：2005.9

  Three microcolin A and B analogs have been synthesized. Their biological activity profiles were evaluated against several cell lines, revealing the existence of a structural determinant whose role in mediating the antiproliferative effect of the microcolins has heretofore gone unrecognized. While previously described as potent immunosuppressive natural products, we found that these microcolin analogs possessed no selective cytotoxicity when comparing immune cell versus nonimmune cell proliferation. In addition, the amino-terminus of microcolin A has been modified to incorporate a biotinylated polyethylene glycol linker. The biological activity of this biotinylated microcolin A analog was determined. This affinity reagent was shown to retain limited biological activity and thus can serve as a useful probe for elucidating the mechanism of action of microcolin A. (c) 2005 Elsevier Ltd. All rights reserved.