Cbz-phenylalanine 4-pyridylthioester | 521305-70-4

• 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: Cbz-phenylalanine 4-pyridylthioester
• 英文别名: S-pyridin-4-yl (2S)-3-phenyl-2-(phenylmethoxycarbonylamino)propanethioate
• CAS: 521305-70-4
• 化学式: C₂₂H₂₀N₂O₃S
• 分子量: 392.478
• InChiKey: KAEMRKAKFDATTH-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  93.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Cbz-phenylalanine 4-pyridylthioester 在 samarium diiodide 、 水 、 三甲基铝 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 72.0h， 生成 benzyl 2-(2-benzyl-5-(benzyloxycarbonylamino)-4-oxo-6-phenylhexanoylamino)-4-methylpentanoate
  参考文献：
  名称：

  扩大SmI 2促进的酰基型自由基加成反应的范围

  摘要：

  观察到简单羧酸和氨基酸的N-酰基恶唑烷酮与取代的丙烯酰胺和丙烯酸酯成功进行了SmI 2促进的偶联，提供了多种官能化的γ-酮酰胺和酯，收率达到85％。由于先前发现许多这些还原偶联在使用相应的4-吡啶基硫代酯方面是无效的，因此该方法的适用性已得到显着改善。该方法适用于制备与两种有效的天冬氨酸蛋白酶抑制剂，肾素抑制剂阿利吉仑和γ-分泌酶抑制剂L-685,458有关的结构。最后，用于制备一个方便的两步程序Ñ的酰基恶唑烷酮Ñ已经设计了-保护的氨基酸，其提供了始终良好的相应酰亚胺的产率。

  DOI：

  10.1021/jo061299s
• 作为产物：
  描述：

  吡啶-4(1H)-硫酮 、 N-苄氧羰基-L-苯丙氨酸 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以81%的产率得到Cbz-phenylalanine 4-pyridylthioester
  参考文献：
  名称：

  通过收敛的酰基样自由基加成策略合成三肽Arg-Gly-Leu的羟乙烯等排体

  摘要：

  几步合成了三肽Arg-Gly-Leu的羟基乙烯等排体，它是新型基于环肽的uPA抑制剂的重要片段，采用二碘化sa促进偶合的4-硫代吡啶酯的偶联为关键步骤。ñ α -Fmoc-或ñ α -CBZ-保护的升与鸟氨酸的ñ -丙烯酰基衍生物的升-亮氨酸甲酯。在手性中心在α-位与酮的偶合条件下，未发生差向异构化。在甲醇的存在下，通过相同的单电子还原剂促进了由该自由基反应获得的Cbz保护的氨基酮的立体选择性还原，从而提供了非对映选择性为85:15的顺氨基醇。在甲醇中使用三叔丁氧基氢化铝锂，几乎只能获得相应的反异构体。随后通过引入胍基来精制反异构体中的鸟氨酸部分，然后水解C末端酯键并保护醇作为其叔醇丁基二甲基甲硅烷基醚提供了所需的三肽模拟物。用于与自由基加成反应所需的长的反应时间Ñ δ -Boc-升鸟氨酸（最多5天）导致了短研究，其中一系列Cbz-保护的氨基酸的4-硫代吡啶酯用两种丙烯酸酯反应。而Ñ δ

  DOI：

  10.1021/jo0505775

文献信息

• Formal Total Synthesis of the Potent Renin Inhibitor Aliskiren:  Application of a SmI₂-Promoted Acyl-like Radical Coupling
  作者：Karl B. Lindsay、Troels Skrydstrup

  DOI：10.1021/jo060296c

  日期：2006.6.1

  A formal total synthesis of the potent renin inhibitor aliskiren is disclosed exploiting an alternative coupling strategy recently developed by this laboratory for the preparation of the hydroxyethylene isostere-based class of protease inhibitors. The thioester derivative of the amino acid representing the C5−C9 fragment of the aliskiren carbon skeleton underwent a carbon chain extension via a SmI2-promoted

  公开了有效的肾素抑制剂阿利吉仑的正式全合成，其利用了由该实验室最近开发的用于制备基于羟乙烯等排酯的一类蛋白酶抑制剂的替代偶联策略。通过SMI硫酯衍生物表示阿利吉仑碳骨架的C5-C9片段的氨基酸的进行了碳链延长2促进的自由基加成到Ñ丙烯酸丁酯。具有正确的相对构型的C 3-异丙基的引入是通过伴随内酯化的立体选择性还原获得的酮，然后与丙酮进行醛醇缩合反应而完成的。进一步的官能团和保护基团的操作最终使阿利吉仑从相应的受完全保护的非天然氨基酸开始进行正式的全合成，最终完成了10个步骤。
• Further studies in the acyl-type radical additions promoted by SmI 2 : mechanistic implications and stereoselective reduction of the keto-functionality
  作者：Lise M Mikkelsen、Christina M Jensen、Bettina Høj、Peter Blakskjær、Troels Skrydstrup

  DOI：10.1016/j.tet.2003.07.016

  日期：2003.12

  Attempts were made to promote the carbonyl coupling of cyclohexanone to 4-pyridylthioesters of N-carbamate-protected amino acids with the one electron reducing agent, samarium diiodide. Such reactions proved unsuccessful due to the inability of the ketyl-type radical anion intermediate to be reduced to the corresponding dianion at -78degreesC. Nevertheless, these results explain our recently published work on the high efficiency of the SmI2-mediated acyl-type radical additions of the same thioesters with electron deficient alkenes [J. Am. Chem. Soc. 2003, 125, 4030]. A study was also undertaken to examine methods for the stereoselective reduction of N-carbamate-protected amino ketones to either the syn- or anti-vicinal amino alcohols. In most cases, LiAl(0-t-Bu)(3)H and (S)-Alpine-Hydride were found to effectively provide the anti- and syn-amino alcohols, respectively. The SmI2-promoted reduction of the same ketones afforded a majority of the syn-isomer with selectivities of approximately 5:1. However, in one case, the SmI2-promoted reduction was found to be more effective than that of (S)-Alpine-Hydride. (C) 2003 Elsevier Ltd. All rights reserved.
• SmI₂ Reduced Thioesters as Synthons of Unstable Acyl Radicals:  Direct Synthesis of Potential Protease Inhibitors via Intermolecular Radical Addition
  作者：Peter Blakskjær、Bettina Høj、Ditte Riber、Troels Skrydstrup

  DOI：10.1021/ja029662+

  日期：2003.4.1

  Aromatic alpha-heterosubstituted thioesters were found to undergo radical 1,4-addition reactions to a series of alpha,beta-unsaturated amides and one ester when subjected to the single electron reducing agent, samarium diiodide, at -78 degrees C. These thioesters derived from alpha-amino acids represent a synthetically useful synthon of unstable acyl radicals. This reaction conveniently provides access to gamma-ketoamides and esters in yields up to 90%, structures that are common in various protease inhibitors derived from peptides. Examples with acryloyl and methacryloyl derivatives of alpha-amino acids and dipeptides lead directly to tri- and tetrapeptide mimetics possessing the gamma-ketoamide functionality. No epimerization was observed with the mild conditions used for these reactions.
• Synthesis of a Hydroxyethylene Isostere of the Tripeptide Arg-Gly-Leu via a Convergent Acyl-like Radical Addition Strategy
  作者：Christina M. Jensen、Karl B. Lindsay、Peter Andreasen、Troels Skrydstrup

  DOI：10.1021/jo0505775

  日期：2005.9.1

  important fragment of a novel cyclic-peptide-based uPA inhibitor, was synthesized in few steps employing as the key step a samarium diiodide promoted coupling of either the 4-thiopyridyl ester of Nα-Fmoc- or Nα-Cbz-protected l-ornithine with the N-acryloyl derivative of l-leucine methyl ester. Epimerization under the coupling conditions at the chiral center in the α-position to the ketone was demonstrated

  几步合成了三肽Arg-Gly-Leu的羟基乙烯等排体，它是新型基于环肽的uPA抑制剂的重要片段，采用二碘化sa促进偶合的4-硫代吡啶酯的偶联为关键步骤。ñ α -Fmoc-或ñ α -CBZ-保护的升与鸟氨酸的ñ -丙烯酰基衍生物的升-亮氨酸甲酯。在手性中心在α-位与酮的偶合条件下，未发生差向异构化。在甲醇的存在下，通过相同的单电子还原剂促进了由该自由基反应获得的Cbz保护的氨基酮的立体选择性还原，从而提供了非对映选择性为85:15的顺氨基醇。在甲醇中使用三叔丁氧基氢化铝锂，几乎只能获得相应的反异构体。随后通过引入胍基来精制反异构体中的鸟氨酸部分，然后水解C末端酯键并保护醇作为其叔醇丁基二甲基甲硅烷基醚提供了所需的三肽模拟物。用于与自由基加成反应所需的长的反应时间Ñ δ -Boc-升鸟氨酸（最多5天）导致了短研究，其中一系列Cbz-保护的氨基酸的4-硫代吡啶酯用两种丙烯酸酯反应。而Ñ δ
• Expanding the Scope of the Acyl-Type Radical Addition Reactions Promoted by SmI₂
  作者：Jakob Karaffa、Karl B. Lindsay、Troels Skrydstrup

  DOI：10.1021/jo061299s

  日期：2006.10.1

  N-Acyl oxazolidinones of simple carboxylic acids and amino acids were observed to undergo successful SmI2-promoted couplings with substituted acrylamides and acrylates, affording a variety of functionalized γ-ketoamides and -esters with yields attaining 85%. As many of these reductive couplings were previously found to be ineffective employing the corresponding 4-pyridylthio esters, the applicability

  观察到简单羧酸和氨基酸的N-酰基恶唑烷酮与取代的丙烯酰胺和丙烯酸酯成功进行了SmI 2促进的偶联，提供了多种官能化的γ-酮酰胺和酯，收率达到85％。由于先前发现许多这些还原偶联在使用相应的4-吡啶基硫代酯方面是无效的，因此该方法的适用性已得到显着改善。该方法适用于制备与两种有效的天冬氨酸蛋白酶抑制剂，肾素抑制剂阿利吉仑和γ-分泌酶抑制剂L-685,458有关的结构。最后，用于制备一个方便的两步程序Ñ的酰基恶唑烷酮Ñ已经设计了-保护的氨基酸，其提供了始终良好的相应酰亚胺的产率。