N^α-(9-Fluorenylmethyloxycarbonyl)-S-(2,4,6-trimethoxybenzyl)-L-cysteine | 140835-60-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N^α-(9-Fluorenylmethyloxycarbonyl)-S-(2,4,6-trimethoxybenzyl)-L-cysteine
• 英文别名: (2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[(2,4,6-trimethoxyphenyl)methylsulfanyl]propanoic acid
• CAS: 140835-60-5
• 化学式: C₂₈H₂₉NO₇S
• 分子量: 523.607
• InChiKey: RBRGDLFVCBTWNU-DEOSSOPVSA-N

物化性质

• 沸点：
  731.0±60.0 °C(Predicted)
• 密度：
  1.289±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  129
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N^α-(9-Fluorenylmethyloxycarbonyl)-S-(2,4,6-trimethoxybenzyl)-L-cysteine 在 碘 作用下， 以 氯仿 为溶剂， 生成 Bis(Fmoc)-cystine
  参考文献：
  名称：

  S-2,4,6-trimethoxybenzyl (Tmob): a novel cysteine protecting group for the N.alpha.-(9-fluorenylmethoxycarbonyl) (Fmoc) strategy of peptide synthesis

  摘要：

  The S-2,4,6-trimethoxybenzyl (Tmob) group can be introduced onto sulfhydryl functions from the corresponding alcohol, with acid catalysis, and is in turn removed rapidly by treatment with 30% trifluoroacetic acid-dichloromethane in the presence of phenol, thioanisole, and water (5% each) or 6% trifluoroacetic acid-dichloromethane in the presence of triethylsilane or triisopropylsilane (0.5%). The appropriate cysteine derivative was prepared and applied with other N(alpha)-Fmoc protected amino acids to the solid-phase syntheses of several model peptides. Acidolytic deblocking in the presence of cation scavengers and reducing agents gave the free thiol, whereas oxidative deblocking with iodine or thallium(III) trifluoroacetate provided an intramolecular disulfide. The chemistry of the S-Tmob group compares favorably to established chemistries with the acid-labile and oxidizable S-triphenylmethyl (trityl, Trt) group, as well as with the oxidizable S-acetamidomethyl (Acm) group.

  DOI：

  10.1021/jo00037a013
• 作为产物：
  描述：

  (9H-fluoren-9-yl)methyl azidoformate 、 S-(2,4,6-Trimethoxybenzyl)-L-cysteine 在 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 以76%的产率得到N^α-(9-Fluorenylmethyloxycarbonyl)-S-(2,4,6-trimethoxybenzyl)-L-cysteine
  参考文献：
  名称：

  S-2,4,6-trimethoxybenzyl (Tmob): a novel cysteine protecting group for the N.alpha.-(9-fluorenylmethoxycarbonyl) (Fmoc) strategy of peptide synthesis

  摘要：

  The S-2,4,6-trimethoxybenzyl (Tmob) group can be introduced onto sulfhydryl functions from the corresponding alcohol, with acid catalysis, and is in turn removed rapidly by treatment with 30% trifluoroacetic acid-dichloromethane in the presence of phenol, thioanisole, and water (5% each) or 6% trifluoroacetic acid-dichloromethane in the presence of triethylsilane or triisopropylsilane (0.5%). The appropriate cysteine derivative was prepared and applied with other N(alpha)-Fmoc protected amino acids to the solid-phase syntheses of several model peptides. Acidolytic deblocking in the presence of cation scavengers and reducing agents gave the free thiol, whereas oxidative deblocking with iodine or thallium(III) trifluoroacetate provided an intramolecular disulfide. The chemistry of the S-Tmob group compares favorably to established chemistries with the acid-labile and oxidizable S-triphenylmethyl (trityl, Trt) group, as well as with the oxidizable S-acetamidomethyl (Acm) group.

  DOI：

  10.1021/jo00037a013

文献信息

• Occurrence and Minimization of Cysteine Racemization during Stepwise Solid-Phase Peptide Synthesis¹^,²
  作者：Yongxin Han、Fernando Albericio、George Barany

  DOI：10.1021/jo9622744

  日期：1997.6.1

  suitable additives such as 1-hydroxybenzotriazole (HOBt) or 7-aza-1-hydroxybenzotriazole (HOAt) plus a tertiary amine base such as N,N-diisopropylethylamine (DIEA) or N-methylmorpholine (NMM). Under such conditions, the levels of racemization in the model peptide, expressed as the ratio of D:L peptide formed, were in the entirely unacceptable range of 5-33%. However, these levels were in general reduced

  与肽合成领域的常规智慧相反，N，S保护的半胱氨酸衍生物可以通过广泛使用的试剂和逐步掺入的方案进行大量消旋。已根据偶联条件和β-硫醇保护基（即S-乙酰氨基甲基（Acm），S-三苯甲基（三苯甲基或Trt），S-2,4,6-三甲氧基苄基）进行了系统研究。 （Tmob）和S-9H-黄嘌呤9-基（Xan），利用方便且定量的模型系统测定，包括从H-Gly HPLC分离H-Gly-L-Cys-Phe-NH（2） -D-Cys-Phe-NH（2）。例如，由，盐和铵盐，例如六氟磷酸（苯并三唑基氧基）三（二甲氨基）phosph（BOP）介导的偶联的标准方案，N-[（（1H-苯并三唑-1-基）（二甲基氨基）亚甲基] -N-甲基甲基六氟磷酸铵N-氧化物（HBTU），N-[[（（二甲基氨基）-1H-1,2,3-三唑[4,5] -b]吡啶基-1-基]亚甲基] -N-甲基甲基六氟磷酸铵N-氧化物（HATU）和（7-氮杂
• Evaluation of acid‐labile <scp> <i>S</i> </scp> ‐protecting groups to prevent Cys racemization in Fmoc solid‐phase peptide synthesis
  作者：Hajime Hibino、Yasuyoshi Miki、Yuji Nishiuchi

  DOI：10.1002/psc.2585

  日期：2014.1

  also the former method cannot reduce racemization of Cys(Trt) to an acceptable level (<1.0%) even when the preactivation procedure is omitted. Here, the 4,4′‐dimethoxydiphenylmethyl and 4‐methoxybenzyloxymethyl groups were demonstrated to be acid‐labile S‐protecting groups that can suppress racemization of Cys to an acceptable level (<1.0%) when the respective Fmoc derivatives are incorporated via the

  基于鏻和脲盐的试剂能够实现高效和有效的偶联反应，并且在肽化学中是必不可少的，尤其是在机器辅助 SPPS 中。然而，在叔胺存在下用这些试剂进行活化和偶联步骤后，已知 Cys 的 Fmoc 衍生物在其掺入过程中显着外消旋化。为了避免这种副反应，推荐使用一种由鏻/脲试剂与弱碱（如 2,4,6-三甲基吡啶）介导的偶联方法，该方法比通常使用的 DIEA 或碳二亚胺。然而，这些方法明显不如用于 SPPS 的标准方案，即在 DMF 中与鏻或脲试剂/DIEA 偶联的 1 分钟预活化程序，在偶联效率方面，即使省略了预活化程序，前一种方法也不能将 Cys(Trt) 的外消旋化降低到可接受的水平 (<1.0%)。在这里，4,4'-二甲氧基二苯基甲基和 4-甲氧基苄氧基甲基被证明是酸不稳定的当相应的 Fmoc 衍生物在 DMF 中的 DIEA 的帮助下通过鏻或脲试剂的标准 SPPS 方案加入时，S-保护基团可以将