6-methyl-5-[(tert-butyloxycarbonyl)amino]-4-oxo-2-benzylheptanoic acid | 191930-94-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 6-methyl-5-[(tert-butyloxycarbonyl)amino]-4-oxo-2-benzylheptanoic acid
• CAS: 191930-94-6
• 化学式: C₂₀H₂₉NO₅
• 分子量: 363.454
• InChiKey: ADDLFDVPJUIDSH-LWKPJOBUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.44
• 重原子数：
  26.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  92.7
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-叔丁氧羰基-N'-甲苯磺酰基-L-精氨酸 、 6-methyl-5-[(tert-butyloxycarbonyl)amino]-4-oxo-2-benzylheptanoic acid 、 N^α-[(butyloxycarbonyl)-N^ε-(2-chlorobenzyloxycarbonyl)-L-lysyl]-L-aspartic acid β-cyclohexyl ester 生成 Arg-Lys-Asp-Val(k)Phe
  参考文献：
  名称：

  Stabilized Analogs of Thymopentin. 1. 4,5-Ketomethylene Pseudopeptides

  摘要：

  The pentapeptide, thymopentin (Arg(1)-Lys(2)-Asp(3)-Val(4)-Tyr(5)) is known for its activity as an immunomodulating drug, but with limited half-life in plasma. In this first paper of a series of three studies, the synthesis of analogs stabilized at the peptide bond between the C-terminal amino acids via insertion of a ketomethylene moiety is described. N-Blocked pseudopeptides containing Val(k)Phe, Ala(k)Phe, and Val(k)Val units were prepared and attached to chloromethyl Merrifield resin via the carboxy terminal. Removal of the N-BOC group by trifluoroacetic acid was followed by sequential coupling with N-BOC dipeptides of aspartic acid to yield resin-bound N-BOC pseudotetrapeptides. Removal of N-BOC and coupling with N-BOC-r-N-tosylarginine followed by total cleavage of blocking groups and resin by HF afforded the target pseudopentapeptides. The analogs were found to compete favorably with thymopentin for binding to CEM cells, but binding was reduced by about 20-30% on average. All analogs showed significant enhancement of half-life versus thymopentin in mouse serum, but most showed only modest improvement in human serum. Insertion of proline or norleucine at position 2 in the chain caused a substantial increase in half-life (3-4-fold), while N-methylnorleucine conferred complete stability in the analogs.

  DOI：

  10.1021/jm950803a
• 作为产物：
  描述：

  7-methyl-6-[N-(tert-butyloxycarbonyl)amino]-3-benzyl-1-octen-5-one 在 ruthenium(IV) oxide 、 sodium periodate 作用下， 以 水 、 丙酮 为溶剂， 反应 1.0h， 以64%的产率得到6-methyl-5-[(tert-butyloxycarbonyl)amino]-4-oxo-2-benzylheptanoic acid
  参考文献：
  名称：

  Stabilized Analogs of Thymopentin. 1. 4,5-Ketomethylene Pseudopeptides

  摘要：

  The pentapeptide, thymopentin (Arg(1)-Lys(2)-Asp(3)-Val(4)-Tyr(5)) is known for its activity as an immunomodulating drug, but with limited half-life in plasma. In this first paper of a series of three studies, the synthesis of analogs stabilized at the peptide bond between the C-terminal amino acids via insertion of a ketomethylene moiety is described. N-Blocked pseudopeptides containing Val(k)Phe, Ala(k)Phe, and Val(k)Val units were prepared and attached to chloromethyl Merrifield resin via the carboxy terminal. Removal of the N-BOC group by trifluoroacetic acid was followed by sequential coupling with N-BOC dipeptides of aspartic acid to yield resin-bound N-BOC pseudotetrapeptides. Removal of N-BOC and coupling with N-BOC-r-N-tosylarginine followed by total cleavage of blocking groups and resin by HF afforded the target pseudopentapeptides. The analogs were found to compete favorably with thymopentin for binding to CEM cells, but binding was reduced by about 20-30% on average. All analogs showed significant enhancement of half-life versus thymopentin in mouse serum, but most showed only modest improvement in human serum. Insertion of proline or norleucine at position 2 in the chain caused a substantial increase in half-life (3-4-fold), while N-methylnorleucine conferred complete stability in the analogs.

  DOI：

  10.1021/jm950803a