6-methyl-5-[(tert-butyloxycarbonyl)amino]-4-oxo-2-isopropylheptanoic acid | 191930-96-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: 6-methyl-5-[(tert-butyloxycarbonyl)amino]-4-oxo-2-isopropylheptanoic acid
• 英文别名: (5S)-6-methyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxo-2-propan-2-ylheptanoic acid
• CAS: 191930-96-8
• 化学式: C₁₆H₂₉NO₅
• 分子量: 315.41
• InChiKey: XYSVPOWKBZCCBD-YUZLPWPTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  92.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-methyl-5-[(tert-butyloxycarbonyl)amino]-4-oxo-2-isopropylheptanoic acid 、 N^α,N^δ,N^ω-tris(benzyloxycarbonyl)-L-arginyl-N-methyl-L-norleucyl-L-aspartic acid β-cyclohexyl ester 生成 Arg-NMeNle-Asp-Val(k)Val
  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-[(tert-butyloxycarbonyl)amino]-3-isopropyl-1-octen-5-one 在 ruthenium(IV) oxide 、 sodium periodate 作用下， 以 水 、 丙酮 为溶剂， 以89%的产率得到6-methyl-5-[(tert-butyloxycarbonyl)amino]-4-oxo-2-isopropylheptanoic 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

文献信息

• PSEUDOPENTAPEPTIDES WITH IMMUNOMODULATING ACTIVITY
  申请人：Japan Tobacco Inc.

  公开号：EP0556405A1

  公开（公告）日：1993-08-25
• [EN] PSEUDOPENTAPEPTIDES WITH IMMUNOMODULATING ACTIVITY
  申请人：JAPAN TOBACCO INC.

  公开号：WO1993004080A1

  公开（公告）日：1993-03-04

  (EN) Pseudopeptides of formula ($g(a)) wherein AA1 is an arginyl residue; AA2 is a basic amino acid residue, a neutral/nonaromatic amino acid residue or proline residue or is an N-alkylated (1-6C) form thereof; AA3 is an aspartic acid or glutamic acid wherein the remaining carboxyl group may be esterified with alkyl (1-6C), or an alanine residue; AA4 is a neutral/nonaromatic amino acid residue; AA5 is a neutral/aromatic amino acid residue wherein one or more hydrogens of its aromatic portion can be substituted by NO2 or halogen, or is a neutral/nonpolar/large/nonaromatic amino acid residue or the N-alkylated (1-6C) form thereof; R is acyl (1-6C), arylsulfonyl, alkylsulfonyl, arylalkylsulfonyl or alkoxycarbonyl group; and R1 is -OH, -NR2R3 or -OR4 wherein each of R2 and R3 is hydrogen or an alkyl group (1-6C) and R4 is alkyl group (1-6C); and wherein at least one of the linkages I-IV is a modified peptide linkage -COCH2-, -CH(OH)CH2- or -CH2NH-, and the remaining linkages are -CONH- or -CON(CH3)-.(FR) Pseudopeptides répondant à la formule ($g(a)) dans laquelle AA1 représente un reste arginyle; AA2 représente un reste acide aminé fondamental, un reste acide aminé neutre/non aromatique ou un reste proline, ou bien représente une forme N-alkylée (1-6 C) d'un tel reste; AA3 représente un acide aspartique ou un acide glutamique dans lequel le groupe carboxyle restant peut être estérifié par alkyle (1-6 C), ou un reste alanine; AA4 représente un reste acide aminé neutre/non aromatique; AA5 représente un reste acide aminé neutre/aromatique dans lequel un ou plusieurs atomes d'hydrogène de sa partie aromatique peuvent être substitués par NO2 ou halogène, ou représente un reste acide aminé neutre/non polaire/grand/non aromatique, ou bien la forme N-alkylée (1-6 C) d'un tel reste; R représente un reste acyle (1-6 C), arylsulfonyle, alkylsulfonyle, arylalkylsulfonyle, ou alcoxycarbonyle; et R1 représente -OH, -NR2R3 ou -OR4, R2 et R3 représentant chacun un hydrogène ou un groupe alkyle (1-6 C), et R4 représentant un groupe alkyle (1-6 C). Dans ladite formule au moins une des liaisons I-IV est une liaison peptidique modifiée -COCH2-, -CH(OH)CH2- ou bien -CH2NH-, et les liaisons restantes sont -CONH- ou bien -CON(CH3)-.
• Stabilized Analogs of Thymopentin. 1. 4,5-Ketomethylene Pseudopeptides
  作者：Joseph I. DeGraw、Ronald G. Almquist、Charles K. Hiebert、William T. Colwell、Jac Crase、Takeshi Hayano、Amrit K. Judd、Linda Dousman、R. Lane Smith、William R. Waud、Itsuo Uchida

  DOI：10.1021/jm950803a

  日期：1997.7.1

  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.