(S)-2-{[(1S,2R,3S,4R)-3-((S)-1-Carboxy-3-methyl-butylcarbamoyl)-bicyclo[2.2.1]hept-5-ene-2-carbonyl]-amino}-4-methyl-pentanoic acid | 261360-99-0

• 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: (S)-2-{[(1S,2R,3S,4R)-3-((S)-1-Carboxy-3-methyl-butylcarbamoyl)-bicyclo[2.2.1]hept-5-ene-2-carbonyl]-amino}-4-methyl-pentanoic acid
• CAS: 261360-99-0
• 化学式: C₂₁H₃₂N₂O₆
• 分子量: 408.495
• InChiKey: VZHULVWUAVLMPF-FHULIHMCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.66
• 重原子数：
  29.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  132.8
• 氢给体数：
  4.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (S)-2-{[(1S,2R,3S,4R)-3-((S)-1-Carboxy-3-methyl-butylcarbamoyl)-bicyclo[2.2.1]hept-5-ene-2-carbonyl]-amino}-4-methyl-pentanoic acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 36.25h， 生成 methyl (2S)-2-[[(2S)-2-[[(5S,8S,11S,12R,15S,16R,19S,22S)-22-[[(2S)-1-[[(2S)-1-methoxy-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]-8,19-bis(2-methylpropyl)-2,7,10,17,20,25-hexaoxo-3,24-dioxa-6,9,18,21-tetrazahexacyclo[24.5.1.11,28.112,15.126,30.011,16]pentatriacont-13-ene-5-carbonyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoate
  参考文献：
  名称：

  具有发夹结构的降冰片烯约束环肽：设计，合成，构象和膜离子转运。

  摘要：

  在使用降冰片烯单元作为桥连配体的基础上，已经设计了新的发夹环肽家族。如此处所示，在氨基酸选择，环大小和第二个桥连配体的性质方面，设计很灵活，其中制备了大量的降冰片烯环肽，这些环肽含有各种氨基酸，环大小各不相同从12到29元，第二个桥连配体的选择是刚性降冰片烯（11、13a，b），金刚烷单元（7a，b和8）或柔性胱氨酸残基（4a，b和10） ）。内置手柄（作为受保护的COOH基团）的存在允许连接此处所示的Leu-Leu，Val-Val或Aib-Aib侧基分别连接在4b，7b和13b中的各种亚基。如（1）1 H NMR和CD光谱所示，这类新型的受限环肽被证明采用β-折叠或发夹状构象。膜离子迁移研究表明，对称放置在环外部的含有Leu-Leu或Val-Val侧基的降冰片烯环肽4b和7b在运输特定单价阳离子方面显示出高效率和选择性。该性质可归因于降冰片烯单元诱导的发夹状结构，因为在外部包含两对Leu

  DOI：

  10.1021/jo9912045
• 作为产物：
  描述：

  3,6-endomethylene-1,2,3,6-tetrahydrophthalic anhydride 在 sodium hydroxide 、 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 16.25h， 生成 (S)-2-{[(1S,2R,3S,4R)-3-((S)-1-Carboxy-3-methyl-butylcarbamoyl)-bicyclo[2.2.1]hept-5-ene-2-carbonyl]-amino}-4-methyl-pentanoic acid
  参考文献：
  名称：

  Demonstration of endo-cis-(2S,3R)-Bicyclo[2.2.1]hept-5-en-2,3- dicarbonyl Unit as a Reverse-Turn Scaffold and Nucleator of Two-Stranded Parallel β-Sheets:  Design, Synthesis, Crystal Structure, and Self-Assembling Properties of Norborneno Peptide Analogues

  摘要：

  endo-cis-(2S,3R)-Bicyclo[2.2.1]hept-5-en (norbornene) dicarbonyl unit with a built-in U-architecture has been demonstrated to be an excellent reverse-turn molecular scaffold. A large variety of endo-cis-(2S,3R)-norborneno bispeptides containing almost all of the coded amino acids were synthesized and examined for conformational preferences by H-1 NMR, FT-IR, CD, and X-ray crystallographic studies. While FT-IR and H-1 NMR variable-temperature studies ruled out the presence of any significant amount of intramolecular hydrogen bonding in simple bispeptides (3a-h) (except in Aib bispeptide), the CD studies were clearly in favor of a beta-turn type structure. Single-crystal X-ray studies on Aib, Val and Leu containing norborneno bispeptides (3b-d) provided convincing proof for the presence of reverse-turn conformation. While the interstrand C-alpha-C-alpha' distances (5.2-5.7 Angstrom) were well within the range of those for beta-turn structures, no interstrand intramolecular hydrogen bonding was seen in Val and Leu bispeptides; the Aib bispeptide forms a seven-membered hydrogen-bonded ring, thus, showing that the norbornene (2S,3R)-dicarbonyl template assembles peptide chains in reverse-turn conformation by virtue of its built-in U-shaped architecture at these positions, and hydrogen bonding may not be necessary to stabilize the turn structure. The endo-cis-(2S,3R) orientation of bispeptide chains is essential for turn structure as shown by the crystal structure of trans-(2R, 3R) and trans-(2S,3S) derivative of Val bispeptide wherein the two peptide chains move away from each other with the C-alpha-C-alpha' distance increasing to 7.1-8.2 Angstrom. The norbornene 5,6-double bond was hydrogenated to 5,6-dihydro derivative which showed almost the same CD spectrum as its olefinic analogue. Oxidative cleavage [Ru (VIII)] of the 5,6-double bond in norborneno bispeptides, as demonstrated with Leu bispeptide, afforded novel cyclopentanoid peptide analogues. The promise of norbornene unit as a template for nucleating the formation of two-stranded parallel beta-sheets with minimum structural complexity is shown by the preparation of higher members of norborneno bispeptides with the general structure NBE(Pep)(2) [NBE = endo-cis-(2S,3R)-bicyclo[2.2.1]hept-5-en (norbornene) dicarbonyl unit; Pep = peptide strand with two, three, or four (same or different) amino acid residues]. In H-1 NMR, the high (3)J(HN alpha) values (7.0-9.3 Hz) observed for the amide protons (Table 5) coupled with the presence of medium to strong intrastrand sequential ROE connectivities d(alpha N(i,i+1)) spanning the entire three- or four-residue sequence in the peptide strands of 9a-e and 10 and the exhibition of relatively low-temperature coefficients (d delta/dT = -0.2 to -3.4 ppb/K) for amide protons in DMSO-d(6) solvent (Table 4) clearly suggested that hydrogen-bonded beta-sheet conformers dominate the population. FT-IR and CD studies provided further support for parallel beta-sheet structures. A particularly unique feature of the norborneno bispeptides is their strong tendency to self-assemble in the solid state.Thus, while endo-cis-(2S,3R)-Aib bispeptide (3b) forms 16-membered hydrogen bonded centrosymmetric dimers, the half-ester half-acid and the dicarboxylic acid derivatives of 3b self-assemble to form highly ordered hydrogen-bonded molecular ribbons. The Val and Leu cis-(2S, 3R)-bispeptides organize into hydrogen-bonded chains and the trans isomer of Val bispeptide self-assembles into hydrogen-bonded beta-sheet ribbon.

  DOI：

  10.1021/ja980143+