(2S,3R,4S,6E)-3-羟基-4-甲基-2-(甲氨基)-6-辛烯酸 | 104372-53-4

• 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
• 中文名称: (2S,3R,4S,6E)-3-羟基-4-甲基-2-(甲氨基)-6-辛烯酸
• 英文名称: (2S,3R,4S,6E)-3-hydroxy-4-methyl-2-(methylamino)-6-octenoic acid
• 英文别名: (E,2S,3R,4S)-3-hydroxy-4-methyl-2-(methylamino)oct-6-enoic acid
• CAS: 104372-53-4
• 化学式: C₁₀H₁₉NO₃
• 分子量: 201.266
• InChiKey: AHQFCPOIMVMDEZ-VSXNJVAHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,3R,4S,6E)-3-羟基-4-甲基-2-(甲氨基)-6-辛烯酸 在 N-甲基吗啉 、 盐酸 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 为溶剂， 反应 56.0h， 生成 ((2S,3R,4S,6E)-3-hydroxy-4-methyl-2-(methylamino)-6-octenoyl)-L-2-aminobutyryl-sarcosyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl-L-alanine benzyl ester
  参考文献：
  名称：

  Synthesis, biological activity, and conformational analysis of (2S,3R,4S)-MeBmt-cyclosporin, a novel 1-position epimer of cyclosporin A

  摘要：

  Cyclosporin A (CsA, 1), an immunosuppressive cyclic undecapeptide, contains a unique amino acid, (4R)-4-[(E)-butenyl]-4,N-dimethyl-L-threonine (MeBmt), that appears to be critically involved in the biological activity of CsA. In order to further explore the effect that structural elements in MeBmt have on the conformation and biological activity of CsA, the 4-epimer of MeBmt [(4S)-MeBmt, 2] and the corresponding CsA analogue [(4S)-MeBmt1-CsA, 3] have been synthesized. Biological assay using concanavalin A stimulated thymocytes indicated that (4S)-MeBmt1-CsA (3) has only 2-4% immunosuppressive activity relative to CsA. The NMR analysis by 1D and 2D NMR methods establishes the conformation of 3, of which the 33-membered cyclic peptide ring system in chloroform is very similar to that of CsA. However, the NMR analysis also reveals that the 1-position side chain orientation in (4S)-MeBmt1-CsA (3) is very different from that of CsA. Specifically, the (4S)-MeBmt alpha,beta-torsion angle (chi 1) has been rotated approximately 120 degrees relative to that of CsA, and the orientation of the butenyl side chain relative to the 33-membered peptide backbond is different. The orientation of the (4S)-MeBmt side chain is consistent with the possible conformations calculated for (4S)-MeBmt1-CsA (3) by using molecular mechanics (in vacuo) calculations. The conformational analysis suggests that the loss of biological activity for 3 results from an altered conformation of the 1-position side chain relative to the peptide backbond due to the changed chirality at C4 of MeBmt.

  DOI：

  10.1021/jm00128a048
• 作为产物：
  描述：

  methyl (4S,5R)-3-methyl-5-<(1'S,3'E)-1'-methyl-3'-pentenyl>-2-oxazolidinone-4-carboxylate 在 氢氧化钾 作用下， 以 水 为溶剂， 生成 (2S,3R,4S,6E)-3-羟基-4-甲基-2-(甲氨基)-6-辛烯酸
  参考文献：
  名称：

  不对称甘氨酸烯醇醛醇反应：环孢菌素不寻常氨基酸 MeBmt 的合成

  摘要：

  合成 de l'acide (hydroxy-3methyl-4methylamino-2) octene-6oique apr aldolisation entre l'enolate de la (benzyl-4 isothiocyanatoacetyl-3) oxazolidone-2 et des alcenals

  DOI：

  10.1021/ja00281a049

文献信息

• Asymmetric glycine enolate aldol reactions: synthesis of cyclosporin's unusual amino acid, MeBmt
  作者：David A. Evans、Ann E. Weber

  DOI：10.1021/ja00281a049

  日期：1986.10

  Synthese de l'acide (hydroxy-3 methyl-4 methylamino-2) octene-6oique apr aldolisation entre l'enolate de la (benzyl-4 isothiocyanatoacetyl-3) oxazolidone-2 et des alcenals

  合成 de l'acide (hydroxy-3methyl-4methylamino-2) octene-6oique apr aldolisation entre l'enolate de la (benzyl-4 isothiocyanatoacetyl-3) oxazolidone-2 et des alcenals
• RICH, DANIEL H.;SUN, CHONG-QING;GUILLAUME, DOMINIQUE;DUNLAP, BRIAN;EVANS,+, J. MED. CHEM., 32,(1989) N, C. 1982-1987
  作者：RICH, DANIEL H.、SUN, CHONG-QING、GUILLAUME, DOMINIQUE、DUNLAP, BRIAN、EVANS,+

  DOI：——

  日期：——
• Synthesis, biological activity, and conformational analysis of (2S,3R,4S)-MeBmt-cyclosporin, a novel 1-position epimer of cyclosporin A
  作者：Daniel H. Rich、Chong Qing Sun、Dominique Guillaume、Brian Dunlap、David A. Evans、Ann E. Weber

  DOI：10.1021/jm00128a048

  日期：1989.8

  Cyclosporin A (CsA, 1), an immunosuppressive cyclic undecapeptide, contains a unique amino acid, (4R)-4-[(E)-butenyl]-4,N-dimethyl-L-threonine (MeBmt), that appears to be critically involved in the biological activity of CsA. In order to further explore the effect that structural elements in MeBmt have on the conformation and biological activity of CsA, the 4-epimer of MeBmt [(4S)-MeBmt, 2] and the corresponding CsA analogue [(4S)-MeBmt1-CsA, 3] have been synthesized. Biological assay using concanavalin A stimulated thymocytes indicated that (4S)-MeBmt1-CsA (3) has only 2-4% immunosuppressive activity relative to CsA. The NMR analysis by 1D and 2D NMR methods establishes the conformation of 3, of which the 33-membered cyclic peptide ring system in chloroform is very similar to that of CsA. However, the NMR analysis also reveals that the 1-position side chain orientation in (4S)-MeBmt1-CsA (3) is very different from that of CsA. Specifically, the (4S)-MeBmt alpha,beta-torsion angle (chi 1) has been rotated approximately 120 degrees relative to that of CsA, and the orientation of the butenyl side chain relative to the 33-membered peptide backbond is different. The orientation of the (4S)-MeBmt side chain is consistent with the possible conformations calculated for (4S)-MeBmt1-CsA (3) by using molecular mechanics (in vacuo) calculations. The conformational analysis suggests that the loss of biological activity for 3 results from an altered conformation of the 1-position side chain relative to the peptide backbond due to the changed chirality at C4 of MeBmt.