(2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6-octenoyl-L-2-aminobutyrylsarcosyl-N-methylleucylvalyl-N-methylleucylalanine benzyl ester | 81135-33-3

• 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: (2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6-octenoyl-L-2-aminobutyrylsarcosyl-N-methylleucylvalyl-N-methylleucylalanine benzyl ester
• 英文别名: MeBmt-Abu-Sar-MeLeu-Val-MeLeu-Ala-Bzl；HMeBmt-Abu-Sar-MeLeu-Val-MeLeu-Ala-OBn；Me-Bmt(E)-Abu-Sar-N(Me)Leu-Val-N(Me)Leu-Ala-OBn；benzyl (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(E,2S,3R,4R)-3-hydroxy-4-methyl-2-(methylamino)oct-6-enoyl]amino]butanoyl]-methylamino]acetyl]-methylamino]-4-methylpentanoyl]amino]-3-methylbutanoyl]-methylamino]-4-methylpentanoyl]amino]propanoate
• CAS: 81135-33-3
• 化学式: C₄₆H₇₇N₇O₉
• 分子量: 872.159
• InChiKey: UHTMSMVBUZZIMF-MKWNDYNSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  62
• 可旋转键数：
  27
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  207
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6-octenoyl-L-2-aminobutyrylsarcosyl-N-methylleucylvalyl-N-methylleucylalanine benzyl ester 、 Boc-D-Ala-MeLeu-MeLeu-MeVal-OH 在 N-甲基吗啉 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以52%的产率得到Boc-D-Ala-MeLeu-MeLeu-MeVal-MeBmt-Abu-Sar-MeLeu-Val-MeLeu-Ala-OBn
  参考文献：
  名称：

  Expanding the Limits of Isonitrile-Mediated Amidations: On the Remarkable Stereosubtleties of Macrolactam Formation from Synthetic Seco-Cyclosporins

  摘要：

  The scope of isonitrile-mediated amide bond-forming reactions is further explored in this second-generation synthetic approach to cyclosporine (cyclosporin A). Both type I and type II amidations are utilized in this effort, allowing access to epimeric cyclosporins A and H from a single precursor by variation of the coupling reagents. This work lends deeper insight into the relative acylating ability of the formimidate carboxylate mixed anhydride (FCMA) intermediate, while shedding light on the far-reaching impact of remote stereochemical changes on the effective preorganization of seco-cyclosporins.

  DOI：

  10.1021/ja2103372
• 作为产物：
  描述：

  (2S,3R,4R,6E)-3-羟基-4-甲基-2-(甲基氨基)-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 32.0h， 生成 (2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6-octenoyl-L-2-aminobutyrylsarcosyl-N-methylleucylvalyl-N-methylleucylalanine benzyl ester
  参考文献：
  名称：

  Synthesis of D-lysine8-cyclosporine A. Further characterization of BOP-Cl in the 2-7 hexapeptide fragment synthesis

  摘要：

  DOI：

  10.1021/jo00296a061

文献信息

• Synthesis and neurotrophic activity of nonimmunosuppressant cyclosporin A derivatives
  作者：Ling Wei、Joseph P Steiner、Gregory S Hamilton、Yong-Qian Wu

  DOI：10.1016/j.bmcl.2004.06.028

  日期：2004.9

  exploit cyclophilin as a potential target for neurological drug design, we demonstrate in this presentation that several nonimmunosuppressant analogues of cyclosporin A, modified at the various positions in the 'effector' domain, are equipotent nerve growth agents compared to cyclosporin A. Our results suggest that neurotrophic activity of cyclosporin A and its derivatives resides in the binding domain

  为了利用亲环蛋白作为神经病学药物设计的潜在靶标，我们在本演示中证明了环孢菌素A的几种非免疫抑制剂类似物（在“效应子”域的各个位置进行了修饰）与环孢菌素A相比是等价的神经生长剂。结果表明，环孢菌素A及其衍生物的神经营养活性位于结合域中，并且与亲环蛋白的结合和/或抑制旋转异构酶活性可能是亲环蛋白配体神经营养作用的必要条件。
• Total Synthesis of Cyclosporine: Access to N-Methylated Peptides via Isonitrile Coupling Reactions
  作者：Xiangyang Wu、Jennifer L. Stockdill、Ping Wang、Samuel J. Danishefsky

  DOI：10.1021/ja100517v

  日期：2010.3.31

  tertiary amide bond formations have been applied to a novel total synthesis of the important cyclic polypeptide cyclosporine A. Specifically, the disclosed synthetic route demonstrates the utility of microwave-mediated carboxylic acid isonitrile couplings, thioacid isonitrile couplings at ambient temperature, and isonitrile-mediated couplings of carboxylic acids and thioacids with amines to form challenging

  使用异腈提供仲和叔酰胺键形成的最新进展已应用于重要环状多肽环孢菌素 A 的新型全合成。 具体而言，所公开的合成路线证明了微波介导的羧酸异腈偶联、硫代酸的效用环境温度下的异腈偶联，以及异腈介导的羧酸和硫代酸与胺的偶联以形成具有挑战性的酰胺键。
• COLUCCI, WILLIAM J.;TUNG, ROGER D.;PETRI, JOHN A.;RICH, DANIEL H., J. ORG. CHEM., 55,(1990) N, C. 2895-2903
  作者：COLUCCI, WILLIAM J.、TUNG, ROGER D.、PETRI, JOHN A.、RICH, DANIEL H.

  DOI：——

  日期：——