(6S,9R,15S,18R)-methyl 9,18-diallyl-15-benzyl-6-(4-hydroxybenzyl)-2,2-dimethyl-4,7,10,13,16-pentaoxo-3-oxa-5,8,11,14,17-pentaazanonadecan-19-oate | 944918-33-6

• 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: (6S,9R,15S,18R)-methyl 9,18-diallyl-15-benzyl-6-(4-hydroxybenzyl)-2,2-dimethyl-4,7,10,13,16-pentaoxo-3-oxa-5,8,11,14,17-pentaazanonadecan-19-oate
• 英文别名: Boc-Tyr-D-Gly(allyl)-Gly-Phe-D-Gly(allyl)-OMe；methyl (2R)-2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]pent-4-enoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]pent-4-enoate
• CAS: 944918-33-6
• 化学式: C₃₆H₄₇N₅O₉
• 分子量: 693.797
• InChiKey: ITWRXBBYVUYPJK-GKQHHHCTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  50
• 可旋转键数：
  21
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  201
• 氢给体数：
  6
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (6S,9R,15S,18R)-methyl 9,18-diallyl-15-benzyl-6-(4-hydroxybenzyl)-2,2-dimethyl-4,7,10,13,16-pentaoxo-3-oxa-5,8,11,14,17-pentaazanonadecan-19-oate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 N-tert-butyloxycarbonyl-L-tyrosinyl-D-allylglycyl-glycyl-L-phenylalanyl-D-allylglycine-OH
  参考文献：
  名称：

  Synthesis of Stable and Potent δ/μ Opioid Peptides:  Analogues of H-Tyr-c[d-Cys-Gly-Phe-d-Cys]-OH by Ring-Closing Metathesis

  摘要：

  Ring-closing metathesis has emerged as a powerful tool in organic synthesis for generating cyclic structures via C-C double bond formation. Recently, it has been successfully used in peptide chemistry for obtaining cyclic molecules bridged through an olefin unit in place of the usual disulfide bond. Here, we describe this approach for obtaining cyclic olefin bridged analogues of H-Tyr-c[D-Cys-Gly-Phe-Cys]-OH. The synthesis of the new ligands was performed using the second generation Grubbs' catalyst. The resulting cis-8 (cDADAE) and trans-9 (tDADAE) were fully characterized and tested at delta, mu, and kappa opioid receptors. Also the linear precursor 13 (lDADAE) and the hydrogenated derivative 11(rDADAE) also were tested. All the cyclic products containing a olefinic bond are slightly selective but highly active and potent for the delta and mu opioid receptors. Activity toward the kappa opioid receptors was absent or very low.

  DOI：

  10.1021/jm061048b
• 作为产物：
  描述：

  、 Boc-L-酪氨酸 在 N-甲基吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (6S,9R,15S,18R)-methyl 9,18-diallyl-15-benzyl-6-(4-hydroxybenzyl)-2,2-dimethyl-4,7,10,13,16-pentaoxo-3-oxa-5,8,11,14,17-pentaazanonadecan-19-oate
  参考文献：
  名称：

  Synthesis of Stable and Potent δ/μ Opioid Peptides:  Analogues of H-Tyr-c[d-Cys-Gly-Phe-d-Cys]-OH by Ring-Closing Metathesis

  摘要：

  Ring-closing metathesis has emerged as a powerful tool in organic synthesis for generating cyclic structures via C-C double bond formation. Recently, it has been successfully used in peptide chemistry for obtaining cyclic molecules bridged through an olefin unit in place of the usual disulfide bond. Here, we describe this approach for obtaining cyclic olefin bridged analogues of H-Tyr-c[D-Cys-Gly-Phe-Cys]-OH. The synthesis of the new ligands was performed using the second generation Grubbs' catalyst. The resulting cis-8 (cDADAE) and trans-9 (tDADAE) were fully characterized and tested at delta, mu, and kappa opioid receptors. Also the linear precursor 13 (lDADAE) and the hydrogenated derivative 11(rDADAE) also were tested. All the cyclic products containing a olefinic bond are slightly selective but highly active and potent for the delta and mu opioid receptors. Activity toward the kappa opioid receptors was absent or very low.

  DOI：

  10.1021/jm061048b

文献信息

• In Situ Methylene Capping: A General Strategy for Efficient Stereoretentive Catalytic Olefin Metathesis. The Concept, Methodological Implications, and Applications to Synthesis of Biologically Active Compounds
  作者：Chaofan Xu、Xiao Shen、Amir H. Hoveyda

  DOI：10.1021/jacs.7b06552

  日期：2017.8.9

  catalyst-controlled stereoselective olefin metathesis considerably. By incorporation of commercially available Z-butene together with robust and readily accessible Ru-based dithiolate catalysts developed in these laboratories, a large variety of transformations can be made to proceed with terminal alkenes, without the need for a priori synthesis of a stereochemically defined disubstituted olefin. Reactions thus proceed

  原位亚甲基封端作为一种实用且广泛适用的策略被引入，可以显着扩大催化剂控制的立体选择性烯烃复分解的范围。通过将市售的 Z-丁烯与这些实验室开发的坚固且易于获得的基于 Ru 的二硫醇催化剂结合，可以进行多种转化以处理末端烯烃，而无需先验合成立体化学定义的双取代烯烃。因此，与使用其他基于 Ru、Mo 或 W 的配合物相比，反应以显着更高的效率和 Z 选择性进行。与含有羧酸、醛、烯丙醇、芳基烯烃、α取代基的烯烃交叉复分解，或氨基酸残基以 47-88% 的产率和 90:10 至 >98:2 的 Z:E 选择性生成所需产物。使用 70:30 Z-:E-丁烯混合物（原油裂解的副产品），转化同样有效且具有立体选择性。原位亚甲基封端策略与相同的儿茶酚硫醇配合物（无需催化剂修饰）一起进行闭环复分解反应，以 40-70% 的产率和 96:4-98 的产率生成 14 至 21 元环大环烯烃:2 Z:E 选择性；与
• [EN] METHOD OF MAKING A CROSS METATHESIS PRODUCT<br/>[FR] PROCÉDÉ DE FABRICATION D'UN PRODUIT DE MÉTATHÈSE CROISÉE
  申请人：TRUSTEES BOSTON COLLEGE

  公开号：WO2019018773A1

  公开（公告）日：2019-01-24

  Method of making a cross metathesis product, the method comprising at least step (X) or step (Y): (X) reacting in a cross metathesis reaction a first compound comprising a terminal olefinic group with a second compound comprising a terminal olefinic group, wherein the first and the second compound may be identical or may be different from one another; or (Y) reacting in a ring-closing metathesis reaction two terminal olefinic groups which are comprised in a third compound; wherein the reacting in step (X) or step (Y) is performed in the presence of a ruthenium carbene complex comprising a [Ru=C]-moiety and an internal olefin.

  制备交叉甲醇酯产物的方法，该方法包括至少步骤（X）或步骤（Y）：（X）在交叉甲醇酯反应中，将含有端烯基团的第一化合物与含有端烯基团的第二化合物反应，其中第一和第二化合物可以相同也可以不同；或（Y）在环闭合甲醇酯反应中，将包含在第三化合物中的两个端烯基团反应；在步骤（X）或步骤（Y）中的反应是在存在包含[Ru=C]-基团和内烯烃的钌卡宾配合物的情况下进行的。
• METHOD OF MAKING A CROSS METATHESIS PRODUCT
  申请人：Trustees of Boston College

  公开号：US20200123197A1

  公开（公告）日：2020-04-23

  Method of making a cross metathesis product, the method comprising at least step (X) or step (Y): (X) reacting in a cross metathesis reaction a first compound comprising a terminal olefinic group with a second compound comprising a terminal olefinic group, wherein the first and the second compound may be identical or may be different from one another; or (Y) reacting in a ring-closing metathesis reaction two terminal olefinic groups which are comprised in a third compound; wherein the reacting in step (X) or step (Y) is performed in the presence of a ruthenium carbene complex comprising a [Ru═C]-moiety and an internal olefin.