O-methylbouvardin | 110774-02-2

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物
• 英文名称: O-methylbouvardin
• 英文别名: 6-O-methylbouvardin；(1S,4R,7S,10S,13S,16S,17S)-17-hydroxy-24-methoxy-10-[(4-methoxyphenyl)methyl]-4,7,9,13,15,29-hexamethyl-22-oxa-3,6,9,12,15,29-hexazatetracyclo[14.12.2.218,21.123,27]tritriaconta-18,20,23,25,27(31),32-hexaene-2,5,8,11,14,30-hexone
• CAS: 110774-02-2
• 化学式: C₄₁H₅₀N₆O₁₀
• 分子量: 786.882
• InChiKey: BVLKHUDGMCRYQG-OCSOIWPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  57
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  196
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  O-methylbouvardin 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以86%的产率得到波凡霉素
  参考文献：
  名称：

  Total Synthesis of Bouvardin, O-Methylbouvardin, and O-Methyl-N9-desmethylbouvardin

  摘要：

  Concise total syntheses of bouvardin (1) and O-methylbouvardin (2) are described based on the asymmetric synthesis of the N-methyl-erythro-beta-hydroxy-L-4-iodophenylalanine derivative 24, its coupling with the selectively protected N,O-4-dimethyl-L-DOPA methyl ester to provide 40, and subsequent incorporation into a surprisingly successful key Ullmann macrocyclization reaction for preparation of the 14-membered 13 (S)-hydroxycycloisodityrosine subunit 15 of the bicyclic hexapeptides. Coupling of 15 with BOCNH-D-Ala-Ala-NMe-Tyr(OMe)-Ala-OC6F5 followed by 18-membered-ring macrocyclization strategically conducted with formation of a secondary amide at a D-amino acid amine terminus (C-2-N-3 amide) provided O-methylbouvardin (2). Selective demethylation (BBr3) of 2 provided bouvardin (1) in excellent conversion (86%). The extensions of the studies to the preparation of O-methyl-N-9-desmethylbouvardin (51) are detailed and its solution-phase conformational properties examined by H-1 NMR in efforts which confirm that the additional minor conformation of 1 and 2 (ca. 10-15%) observed in nonpolar solvents (CDCl3, THF-d(8)), arise from a cis N-9-C-8 N-methylamide conformation.

  DOI：

  10.1021/ja00098a015
• 作为产物：
  描述：

  BOC-D-Ala-L-Ala-NMe-L-Tyr(OMe)-L-Ala-OC6F5 在 盐酸 、 lithium hydroxide 、 二苯基磷酸 、 碳酸氢钠 、 乙酸乙酯 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 148.0h， 生成 O-methylbouvardin
  参考文献：
  名称：

  Total Synthesis of Bouvardin, O-Methylbouvardin, and O-Methyl-N9-desmethylbouvardin

  摘要：

  Concise total syntheses of bouvardin (1) and O-methylbouvardin (2) are described based on the asymmetric synthesis of the N-methyl-erythro-beta-hydroxy-L-4-iodophenylalanine derivative 24, its coupling with the selectively protected N,O-4-dimethyl-L-DOPA methyl ester to provide 40, and subsequent incorporation into a surprisingly successful key Ullmann macrocyclization reaction for preparation of the 14-membered 13 (S)-hydroxycycloisodityrosine subunit 15 of the bicyclic hexapeptides. Coupling of 15 with BOCNH-D-Ala-Ala-NMe-Tyr(OMe)-Ala-OC6F5 followed by 18-membered-ring macrocyclization strategically conducted with formation of a secondary amide at a D-amino acid amine terminus (C-2-N-3 amide) provided O-methylbouvardin (2). Selective demethylation (BBr3) of 2 provided bouvardin (1) in excellent conversion (86%). The extensions of the studies to the preparation of O-methyl-N-9-desmethylbouvardin (51) are detailed and its solution-phase conformational properties examined by H-1 NMR in efforts which confirm that the additional minor conformation of 1 and 2 (ca. 10-15%) observed in nonpolar solvents (CDCl3, THF-d(8)), arise from a cis N-9-C-8 N-methylamide conformation.

  DOI：

  10.1021/ja00098a015

文献信息

• Rubiaceae-Type Cyclopeptides from <i>Galianthe thalictroides</i>
  作者：Patrícia O. Figueiredo、Maria de Fatima C. Matos、Renata T. Perdomo、Wilson H. Kato、Marcos Vinícius G. O. Barros、Fernanda R. Garcez、Walmir S. Garcez

  DOI：10.1021/acs.jnatprod.5b00849

  日期：2016.4.22

  Two Rubiaceae-type cyclopeptides, 6-O-methylbouvardin (1) and the new cyclopeptide 5 beta-hydroxy-RA-III (2), were isolated from the roots of Galianthe thalictroides. Employing the sulforhodamine B assay, compounds 1 and 2 were tested in vitro against three cancer cell lines-786-0 (kidney carcinoma), PC-3 (prostate carcinoma), and HT-29 (colon carcinoma)-and showed GI(50) values ranging from 0.06 to 1.80 mu g mL(-1). This is the first report on the isolation of Rubiaceae-type cyclopeptides from a genus other than Rubia or Bouvardia.
• Total Synthesis of Bouvardin, O-Methylbouvardin, and O-Methyl-N9-desmethylbouvardin
  作者：Dale L. Boger、Michael A. Patane、Jiacheng Zhou

  DOI：10.1021/ja00098a015

  日期：1994.9

  Concise total syntheses of bouvardin (1) and O-methylbouvardin (2) are described based on the asymmetric synthesis of the N-methyl-erythro-beta-hydroxy-L-4-iodophenylalanine derivative 24, its coupling with the selectively protected N,O-4-dimethyl-L-DOPA methyl ester to provide 40, and subsequent incorporation into a surprisingly successful key Ullmann macrocyclization reaction for preparation of the 14-membered 13 (S)-hydroxycycloisodityrosine subunit 15 of the bicyclic hexapeptides. Coupling of 15 with BOCNH-D-Ala-Ala-NMe-Tyr(OMe)-Ala-OC6F5 followed by 18-membered-ring macrocyclization strategically conducted with formation of a secondary amide at a D-amino acid amine terminus (C-2-N-3 amide) provided O-methylbouvardin (2). Selective demethylation (BBr3) of 2 provided bouvardin (1) in excellent conversion (86%). The extensions of the studies to the preparation of O-methyl-N-9-desmethylbouvardin (51) are detailed and its solution-phase conformational properties examined by H-1 NMR in efforts which confirm that the additional minor conformation of 1 and 2 (ca. 10-15%) observed in nonpolar solvents (CDCl3, THF-d(8)), arise from a cis N-9-C-8 N-methylamide conformation.