(9S,12S,13S)-13-(tert-Butyl-dimethyl-silanyloxy)-4-methoxy-10-methyl-12-methylamino-11-oxo-2-oxa-10-aza-tricyclo[12.2.2.1^3,7]nonadeca-1(17),3,5,7(19),14(18),15-hexaene-9-carboxylic acid methyl ester | 161635-01-4

• 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: (9S,12S,13S)-13-(tert-Butyl-dimethyl-silanyloxy)-4-methoxy-10-methyl-12-methylamino-11-oxo-2-oxa-10-aza-tricyclo[12.2.2.1^3,7]nonadeca-1(17),3,5,7(19),14(18),15-hexaene-9-carboxylic acid methyl ester
• CAS: 161635-01-4
• 化学式: C₂₈H₄₀N₂O₆Si
• 分子量: 528.721
• InChiKey: WAYGDMXLWUHACR-TUSQITKMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.69
• 重原子数：
  37.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  86.33
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (9S,12S,13S)-13-(tert-Butyl-dimethyl-silanyloxy)-4-methoxy-10-methyl-12-methylamino-11-oxo-2-oxa-10-aza-tricyclo[12.2.2.1^3,7]nonadeca-1(17),3,5,7(19),14(18),15-hexaene-9-carboxylic acid methyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 75.5h， 生成
  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：

  methyl 13(S)-<(tert-butyldimethylsilyl)oxy>-12(S)--N-methylamino>-4-methoxy-10-methyl-11-oxo-10-aza-2-oxatricyclo<12.2.2.1^3,7>nonadeca-3,5,7(19),14,16,17-hexaene-9(S)-carboxylate 在 叔丁基二甲硅基三氟甲磺酸酯 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (9S,12S,13S)-13-(tert-Butyl-dimethyl-silanyloxy)-4-methoxy-10-methyl-12-methylamino-11-oxo-2-oxa-10-aza-tricyclo[12.2.2.1^3,7]nonadeca-1(17),3,5,7(19),14(18),15-hexaene-9-carboxylic acid methyl ester
  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