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 | 160480-12-6

• 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: 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
• 英文别名: methyl (9S,12S,13S)-13-[tert-butyl(dimethyl)silyl]oxy-4-methoxy-10-methyl-12-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-11-oxo-2-oxa-10-azatricyclo[12.2.2.13,7]nonadeca-1(16),3,5,7(19),14,17-hexaene-9-carboxylate
• CAS: 160480-12-6
• 化学式: C₃₃H₄₈N₂O₈Si
• 分子量: 628.838
• InChiKey: MRGPJMROOWVCPY-WIRXVTQYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.34
• 重原子数：
  44
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  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 盐酸 、 lithium hydroxide 、 叔丁基二甲硅基三氟甲磺酸酯 、 乙酸乙酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 54.0h， 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：

  3-hydroxy-N,O⁴-dimethyl-N-<3(S)-<(tert-butyldimethylsilyl)oxy>-N-<(tert-butyloxy)carbonyl>-N-methyl-4'-iodo-L-phenylalanyl>-L-tyrosine methyl ester 在 2,6-二甲基吡啶 、 sodium hydride 作用下， 生成 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
  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

• 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.