pentafluorophenyl (2S,3S)-3-<(tert-butyldimethylsilyl)oxy>-2--N-methylamino>-3-(4-iodophenyl)propionate | 161634-95-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: pentafluorophenyl (2S,3S)-3-<(tert-butyldimethylsilyl)oxy>-2--N-methylamino>-3-(4-iodophenyl)propionate
• 英文别名: (2,3,4,5,6-pentafluorophenyl) (2S,3S)-3-[tert-butyl(dimethyl)silyl]oxy-3-(4-iodophenyl)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoate
• CAS: 161634-95-3
• 化学式: C₂₇H₃₃F₅INO₅Si
• 分子量: 701.545
• InChiKey: NOZKYQFQDDQJSE-VXKWHMMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.89
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N,O⁴-dimethyl-L-DOPA methyl ester 、 pentafluorophenyl (2S,3S)-3-<(tert-butyldimethylsilyl)oxy>-2--N-methylamino>-3-(4-iodophenyl)propionate 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 以67%的产率得到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
  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：

  (2S,3S)-3-hydroxy-3-(4-iodophenyl)-2-(methylamino)propionic acid 在 咪唑 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 61.0h， 生成 pentafluorophenyl (2S,3S)-3-<(tert-butyldimethylsilyl)oxy>-2--N-methylamino>-3-(4-iodophenyl)propionate
  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