(2S,8S)-5-oxo-2,8-bis-N-[9-(9-phenylfluorenyl)amino]azelate | 185121-50-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (2S,8S)-5-oxo-2,8-bis-N-[9-(9-phenylfluorenyl)amino]azelate
• 英文别名: (2S,8S)-5-oxo-2,8-bis[(9-phenylfluoren-9-yl)amino]nonanedioic acid
• CAS: 185121-50-0
• 化学式: C₄₇H₄₀N₂O₅
• 分子量: 712.845
• InChiKey: PXAMPLQKDPSUSJ-MJPWBCPGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  54
• 可旋转键数：
  14
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,8S)-5-oxo-2,8-bis-N-[9-(9-phenylfluorenyl)amino]azelate 在 氢气 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 53.0h， 生成 (3s,6s,8as)-6-[(叔丁氧基羰基)氨基]-5-氧代八氢吲哚嗪-3-羧酸甲酯
  参考文献：
  名称：

  Rigid Dipeptide Mimetics:  Efficient Synthesis of Enantiopure Indolizidinone Amino Acids

  摘要：

  An effective means to synthesize indolizidinone amino acids has been developed and furnishes all possible stereoisomers of these conformationally rigid mimetics of peptide secondary structures. Inexpensive glutamic acid was employed as chiral educt in a Claisen condensation/reductive amination/lactam cyclization sequence that furnished stereoselectively azabicyclo[3.4.0]alkane amino acid 1. Enantiopure (3S,6S,9S)- and (3R,6R,9R)-2-oxo-3-N-(BOC)amino-1-azabicyclo[4.3.0]nonane-9-carboxylic acids ((3S,6S,9S)- and (3R,6R,9R)-1) were respectively synthesized from L- and D-N-(PhF)glutamates 2 (PhF = 9-(9-phenylfluorenyl)). Slow addition of sodium bis(trimethylsilyl)amide to 2 provided good to excellent yields of beta-keto esters 3, which were subsequently hydrolyzed and decarboxylated to give symmetric alpha,omega-bis[N-(PhF)amino]azelate delta-ketones 5. Augmentation of hydrogen pressure increased diastereoselectivity in reductive aminations with 5 and afforded 5-alkylprolines 8 and 10. Lactam formation on exposure of 10 to triethylamine and N-protection with di-tert-butyl dicarbonate gave methyl 2-oxo-3-[N-(BOC)amino]-1-azabicyclo[4.3.0]nonane-9-carboxylate (12) which on C-terminal ester hydrolysis with hydroxide ion gave enantiopure [N-(BOC)amino]indolizidinone acid 1. Alternatively, hydride addition to ketone 5a gave symmetric alpha,omega-bis[N-(PhF)amino]azelate delta-alcohol 7a, which upon mesylation, and intramolecular S(N)2 displacement by the PhF amine gave specifically cis-5-alkylproline 15 that was similarly converted to (3S,6S,9S)-1. In addition, epimerization of the C-9 stereocenter of (3S,6S,9S)-[N-(BOC)amino]-indolizidinone methyl ester 12 with NaN(SiMe(3))(2) and ester hydrolysis gave (3S,6S,9R)-indolizidinone amino acid (3S,6S,9R)-1. By providing efficient methodology for synthesizing all of the possible stereoisomers of enantiopure indolizidinone amino acid 1, our route is specifically designed to enhance the general use of these peptide mimetics in the exploration of conformation-activity relationships of various biologically active peptides.

  DOI：

  10.1021/jo961872f
• 作为产物：
  描述：

  (2S,8S)-4-Methoxycarbonyl-5-oxo-2,8-bis-(9-phenyl-9H-fluoren-9-ylamino)-nonanedioic acid dimethyl ester 在 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 以78%的产率得到(2S,8S)-5-oxo-2,8-bis-N-[9-(9-phenylfluorenyl)amino]azelate
  参考文献：
  名称：

  Rigid Dipeptide Mimetics:  Efficient Synthesis of Enantiopure Indolizidinone Amino Acids

  摘要：

  An effective means to synthesize indolizidinone amino acids has been developed and furnishes all possible stereoisomers of these conformationally rigid mimetics of peptide secondary structures. Inexpensive glutamic acid was employed as chiral educt in a Claisen condensation/reductive amination/lactam cyclization sequence that furnished stereoselectively azabicyclo[3.4.0]alkane amino acid 1. Enantiopure (3S,6S,9S)- and (3R,6R,9R)-2-oxo-3-N-(BOC)amino-1-azabicyclo[4.3.0]nonane-9-carboxylic acids ((3S,6S,9S)- and (3R,6R,9R)-1) were respectively synthesized from L- and D-N-(PhF)glutamates 2 (PhF = 9-(9-phenylfluorenyl)). Slow addition of sodium bis(trimethylsilyl)amide to 2 provided good to excellent yields of beta-keto esters 3, which were subsequently hydrolyzed and decarboxylated to give symmetric alpha,omega-bis[N-(PhF)amino]azelate delta-ketones 5. Augmentation of hydrogen pressure increased diastereoselectivity in reductive aminations with 5 and afforded 5-alkylprolines 8 and 10. Lactam formation on exposure of 10 to triethylamine and N-protection with di-tert-butyl dicarbonate gave methyl 2-oxo-3-[N-(BOC)amino]-1-azabicyclo[4.3.0]nonane-9-carboxylate (12) which on C-terminal ester hydrolysis with hydroxide ion gave enantiopure [N-(BOC)amino]indolizidinone acid 1. Alternatively, hydride addition to ketone 5a gave symmetric alpha,omega-bis[N-(PhF)amino]azelate delta-alcohol 7a, which upon mesylation, and intramolecular S(N)2 displacement by the PhF amine gave specifically cis-5-alkylproline 15 that was similarly converted to (3S,6S,9S)-1. In addition, epimerization of the C-9 stereocenter of (3S,6S,9S)-[N-(BOC)amino]-indolizidinone methyl ester 12 with NaN(SiMe(3))(2) and ester hydrolysis gave (3S,6S,9R)-indolizidinone amino acid (3S,6S,9R)-1. By providing efficient methodology for synthesizing all of the possible stereoisomers of enantiopure indolizidinone amino acid 1, our route is specifically designed to enhance the general use of these peptide mimetics in the exploration of conformation-activity relationships of various biologically active peptides.

  DOI：

  10.1021/jo961872f

文献信息

• Selective <i>tert</i>-Butyl Ester Deprotection in the Presence of Acid Labile Protecting Groups with Use of ZnBr₂
  作者：Ramesh Kaul、Yann Brouillette、Zohreh Sajjadi、Karl A. Hansford、William D. Lubell

  DOI：10.1021/jo0491206

  日期：2004.9.1

  hydrolysis of tert-butyl esters in the presence of other acid-labile groups has been explored by employing α-amino esters and ZnBr2 in DCM. Although N-Boc and N-trityl groups were found to be labile, PhF protected amines were compatible with these Lewis acid deprotection conditions such that a variety of N-(PhF)amino acids were prepared in good yields from their corresponding tert-butyl esters.

  通过在DCM中使用α-氨基酯和ZnBr 2，探索了在其他酸不稳定基团存在下叔丁基酯的化学选择性水解。尽管发现N -Boc和N-三苯甲基不稳定，但PhF保护的胺与这些路易斯酸脱保护条件兼容，因此可以从其相应的叔丁基酯中以高收率制备各种N-（PhF）氨基酸。