(2S,4S)-3,3-dimethyl-4-hydroxy-N-(9-phenylfluoren-9-yl)proline benzyl ester | 173913-65-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (2S,4S)-3,3-dimethyl-4-hydroxy-N-(9-phenylfluoren-9-yl)proline benzyl ester
• 英文别名: benzyl (2S,4S)-4-hydroxy-3,3-dimethyl-1-(9-phenylfluoren-9-yl)pyrrolidine-2-carboxylate
• CAS: 173913-65-0
• 化学式: C₃₃H₃₁NO₃
• 分子量: 489.614
• InChiKey: KRKCZWOUNSYJIS-LOYHVIPDSA-N

物化性质

• 沸点：
  608.2±55.0 °C(Predicted)
• 密度：
  1.229±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,4S)-3,3-dimethyl-4-hydroxy-N-(9-phenylfluoren-9-yl)proline benzyl ester 在 palladium dihydroxide 偶氮二异丁腈 、 氢气 、 三正丁基氢锡 、 sodium hydride 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 4.0 ℃ 、506.62 kPa 条件下， 反应 26.5h， 生成 (S)-N-Boc-3,3-二甲基吡咯烷-2-甲酸
  参考文献：
  名称：

  Regioselective Enolization and Alkylation of 4-Oxo-N-(9-phenylfluoren-9-yl)proline:  Synthesis of Enantiopure Proline−Valine and Hydroxyproline−Valine Chimeras

  摘要：

  The regioselective enolization of 4-oxo-N-(9-phenylfluoren-9-yl)proline benzyl ester (5) followed by alkylation with different alkyl halides has been used to synthesize a variety of beta-alkylproline derivatives. In particular, enolization of 5 with 400 mol % of KN(SiMe(3))(2) and alkylation with iodomethane provided 3,3-dimethyl-4-oxo-N-(9-phenylfluoren-9-yl)proline benzyl ester (7a) in excellent yield. Subsequent hydride reduction of ketone 7a and protecting group exchange by hydrogenation in the presence of di-tert-butyl dicarbonate provided enantiopure (2S,4R)- and (2S,4S)-3,3-dimethyl-4-hydroxy-N-(BOC)prolines. 2. Hydroxyproline-valine chimeras (2S,4R)- and (2S,4S)-2 are each synthesized from hydroxyproline in six steps and 27% respective overall yield. Deoxygenation of 3,3-dimethyl-4-hydroxy-N-(9-phenylfluoren-9-yl)proline benzyl esters 9 via their conversion to xanthates 10 followed by tributylstannane-mediated reduction provided 3,3-dimethyl-N-(9-phenylfluoren-9-yl)proline benzyl ester (11) in excellent yield. Hydrogenation of 11 with Pearlman's catalyst in the presence of di-tert-butyl dicarbonate then furnished (2S)-3,3-dimethyl-N-(BOC)proline (1) in the last step of an eight-step synthesis (41% overall yield) from hydroxyproline. Both proline-valine and hydroxyproline-valine chimeras 1 and 2 were designed to serve as tools for studying the conformational requirements of biologically active peptides.

  DOI：

  10.1021/jo9514984
• 作为产物：
  描述：

  (2S)-3,3-dimethyl-4-oxo-N-(9-phenylfluoren-9-yl)proline benzyl ester 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.5h， 以38%的产率得到(2S,4S)-3,3-dimethyl-4-hydroxy-N-(9-phenylfluoren-9-yl)proline benzyl ester
  参考文献：
  名称：

  Regioselective Enolization and Alkylation of 4-Oxo-N-(9-phenylfluoren-9-yl)proline:  Synthesis of Enantiopure Proline−Valine and Hydroxyproline−Valine Chimeras

  摘要：

  The regioselective enolization of 4-oxo-N-(9-phenylfluoren-9-yl)proline benzyl ester (5) followed by alkylation with different alkyl halides has been used to synthesize a variety of beta-alkylproline derivatives. In particular, enolization of 5 with 400 mol % of KN(SiMe(3))(2) and alkylation with iodomethane provided 3,3-dimethyl-4-oxo-N-(9-phenylfluoren-9-yl)proline benzyl ester (7a) in excellent yield. Subsequent hydride reduction of ketone 7a and protecting group exchange by hydrogenation in the presence of di-tert-butyl dicarbonate provided enantiopure (2S,4R)- and (2S,4S)-3,3-dimethyl-4-hydroxy-N-(BOC)prolines. 2. Hydroxyproline-valine chimeras (2S,4R)- and (2S,4S)-2 are each synthesized from hydroxyproline in six steps and 27% respective overall yield. Deoxygenation of 3,3-dimethyl-4-hydroxy-N-(9-phenylfluoren-9-yl)proline benzyl esters 9 via their conversion to xanthates 10 followed by tributylstannane-mediated reduction provided 3,3-dimethyl-N-(9-phenylfluoren-9-yl)proline benzyl ester (11) in excellent yield. Hydrogenation of 11 with Pearlman's catalyst in the presence of di-tert-butyl dicarbonate then furnished (2S)-3,3-dimethyl-N-(BOC)proline (1) in the last step of an eight-step synthesis (41% overall yield) from hydroxyproline. Both proline-valine and hydroxyproline-valine chimeras 1 and 2 were designed to serve as tools for studying the conformational requirements of biologically active peptides.

  DOI：

  10.1021/jo9514984

文献信息

• Regioselective Enolization and Alkylation of 4-Oxo-<i>N</i>-(9-phenylfluoren-9-yl)proline:  Synthesis of Enantiopure Proline−Valine and Hydroxyproline−Valine Chimeras
  作者：Raman Sharma、William D. Lubell

  DOI：10.1021/jo9514984

  日期：1996.1.1

  The regioselective enolization of 4-oxo-N-(9-phenylfluoren-9-yl)proline benzyl ester (5) followed by alkylation with different alkyl halides has been used to synthesize a variety of beta-alkylproline derivatives. In particular, enolization of 5 with 400 mol % of KN(SiMe(3))(2) and alkylation with iodomethane provided 3,3-dimethyl-4-oxo-N-(9-phenylfluoren-9-yl)proline benzyl ester (7a) in excellent yield. Subsequent hydride reduction of ketone 7a and protecting group exchange by hydrogenation in the presence of di-tert-butyl dicarbonate provided enantiopure (2S,4R)- and (2S,4S)-3,3-dimethyl-4-hydroxy-N-(BOC)prolines. 2. Hydroxyproline-valine chimeras (2S,4R)- and (2S,4S)-2 are each synthesized from hydroxyproline in six steps and 27% respective overall yield. Deoxygenation of 3,3-dimethyl-4-hydroxy-N-(9-phenylfluoren-9-yl)proline benzyl esters 9 via their conversion to xanthates 10 followed by tributylstannane-mediated reduction provided 3,3-dimethyl-N-(9-phenylfluoren-9-yl)proline benzyl ester (11) in excellent yield. Hydrogenation of 11 with Pearlman's catalyst in the presence of di-tert-butyl dicarbonate then furnished (2S)-3,3-dimethyl-N-(BOC)proline (1) in the last step of an eight-step synthesis (41% overall yield) from hydroxyproline. Both proline-valine and hydroxyproline-valine chimeras 1 and 2 were designed to serve as tools for studying the conformational requirements of biologically active peptides.