(2S,8S)-di-tert-butyl 5-oxo-2,8-di-[N-(9-(9-phenylfluorenyl))amino]azelate | 159303-53-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (2S,8S)-di-tert-butyl 5-oxo-2,8-di-[N-(9-(9-phenylfluorenyl))amino]azelate
• 英文别名: ditert-butyl (2S,8S)-5-oxo-2,8-bis[(9-phenylfluoren-9-yl)amino]nonanedioate
• CAS: 159303-53-4
• 化学式: C₅₅H₅₆N₂O₅
• 分子量: 825.06
• InChiKey: QRQBEFGHNKXDDW-GTMCEHENSA-N

物化性质

• 沸点：
  900.4±65.0 °C(predicted)
• 密度：
  1.22±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  10.3
• 重原子数：
  62
• 可旋转键数：
  18
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,8S)-di-tert-butyl 5-oxo-2,8-di-[N-(9-(9-phenylfluorenyl))amino]azelate 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 生成 tert-butyl 5-[3-amino-4-[(2-methylpropan-2-yl)oxy]-4-oxobutyl]pyrrolidine-2-carboxylate
  参考文献：
  名称：

  Synthesis of Enantiopure .alpha.,.omega.-Diamino Dicarboxylates and Azabicycloalkane Amino Acids by Claisen Condensation of .alpha.-[N-(Phenylfluorenyl)amino] Dicarboxylates

  摘要：

  Enantiomerically pure (3S,6S,9S)-2-oxo-3-(N-BOC-amino)-1-azabicyclo[4.3.0]nonane-9-carboxylic acid ((3S,6S,9S)-1) was prepared in 39% overall yield from alpha-tert-butyl gamma-methyl N-(9-(9-phenylfluorenyl))glutamate (5) using a Claisen condensation/reductive amination/lactam cyclization sequence.

  DOI：

  10.1021/jo00100a008
• 作为产物：
  描述：

  (2S,4RS,8S)-di-tert-butyl 4-carbomethoxy-5-oxo-2,8-bisazelate 在 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 1.0h， 以99%的产率得到(2S,8S)-di-tert-butyl 5-oxo-2,8-di-[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

• Synthesis of Enantiopure 7-[3-Azidopropyl]indolizidin-2-one Amino Acid. A Constrained Mimic of the Peptide Backbone Geometry and Heteroatomic Side-Chain Functionality of the Ala-Lys Dipeptide
  作者：Zhe Feng、William D. Lubell

  DOI：10.1021/jo001252l

  日期：2001.2.1

  alcohol gave (2S,4R,8S)-di-tert-butyl 4-[3-tert-butyldimethylsiloxypropyl]-5-oxo-2,8-di-[N-(PhF)amino]azelate 9 as a pure diastereomer in 33% overall yield. Linear ketone 9 was then converted into the indolizidinone heterocycle by a route featuring reductive amination, lactam cyclization, and isolation by way of a silyl ether which provided the (6S,7R)-isomer of 11.

  对映纯N-（BOC）氨基-7- [3-叠氮丙基]吲哚并丁-2-酮酸1是通过用叠氮化钠置换其7-羟丙基对应物11的甲磺酸盐并随后进行酯水解而合成的。从（2S，8S）-二叔丁基5-氧代-2，8-的烷基化开始，得到N-（BOC）氨基-7- [3-羟丙基]吲哚并丁-2-酮酯11。二[N-（PhF）氨基]壬二酸酯5（PhF = 9-（9-苯基芴基））。5的立体选择性烯丙基化，区域选择性的烯烃氢硼化，选择性的伯醇保护作为甲硅烷基醚，以及仲醇的氧化得到（2S，4R，8S）-二叔丁基4- [3-叔丁基二甲基甲硅烷氧基丙基] -5-作为纯非对映异构体的oxo-2,8-二-[N-（N-（PhF）氨基]壬二酸酯9，总产率为33％。然后通过具有还原胺化作用的路线，将线性酮9转化为吲哚西酮酮杂环，
• 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。
• Rigid Dipeptide Mimics:  Synthesis of Enantiopure 5- and 7-Benzyl and 5,7-Dibenzyl Indolizidinone Amino Acids via Enolization and Alkylation of δ-Oxo α,ω-Di-[<i>N</i>-(9-(9-phenylfluorenyl))amino]azelate Esters
  作者：Felix Polyak、William D. Lubell

  DOI：10.1021/jo980596x

  日期：1998.8.1

  glutamic acid was employed as chiral educt in a Claisen condensation/ketone alkylation/reductive amination/lactam cyclization sequence that furnished alkyl-branched azabicyclo[4.3.0]alkane amino acid. Enantiopure 5-benzyl-, 7-benzyl-, and 5,7-dibenzylindolizidinone amino acids 2-4 were stereoselectively synthesized via efficient reaction sequences featuring the alkylation of di-tert-butyl alpha,omega-di

  Azabicyclo [XY0]烷烃氨基酸是用于构建肽结构模拟物和模板的工具，用于生成用于药物发现的组合库。我们已经详细阐述了合成这些构象刚性二肽的方法，以便可以将烷基附加到杂环上以生成肽骨架和侧链结构的模拟物。廉价的谷氨酸​​用作克莱森缩合/酮烷基化/还原胺化/内酰胺环化序列的手性离析物，提供了烷基支链的氮杂双环[4.3.0]烷烃氨基酸。通过特征在于二叔丁基α，ω-二-[N-（PhF）的烷基化的有效反应序列，立体选择性地合成了对映体5-苄基，7-苄基和5,7-二苄基吲哚并二酮氨基酸2-4氨基]壬二酸酯δ-酮5。然后用氢氧根离子和三甲基硅烷醇钾酯水解，得到对映体纯的吲哚齐酮酮氨基酸2-4。苄基吲哚并二酮氨基酯在C-9处的差向异构化也可用于提供10、11和14的替代非对映异构体。这种通过区域选择性和非对映选择性控制将侧链基团引入杂环的实用方法旨在增强烷基-烷基的使用。支链氮杂双环烷烃氨基酸，
• Rigid Dipeptide Mimetics:  Efficient Synthesis of Enantiopure Indolizidinone Amino Acids
  作者：Henry-Georges Lombart、William D. Lubell

  DOI：10.1021/jo961872f

  日期：1996.1.1

  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.
• Synthesis of Enantiopure .alpha.,.omega.-Diamino Dicarboxylates and Azabicycloalkane Amino Acids by Claisen Condensation of .alpha.-[N-(Phenylfluorenyl)amino] Dicarboxylates
  作者：Henry-Georges Lombart、William D. Lubell

  DOI：10.1021/jo00100a008

  日期：1994.10

  Enantiomerically pure (3S,6S,9S)-2-oxo-3-(N-BOC-amino)-1-azabicyclo[4.3.0]nonane-9-carboxylic acid ((3S,6S,9S)-1) was prepared in 39% overall yield from alpha-tert-butyl gamma-methyl N-(9-(9-phenylfluorenyl))glutamate (5) using a Claisen condensation/reductive amination/lactam cyclization sequence.