L-α-tert-butyl γ-methyl N-(9-(9-phenylfluorenyl))glutamate | 119595-73-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: L-α-tert-butyl γ-methyl N-(9-(9-phenylfluorenyl))glutamate
• 英文别名: α-tert-butyl γ-methyl N-[9-(9-phenylfluorenyl)]glutamate；1-O-tert-butyl 5-O-methyl (2S)-2-[(9-phenylfluoren-9-yl)amino]pentanedioate
• CAS: 119595-73-2
• 化学式: C₂₉H₃₁NO₄
• 分子量: 457.569
• InChiKey: LTHPVYYZQFOAEW-VWLOTQADSA-N

物化性质

• 熔点：
  100 °C
• 沸点：
  575.1±50.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  L-α-tert-butyl γ-methyl N-(9-(9-phenylfluorenyl))glutamate 在 lithium aluminium tetrahydride 、 四溴化碳 、 双(三甲基硅烷基)氨基钾 、 N,N-二异丙基乙胺 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 27.0h， 生成 (4S)-4-甲基-l-脯氨酸
  参考文献：
  名称：

  Synthesis of 4-substituted prolines as conformationally constrained amino acid analogs

  摘要：

  DOI：

  10.1021/jo00269a022
• 作为产物：
  描述：

  9-溴-9-苯基芴 在 三甲基氯硅烷 、 lead(II) nitrate 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 生成 L-α-tert-butyl γ-methyl N-(9-(9-phenylfluorenyl))glutamate
  参考文献：
  名称：

  Mulzer, Johann; Schroeder, Fridtjof; Lobbia, Alessandro, Angewandte Chemie, 1994, vol. 106, # 17, p. 1813 - 1815

  摘要：

  DOI：

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。
• Potentially Macrocyclic Peptidyl Boronic Acids as Chymotrypsin Inhibitors
  作者：Zong-Qiang Tian、Bradley B. Brown、David P. Mack、Craig A. Hutton、Paul A. Bartlett

  DOI：10.1021/jo9615007

  日期：1997.2.1

  with the complex boronic acid analogs 7, 8-OH, and 8-NH(2)(). In these structures, the P(1) and P(2) residues and the P(1)'-P(3)' residues are connected through the P(2) and P(1)' side chains, to encourage formation of the diester or amide-ester adducts via macrocyclization. These inhibitors were assembled from suitably protected derivatives of 2,4-diaminobutanoic acid or 2,4-diaminopentanoic acid

  用复杂的硼酸类似物7、8-OH和8-NH（2）（）探索了在丝氨酸蛋白酶活性位点形成肽硼酸酯加合物的可能性，该位点模仿肽水解机理中的第一个四面体中间体。在这些结构中，P（1）和P（2）残基以及P（1）'-P（3）'残基通过P（2）和P（1）'侧链连接，以鼓励形成经由大环化的二酯或酰胺酯加合物。这些抑制剂由2，4-二氨基丁酸或2，4-二氨基戊酸（11），硼苯丙氨酸（12），天冬氨酸，苹果酸或取代的苹果酸类似物13和Leu-Arg二肽的适当保护的衍生物组装而成。为（S，S）-2，4-二氨基戊酸酯11和（S，S）-β-异丁基苹果酸酯13衍生物开发了立体选择性合成。复杂的硼酸肽基酯7（K（i）= 26 nM）和8-OH（68 nM）是α-胰凝乳蛋白酶的有效抑制剂。然而，7的亲和力既不依赖于时间，也不依赖于pH值，仅适度地大于8-H（114 nM），9（356 nM）和10（219 nM）不能比较的比较化合物。环化或形成二酯加合物。
• An Olefination Entry for the Synthesis of Enantiopure α,ω-Diaminodicarboxylates and Azabicyclo[<i>X</i>.<i>Y</i>.0]alkane Amino Acids
  作者：Francis Gosselin、William D. Lubell

  DOI：10.1021/jo9814602

  日期：1998.10.1

  beta-keto phosphonates 21-23. The power of this approach for making azabicyclo[X.Y.0]alkane amino acid was then illustrated by the first synthesis of enantiopure indolizidin-9-one amino acid 2 in nine steps and >25% overall yield from inexpensive aspartic acid as chiral educt. Hydrogenation of (2S,8S)-di-tert-butyl 4-oxo-2,8-bis[N-(PhF)amino]non-4-enedioate (24) in 9:1 EtOH:AcOH furnished a 9:1 diastereomeric

  合成各种链长的α，ω-二氨基二羧酸酯的新方法为制备一系列不同环尺寸的氮杂双环[XY0]烷烃氨基酸开辟了道路。通过将二甲基甲基膦酸锂阴离子加到α-叔丁基N-（PhF）天冬氨酸3，谷氨酸9和α-叔丁基的ω-甲基酯中，以71-90％的产率合成β-酮膦酸酯21-23氨基己二酸酯12（PhF = 9-苯基芴-9-基）。α-叔丁基N-（PhF）天门冬氨酸β-醛（5）的霍纳-沃兹沃思-埃蒙斯烯化反应制备了9至11个碳链长度的α，ω-二氨基二羧酸24-26，产率为78-87％氨基二羧酸酯衍生的β-酮膦酸酯21-23。这种方法的作用是制造氮杂双环[XY 然后，通过九个步骤的对映纯纯的吲哚izidin-9-一个氨基酸2的首次合成和廉价的天冬氨酸作为手性离析物的总收率> 25％，来说明[0]烷烃氨基酸。在9：1的EtOH：AcOH中氢化（2S，8S）-二叔丁基4-oxo-2,8-双[N-（PhF）氨基]非-4-烯二酸酯（24）
• Biosynthesis of 4-Methylproline in Cyanobacteria:  Cloning of <i>n</i><i>osE</i> and <i>n</i><i>osF</i> Genes and Biochemical Characterization of the Encoded Dehydrogenase and Reductase Activities
  作者：Hendrik Luesch、Dietmar Hoffmann、Joan M. Hevel、Julia E. Becker、Trimurtulu Golakoti、Richard E. Moore

  DOI：10.1021/jo026479q

  日期：2003.1.1

  The biosynthesis of the unusual amino acid 4-methylproline in the Nostoc genus of cyanobacteria was investigated on the genetic and enzymatic level. Two genes involved in the biosynthesis were cloned and the corresponding enzymes, a zinc-dependent long-chain dehydrogenase and a Delta(1)-pyrroline-5-carboxylic acid (P5C) reductase homologue, were overexpressed in Escherichia coli and biochemically characterized. Putative substrates were synthesized to test enzyme substrate specificities, and deuterium labeling studies were carried out to reveal the stereospecificities of the enzymatic reactions with respect to the substrates as well as to the coenzymes.
• 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.