1-O-tert-butyl 2-O-methyl (2S)-5-[(3S)-4-methoxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutyl]pyrrolidine-1,2-dicarboxylate | 185121-37-3

• 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: 1-O-tert-butyl 2-O-methyl (2S)-5-[(3S)-4-methoxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutyl]pyrrolidine-1,2-dicarboxylate
• CAS: 185121-37-3
• 化学式: C₂₁H₃₆N₂O₈
• 分子量: 444.525
• InChiKey: XRESLFMRINXNPY-FGRDXJNISA-N

物化性质

• 沸点：
  523.7±45.0 °C(Predicted)
• 密度：
  1.138±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  31
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-O-tert-butyl 2-O-methyl (2S)-5-[(3S)-4-methoxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutyl]pyrrolidine-1,2-dicarboxylate 在 盐酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以100%的产率得到
  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：

  1,3-丙酮二羧酸二乙酯 在 palladium on activated charcoal 、 Rh(I)(COD)(S,S) Et-DUPHOS 三氟化硼乙醚 、 氢气 、 二异丁基氢化铝 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 盐酸 、 甲醇 、 二氯甲烷 、 甲苯 、 苯 为溶剂， -78.0~20.0 ℃ 、482.63 kPa 条件下， 反应 84.17h， 生成 1-O-tert-butyl 2-O-methyl (2S)-5-[(3S)-4-methoxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutyl]pyrrolidine-1,2-dicarboxylate
  参考文献：
  名称：

  An efficient approach to asymmetric synthesis of dipeptide β-turn mimetics: indolizidinone amino acids

  摘要：

  Azabicyclo[X.Y.0] alkane amino acids are rigid dipeptide P-turn mimetics with great potential applications for drug discovery. The lack of efficient methods to synthesize these compounds is a major bottleneck in this field. Herein we report an efficient approach to the enantiopure synthesis of (3S,6S,9S) and (3R,6R,9R) methyl 2-oxo-3-[N-(Boc/Cbz)amino]-1-azabicyclo[4,3,0]nonane-9-carboxylates 1. In this approach, the key intermediates 5a and 5b with different stereochemical configurations were efficiently constructed from the same precursor in high stereoselectivity via asymmetric hydrogenations using (S,S) or (R,R) Et-DUPHOS, Rh(I)-based catalysts. The process, starting from inexpensive diethyl 1,3-acetonedicarboxylate 2, can allow for the practical synthesis of this class of compounds. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(01)00409-9