(2S,5S,8aR)-2-(tert-Butoxycarbonylamino)-3-oxooctahydroindolizine-5-carboxylic acid | 215182-89-1

• 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: (2S,5S,8aR)-2-(tert-Butoxycarbonylamino)-3-oxooctahydroindolizine-5-carboxylic acid
• 英文别名: (2S,5S,8aR)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxo-2,5,6,7,8,8a-hexahydro-1H-indolizine-5-carboxylic acid
• CAS: 215182-89-1
• 化学式: C₁₄H₂₂N₂O₅
• 分子量: 298.339
• InChiKey: MXKPXSZDTOEKAN-UTLUCORTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-3-氨基-4-苯基丁酸苄酯盐酸盐 、 (2S,5S,8aR)-2-(tert-Butoxycarbonylamino)-3-oxooctahydroindolizine-5-carboxylic acid 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 (3S)-3-[[(2S)-2-[[(2S,5S,8aR)-3-oxo-2-[(2-phenylacetyl)amino]-2,5,6,7,8,8a-hexahydro-1H-indolizine-5-carbonyl]amino]-3-pyridin-3-ylpropanoyl]amino]-4-phenylbutanoic acid
  参考文献：
  名称：

  Targeting the Prostaglandin F2α Receptor for Preventing Preterm Labor with Azapeptide Tocolytics

  摘要：

  The prostaglandin-F2 alpha (PGF2 alpha) receptor (FP) was targeted to develop tocolytic agents for inhibiting preterm labor. Azabicycloalkane and azapeptide mimics 2-10 were synthesized based on the (3S,6S,9S)-indolizidin-2-one amino acid analogue PDC113.824 (1), which was shown to modulate FP by a biased allosteric mechanism, involving both G alpha q- and G alpha 12-mediated signaling pathways, and exhibited significant tocolytic activity delaying preterm labor in a mouse model (Goupil; J. Biol. Chem. 2010, 285,25624-25636), Although changes in azabicycloalkane stereochemistry and ring size caused loss of activity, replacement of the indolizidin-2-one amino acid with azaGly-Pro and azaPhe-Pro gave azapeptides 6 and 8, which reduced PGF2 alpha-induced myometrial contractions, potentiated the effect of PGF2 alpha on G alpha q-mediated ERK1/2 activation, and inhibited FP modulation of cell ruffling, a response dependent on the G alpha 12/RhoA/ROCK signaling pathway. Revealing complementarities of azabicycloalkane and azapeptide mimics, novel probes, and efficient tocolytic agents were made to study allosteric modulation of the FP receptor.

  DOI：

  10.1021/jm200608k
• 作为产物：
  描述：

  在 potassium trimethylsilonate 作用下， 以 乙醚 为溶剂， 反应 0.5h， 生成 (2S,5S,8aR)-2-(tert-Butoxycarbonylamino)-3-oxooctahydroindolizine-5-carboxylic acid 、 (2S,5S,8aS)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxo-2,5,6,7,8,8a-hexahydro-1H-indolizine-5-carboxylic acid
  参考文献：
  名称：

  用于合成对映体纯的α，ω-二氨基二羧酸酯和氮杂双环[XY0]烷烃氨基酸的油化条目。

  摘要：

  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）

  DOI：

  10.1021/jo9814602

文献信息

• Probing Opioid Receptor Interactions with Azacycloalkane Amino Acids. Synthesis of a Potent and Selective ORL1 Antagonist
  作者：Liliane Halab、Jérôme A. J. Becker、Zsuzsanna Darula、Dirk Tourwé、Brigitte L. Kieffer、Frédéric Simonin、William D. Lubell

  DOI：10.1021/jm020078l

  日期：2002.11.1

  between conformation and biological activity of peptide ligands to the opioid receptor-like (ORL1) receptor. Three azabicyclo[x.y.0]alkane amino acids and a 5-tBuPro type VI beta-turn mimic were introduced into peptides 10-13 by solid-phase synthesis on MBHA resin. Biological examination of peptides 10-13 showed two new antagonists (10 and 12) exhibiting increased selectivity for the ORL1 receptor.

  氮杂环烷转向模拟物6-9用于研究肽配体对阿片样受体样（ORL1）受体的构象与生物学活性之间的关系。通过在MBHA树脂上进行固相合成，将三个氮杂双环[xy0]烷烃氨基酸和一个5-tBuPro VI型β转角模拟物引入到肽10-13中。肽10-13的生物学检查显示，两种新的拮抗剂（10和12）对ORL1受体的选择性增加。
• SECONDARY STRUCTURE STABILIZED NMDA RECEPTOR MODULATORS AND USES THEREOF
  申请人：Northwestern University

  公开号：US20160115197A1

  公开（公告）日：2016-04-28

  Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of diseases and disorders such as learning, cognitive activities, and analgesia, particularly in alleviating and/or reducing neuropathic pain.

  本发明揭示了在调节NMDA受体活性方面具有增强效力的化合物。此类化合物可用于治疗学习、认知活动和镇痛等疾病和障碍，特别是在缓解和/或减轻神经病理性疼痛方面。
• US9593145B2
  申请人：——

  公开号：US9593145B2

  公开（公告）日：2017-03-14
• 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）
• Targeting the Prostaglandin F2α Receptor for Preventing Preterm Labor with Azapeptide Tocolytics
  作者：Carine B. Bourguet、Eugénie Goupil、Danaë Tassy、Xin Hou、Eryk Thouin、Felix Polyak、Terence E. Hébert、Audrey Claing、Stéphane A. Laporte、Sylvain Chemtob、William D. Lubell

  DOI：10.1021/jm200608k

  日期：2011.9.8

  The prostaglandin-F2 alpha (PGF2 alpha) receptor (FP) was targeted to develop tocolytic agents for inhibiting preterm labor. Azabicycloalkane and azapeptide mimics 2-10 were synthesized based on the (3S,6S,9S)-indolizidin-2-one amino acid analogue PDC113.824 (1), which was shown to modulate FP by a biased allosteric mechanism, involving both G alpha q- and G alpha 12-mediated signaling pathways, and exhibited significant tocolytic activity delaying preterm labor in a mouse model (Goupil; J. Biol. Chem. 2010, 285,25624-25636), Although changes in azabicycloalkane stereochemistry and ring size caused loss of activity, replacement of the indolizidin-2-one amino acid with azaGly-Pro and azaPhe-Pro gave azapeptides 6 and 8, which reduced PGF2 alpha-induced myometrial contractions, potentiated the effect of PGF2 alpha on G alpha q-mediated ERK1/2 activation, and inhibited FP modulation of cell ruffling, a response dependent on the G alpha 12/RhoA/ROCK signaling pathway. Revealing complementarities of azabicycloalkane and azapeptide mimics, novel probes, and efficient tocolytic agents were made to study allosteric modulation of the FP receptor.