Synthesis of Orthogonally Protected (+/-)-3-Amino-4-anilidopiperidines and (+/-)-3-N-Carbomethoxyfentanyl
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2017
Authors
Jevtić, Ivana I.Došen-Mićović, Ljiljana
Ivanović, Evica R.
Todorović, Nina
Ivanović, Milovan
Article (Published version)
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The synthesis of orthogonally protected cis- and trans-3-amino-4-anilidopiperidine derivatives has been accomplished in six steps, starting from readily accessible 4-piperidone derivatives. The last three steps, i.e., N-acylation, Hofmann rearrangement, and carbamate cleavage, involved separated (+/-)-cis and (+/-)-trans intermediates. Complete retention of configuration was observed at position 3 of the piperidine ring. Specifically protected positions 1 and 3 at the piperidine scaffold allow for selective deprotection and introduction of diverse substituents at the respective nitrogen sites. The orthogonally protected anilidopiperidines open avenues to potentially pharmacologically active compounds, including opioids and various bivalent ligands for G protein-coupled receptors. In addition, a prototype of a novel class of fentanyl derivatives, possessing a 3-amino group, was synthesized by using the same approach.
Keywords:
heterocycles / rearrangement / acylation / protecting groups / diastereoselectivitySource:
Synthesis, Stuttgart, 2017, 49, 14, 3126-3136Publisher:
- Georg Thieme Verlag Kg, Stuttgart
Funding / projects:
- Structure-activity relationship of newly synthesized biological active compound (RS-MESTD-Basic Research (BR or ON)-172032)
Note:
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3249
DOI: 10.1055/s-0036-1588985
ISSN: 0039-7881
WoS: 000406066800009
Scopus: 2-s2.0-85017147328
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Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Jevtić, Ivana I. AU - Došen-Mićović, Ljiljana AU - Ivanović, Evica R. AU - Todorović, Nina AU - Ivanović, Milovan PY - 2017 UR - https://cherry.chem.bg.ac.rs/handle/123456789/2492 AB - The synthesis of orthogonally protected cis- and trans-3-amino-4-anilidopiperidine derivatives has been accomplished in six steps, starting from readily accessible 4-piperidone derivatives. The last three steps, i.e., N-acylation, Hofmann rearrangement, and carbamate cleavage, involved separated (+/-)-cis and (+/-)-trans intermediates. Complete retention of configuration was observed at position 3 of the piperidine ring. Specifically protected positions 1 and 3 at the piperidine scaffold allow for selective deprotection and introduction of diverse substituents at the respective nitrogen sites. The orthogonally protected anilidopiperidines open avenues to potentially pharmacologically active compounds, including opioids and various bivalent ligands for G protein-coupled receptors. In addition, a prototype of a novel class of fentanyl derivatives, possessing a 3-amino group, was synthesized by using the same approach. PB - Georg Thieme Verlag Kg, Stuttgart T2 - Synthesis, Stuttgart T1 - Synthesis of Orthogonally Protected (+/-)-3-Amino-4-anilidopiperidines and (+/-)-3-N-Carbomethoxyfentanyl VL - 49 IS - 14 SP - 3126 EP - 3136 DO - 10.1055/s-0036-1588985 ER -
@article{ author = "Jevtić, Ivana I. and Došen-Mićović, Ljiljana and Ivanović, Evica R. and Todorović, Nina and Ivanović, Milovan", year = "2017", abstract = "The synthesis of orthogonally protected cis- and trans-3-amino-4-anilidopiperidine derivatives has been accomplished in six steps, starting from readily accessible 4-piperidone derivatives. The last three steps, i.e., N-acylation, Hofmann rearrangement, and carbamate cleavage, involved separated (+/-)-cis and (+/-)-trans intermediates. Complete retention of configuration was observed at position 3 of the piperidine ring. Specifically protected positions 1 and 3 at the piperidine scaffold allow for selective deprotection and introduction of diverse substituents at the respective nitrogen sites. The orthogonally protected anilidopiperidines open avenues to potentially pharmacologically active compounds, including opioids and various bivalent ligands for G protein-coupled receptors. In addition, a prototype of a novel class of fentanyl derivatives, possessing a 3-amino group, was synthesized by using the same approach.", publisher = "Georg Thieme Verlag Kg, Stuttgart", journal = "Synthesis, Stuttgart", title = "Synthesis of Orthogonally Protected (+/-)-3-Amino-4-anilidopiperidines and (+/-)-3-N-Carbomethoxyfentanyl", volume = "49", number = "14", pages = "3126-3136", doi = "10.1055/s-0036-1588985" }
Jevtić, I. I., Došen-Mićović, L., Ivanović, E. R., Todorović, N.,& Ivanović, M.. (2017). Synthesis of Orthogonally Protected (+/-)-3-Amino-4-anilidopiperidines and (+/-)-3-N-Carbomethoxyfentanyl. in Synthesis, Stuttgart Georg Thieme Verlag Kg, Stuttgart., 49(14), 3126-3136. https://doi.org/10.1055/s-0036-1588985
Jevtić II, Došen-Mićović L, Ivanović ER, Todorović N, Ivanović M. Synthesis of Orthogonally Protected (+/-)-3-Amino-4-anilidopiperidines and (+/-)-3-N-Carbomethoxyfentanyl. in Synthesis, Stuttgart. 2017;49(14):3126-3136. doi:10.1055/s-0036-1588985 .
Jevtić, Ivana I., Došen-Mićović, Ljiljana, Ivanović, Evica R., Todorović, Nina, Ivanović, Milovan, "Synthesis of Orthogonally Protected (+/-)-3-Amino-4-anilidopiperidines and (+/-)-3-N-Carbomethoxyfentanyl" in Synthesis, Stuttgart, 49, no. 14 (2017):3126-3136, https://doi.org/10.1055/s-0036-1588985 . .