Synthesis of Orthogonally Protected (+/-)-3-Amino-4-anilidopiperidines and (+/-)-3-N-Carbomethoxyfentanyl
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2017
Authors
Jevtić, Ivana I.Došen-Mićović, Ljiljana I.
Ivanović, Evica
Todorović, Nina M.
Ivanović, Milovan D.
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)
DOI: 10.1055/s-0036-1588985
ISSN: 0039-7881
WoS: 000406066800009
Scopus: 2-s2.0-85017147328
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Poljoprivredni fakultetTY - JOUR AU - Jevtić, Ivana I. AU - Došen-Mićović, Ljiljana I. AU - Ivanović, Evica AU - Todorović, Nina M. AU - Ivanović, Milovan D. PY - 2017 UR - http://aspace.agrif.bg.ac.rs/handle/123456789/4468 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 EP - 3136 IS - 14 SP - 3126 VL - 49 DO - 10.1055/s-0036-1588985 ER -
@article{ author = "Jevtić, Ivana I. and Došen-Mićović, Ljiljana I. and Ivanović, Evica and Todorović, Nina M. and Ivanović, Milovan D.", 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", pages = "3136-3126", number = "14", volume = "49", doi = "10.1055/s-0036-1588985" }
Jevtić, I. I., Došen-Mićović, L. I., Ivanović, E., Todorović, N. M.,& Ivanović, M. D.. (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 LI, Ivanović E, Todorović NM, Ivanović MD. 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 I., Ivanović, Evica, Todorović, Nina M., Ivanović, Milovan D., "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 . .