Synthesis, structural, conformational and DFT studies of N-3 and O-4 alkylated regioisomers of 5-(hydroxypropyl)pyrimidine
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2015
Authors
Salihovic, MirsadaOsmanović, Amar
Špirtović-Halilović, Selma
Roca, Sunčica
Meščić, Andrijana
Vujisić, Ljubodrag V.
Trifunović, Snežana S.
Završnik, Davorka
Sofić, Emin
Article (Published version)
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Because of the great pharmacological potential of the pyrimidine motif, novel C-5 substituted N-3 acyclic and O-4 acyclic pyrimidine derivatives were prepared as an interesting class of compounds for biological evaluation. Introduction of the 2,3-dihydroxypropyl (DHP) and penciclovir (PCV)-like side chains to 2-methoxypyrimidin-4-one (2) afforded a mixture of N- and O-acyclic pyrimidine nucleosides in the ratio of 54: 29 (3:4) and 57:21 (5:6) with N-3 isomer being dominant. Distinction between N- and O-alkylated pyrimidine moiety was deduced from extensive experimental FT-IR, HPLC-MS and 1D (H-1, C-13) and 2D (COSY, HMQC and HMBC) NMR analyses. The N-, O-regioisomers were also examined by computational method at density functional theory (DFT) RB3LYP/6-31G(d), 6-31G** and 6-31+G* levels. DFT global chemical reactivity descriptors (total energy, chemical hardness, electronic chemical potential and electrophilicity) were calculated for the isomers and used to predict and describe their r...elative stability and reactivity. The chemical reactivity indices were related to the C-2-N-3-C-4 bond angle. Theoretical predictions can be used to compare chemical reactivity and stability with future biological evaluation and behaviour of these compounds.
Keywords:
N-, O-acyclic pyrimidine nucleosides / 2,3-Dihydroxypropyl (DHP) / 4-Hydroxy-(3-hydroxymethyl)butyl (PCV) / NMR / FT-IR / DFT calculationSource:
Journal of Molecular Structure, 2015, 1091, 170-176Publisher:
- Elsevier Science Bv, Amsterdam
Funding / projects:
- Federal Ministry of Education and Science project (the Federation of Bosnia and Herzegovina) [05-39-4362-1/13, 0101-39-145/13]
Note:
- Peer-reviewed manuscript: http://cherry.chem.bg.ac.rs/handle/123456789/3448
DOI: 10.1016/j.molstruc.2015.02.078
ISSN: 0022-2860
WoS: 000353610600025
Scopus: 2-s2.0-84925206316
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Institution/Community
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Salihovic, Mirsada AU - Osmanović, Amar AU - Špirtović-Halilović, Selma AU - Roca, Sunčica AU - Meščić, Andrijana AU - Vujisić, Ljubodrag V. AU - Trifunović, Snežana S. AU - Završnik, Davorka AU - Sofić, Emin PY - 2015 UR - https://cherry.chem.bg.ac.rs/handle/123456789/1696 AB - Because of the great pharmacological potential of the pyrimidine motif, novel C-5 substituted N-3 acyclic and O-4 acyclic pyrimidine derivatives were prepared as an interesting class of compounds for biological evaluation. Introduction of the 2,3-dihydroxypropyl (DHP) and penciclovir (PCV)-like side chains to 2-methoxypyrimidin-4-one (2) afforded a mixture of N- and O-acyclic pyrimidine nucleosides in the ratio of 54: 29 (3:4) and 57:21 (5:6) with N-3 isomer being dominant. Distinction between N- and O-alkylated pyrimidine moiety was deduced from extensive experimental FT-IR, HPLC-MS and 1D (H-1, C-13) and 2D (COSY, HMQC and HMBC) NMR analyses. The N-, O-regioisomers were also examined by computational method at density functional theory (DFT) RB3LYP/6-31G(d), 6-31G** and 6-31+G* levels. DFT global chemical reactivity descriptors (total energy, chemical hardness, electronic chemical potential and electrophilicity) were calculated for the isomers and used to predict and describe their relative stability and reactivity. The chemical reactivity indices were related to the C-2-N-3-C-4 bond angle. Theoretical predictions can be used to compare chemical reactivity and stability with future biological evaluation and behaviour of these compounds. PB - Elsevier Science Bv, Amsterdam T2 - Journal of Molecular Structure T1 - Synthesis, structural, conformational and DFT studies of N-3 and O-4 alkylated regioisomers of 5-(hydroxypropyl)pyrimidine VL - 1091 SP - 170 EP - 176 DO - 10.1016/j.molstruc.2015.02.078 ER -
@article{ author = "Salihovic, Mirsada and Osmanović, Amar and Špirtović-Halilović, Selma and Roca, Sunčica and Meščić, Andrijana and Vujisić, Ljubodrag V. and Trifunović, Snežana S. and Završnik, Davorka and Sofić, Emin", year = "2015", abstract = "Because of the great pharmacological potential of the pyrimidine motif, novel C-5 substituted N-3 acyclic and O-4 acyclic pyrimidine derivatives were prepared as an interesting class of compounds for biological evaluation. Introduction of the 2,3-dihydroxypropyl (DHP) and penciclovir (PCV)-like side chains to 2-methoxypyrimidin-4-one (2) afforded a mixture of N- and O-acyclic pyrimidine nucleosides in the ratio of 54: 29 (3:4) and 57:21 (5:6) with N-3 isomer being dominant. Distinction between N- and O-alkylated pyrimidine moiety was deduced from extensive experimental FT-IR, HPLC-MS and 1D (H-1, C-13) and 2D (COSY, HMQC and HMBC) NMR analyses. The N-, O-regioisomers were also examined by computational method at density functional theory (DFT) RB3LYP/6-31G(d), 6-31G** and 6-31+G* levels. DFT global chemical reactivity descriptors (total energy, chemical hardness, electronic chemical potential and electrophilicity) were calculated for the isomers and used to predict and describe their relative stability and reactivity. The chemical reactivity indices were related to the C-2-N-3-C-4 bond angle. Theoretical predictions can be used to compare chemical reactivity and stability with future biological evaluation and behaviour of these compounds.", publisher = "Elsevier Science Bv, Amsterdam", journal = "Journal of Molecular Structure", title = "Synthesis, structural, conformational and DFT studies of N-3 and O-4 alkylated regioisomers of 5-(hydroxypropyl)pyrimidine", volume = "1091", pages = "170-176", doi = "10.1016/j.molstruc.2015.02.078" }
Salihovic, M., Osmanović, A., Špirtović-Halilović, S., Roca, S., Meščić, A., Vujisić, L. V., Trifunović, S. S., Završnik, D.,& Sofić, E.. (2015). Synthesis, structural, conformational and DFT studies of N-3 and O-4 alkylated regioisomers of 5-(hydroxypropyl)pyrimidine. in Journal of Molecular Structure Elsevier Science Bv, Amsterdam., 1091, 170-176. https://doi.org/10.1016/j.molstruc.2015.02.078
Salihovic M, Osmanović A, Špirtović-Halilović S, Roca S, Meščić A, Vujisić LV, Trifunović SS, Završnik D, Sofić E. Synthesis, structural, conformational and DFT studies of N-3 and O-4 alkylated regioisomers of 5-(hydroxypropyl)pyrimidine. in Journal of Molecular Structure. 2015;1091:170-176. doi:10.1016/j.molstruc.2015.02.078 .
Salihovic, Mirsada, Osmanović, Amar, Špirtović-Halilović, Selma, Roca, Sunčica, Meščić, Andrijana, Vujisić, Ljubodrag V., Trifunović, Snežana S., Završnik, Davorka, Sofić, Emin, "Synthesis, structural, conformational and DFT studies of N-3 and O-4 alkylated regioisomers of 5-(hydroxypropyl)pyrimidine" in Journal of Molecular Structure, 1091 (2015):170-176, https://doi.org/10.1016/j.molstruc.2015.02.078 . .