Conformational studies of novel antiretroviral analogs of zidovudine
Conformational properties of three novel zidovudine analogs, namely 3′-azido-3′-deoxy-5′-O-isonicotinoylthymidine (AZT-Iso, 2), (-)-trans-(5S,6S)-5-bromo-6, 5′-epoxy-5,6-dihydro-3′-azido-3′-deoxythymidine (3) and (+)-trans-(5R,6R)-5-bromo-6,5′-epoxy-5,6-dihydro-3′- azido-3′-deoxythymidine (4), have...
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todo:paper_15257770_v22_n1_p45_Baumgartner2023-10-03T16:21:04Z Conformational studies of novel antiretroviral analogs of zidovudine Baumgartner, M.T. Motura, M.I. Contreras, R.H. Pierini, A.B. Briñón, M.C. AM1 calculations Antiretroviral analogs Conformational analysis NMR studies Novel AZT derivatives 3' azido 3' deoxy 5' o isonicotinoylthymidine 5 bromo 6,5' epoxy 5,6 dihydro 3' azido 3' deoxythymidine nucleoside unclassified drug zidovudine zidovudine derivative analytic method article calculation correlation analysis diastereoisomer drug conformation nuclear magnetic resonance nuclear magnetic resonance spectroscopy rotation structure analysis Anti-Retroviral Agents Magnetic Resonance Spectroscopy Molecular Conformation Zidovudine Conformational properties of three novel zidovudine analogs, namely 3′-azido-3′-deoxy-5′-O-isonicotinoylthymidine (AZT-Iso, 2), (-)-trans-(5S,6S)-5-bromo-6, 5′-epoxy-5,6-dihydro-3′-azido-3′-deoxythymidine (3) and (+)-trans-(5R,6R)-5-bromo-6,5′-epoxy-5,6-dihydro-3′- azido-3′-deoxythymidine (4), have been investigated by AM1 calculations and NMR studies, and compared with those of the parent nucleoside (AZT, 1). Based on the results obtained the following correlation may be established, a) AZT and AZT-Iso exhibit a conformational behavior analog to other pyrimidinic nucleosides, displaying a dynamic equilibrium in solution where the two conformers (North and South) undergo a constant transformation. b) Compounds 3 and 4 show a different conformational profile. The estimate of the pseudorotation phase angle reveals the rigid structures of the latter compounds, which do not evidence conformational equilibrium in solution; the azide group being the only group free to rotate. c) Diastereoisomers 3 and 4 exhibit an extra conformational parameter compared with other pyrimidinic nucleosides: the chair or boat conformation in the third ring formed between the sugar and the base. In all cases, a reasonable correlation was obtained between theoretical and NMR spectroscopic data. Fil:Contreras, R.H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_15257770_v22_n1_p45_Baumgartner |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
AM1 calculations Antiretroviral analogs Conformational analysis NMR studies Novel AZT derivatives 3' azido 3' deoxy 5' o isonicotinoylthymidine 5 bromo 6,5' epoxy 5,6 dihydro 3' azido 3' deoxythymidine nucleoside unclassified drug zidovudine zidovudine derivative analytic method article calculation correlation analysis diastereoisomer drug conformation nuclear magnetic resonance nuclear magnetic resonance spectroscopy rotation structure analysis Anti-Retroviral Agents Magnetic Resonance Spectroscopy Molecular Conformation Zidovudine |
| spellingShingle |
AM1 calculations Antiretroviral analogs Conformational analysis NMR studies Novel AZT derivatives 3' azido 3' deoxy 5' o isonicotinoylthymidine 5 bromo 6,5' epoxy 5,6 dihydro 3' azido 3' deoxythymidine nucleoside unclassified drug zidovudine zidovudine derivative analytic method article calculation correlation analysis diastereoisomer drug conformation nuclear magnetic resonance nuclear magnetic resonance spectroscopy rotation structure analysis Anti-Retroviral Agents Magnetic Resonance Spectroscopy Molecular Conformation Zidovudine Baumgartner, M.T. Motura, M.I. Contreras, R.H. Pierini, A.B. Briñón, M.C. Conformational studies of novel antiretroviral analogs of zidovudine |
| topic_facet |
AM1 calculations Antiretroviral analogs Conformational analysis NMR studies Novel AZT derivatives 3' azido 3' deoxy 5' o isonicotinoylthymidine 5 bromo 6,5' epoxy 5,6 dihydro 3' azido 3' deoxythymidine nucleoside unclassified drug zidovudine zidovudine derivative analytic method article calculation correlation analysis diastereoisomer drug conformation nuclear magnetic resonance nuclear magnetic resonance spectroscopy rotation structure analysis Anti-Retroviral Agents Magnetic Resonance Spectroscopy Molecular Conformation Zidovudine |
| description |
Conformational properties of three novel zidovudine analogs, namely 3′-azido-3′-deoxy-5′-O-isonicotinoylthymidine (AZT-Iso, 2), (-)-trans-(5S,6S)-5-bromo-6, 5′-epoxy-5,6-dihydro-3′-azido-3′-deoxythymidine (3) and (+)-trans-(5R,6R)-5-bromo-6,5′-epoxy-5,6-dihydro-3′- azido-3′-deoxythymidine (4), have been investigated by AM1 calculations and NMR studies, and compared with those of the parent nucleoside (AZT, 1). Based on the results obtained the following correlation may be established, a) AZT and AZT-Iso exhibit a conformational behavior analog to other pyrimidinic nucleosides, displaying a dynamic equilibrium in solution where the two conformers (North and South) undergo a constant transformation. b) Compounds 3 and 4 show a different conformational profile. The estimate of the pseudorotation phase angle reveals the rigid structures of the latter compounds, which do not evidence conformational equilibrium in solution; the azide group being the only group free to rotate. c) Diastereoisomers 3 and 4 exhibit an extra conformational parameter compared with other pyrimidinic nucleosides: the chair or boat conformation in the third ring formed between the sugar and the base. In all cases, a reasonable correlation was obtained between theoretical and NMR spectroscopic data. |
| format |
JOUR |
| author |
Baumgartner, M.T. Motura, M.I. Contreras, R.H. Pierini, A.B. Briñón, M.C. |
| author_facet |
Baumgartner, M.T. Motura, M.I. Contreras, R.H. Pierini, A.B. Briñón, M.C. |
| author_sort |
Baumgartner, M.T. |
| title |
Conformational studies of novel antiretroviral analogs of zidovudine |
| title_short |
Conformational studies of novel antiretroviral analogs of zidovudine |
| title_full |
Conformational studies of novel antiretroviral analogs of zidovudine |
| title_fullStr |
Conformational studies of novel antiretroviral analogs of zidovudine |
| title_full_unstemmed |
Conformational studies of novel antiretroviral analogs of zidovudine |
| title_sort |
conformational studies of novel antiretroviral analogs of zidovudine |
| url |
http://hdl.handle.net/20.500.12110/paper_15257770_v22_n1_p45_Baumgartner |
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