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dc.contributor.authorRoggen, Heidi
dc.contributor.authorBohlin, Lars
dc.contributor.authorBurman, Robert
dc.contributor.authorCharnock, Colin
dc.contributor.authorFelth, Jenny
dc.contributor.authorGorbitz, Carl Henrik
dc.contributor.authorLarsson, Rolf
dc.contributor.authorTamm, Toomas
dc.contributor.authorGundersen, Lise-Lotte
dc.date.accessioned2011-02-21T11:48:15Z
dc.date.available2011-02-21T11:48:15Z
dc.date.issued2011-01-25
dc.identifier.citationRoggen, H., Bohlin, L., Burman, R., Charnock, C., Felth, J., Gorbitz, C.H. ... Gundersen, L-L. (2010). 2-Substituted agelasine analogs : Synthesis and biological activity, and structure and reactivity of synthetic intermediates. Pure and Applied Chemistry, 83 (3), 645-653en_US
dc.identifier.issnPrint: 0033-4545
dc.identifier.issnOnline: 1365-3075
dc.identifier.urihttp://hdl.handle.net/10642/591
dc.description.abstract2-Substituted N-methoxy-9-methyl-9H-purin-6-amines were synthesized either from their corresponding 6-chloro-9-methyl-9H-purines or 2-chloro-N-methoxy-9-methyl- 9H-purin-6-amine. Great diversity in the amino/imino tautomeric ratios was observed and calculated based on 1H NMR. The tautomers were identified by 1D and 2D 1H, 13C, and 15N NMR techniques, and showed significant variation both in 13C and 15N shift values. Comparison of the tautomeric ratios with Hammett F values revealed that as the field/inductive withdrawing abilities of the 2-substituent increased, the ratio of amino:imino tautomers was shifted toward the amino tautomer. Computational chemistry exposed the significance of hydrogen bonding between solvent and the compound in question to reach accurate predictions for tautomeric ratios. B3LYP/def2-TZVP density functional theory (DFT) calculations resulted in quantitatively more accurate predictions than when employing the less expensive BP86 functional. N-7-Alkylation of the 2-substituted N-methoxy-9-methyl-9H-purin-6- amines showed that when the field/inductive withdrawing ability of the 2-substituent reached a certain point the reactivity drastically dropped. This correlated with the atomic charges on N-7 calculated using a natural bond orbital (NBO) analysis. Biological screening of the final 2-substituted agelasine analogs indicated that the introduction of a methyl group in the 2-position is advantageous for antimycobacterial and antiprotozoal activity, and that an amino function may improve activity against several cancer cell lines.en_US
dc.language.isoengen_US
dc.publisherInternational Union of Pure and Applied Chemistryen_US
dc.relation.ispartofseriesPure and Applied Chemistry;83 (3)
dc.subjectAgelasineen_US
dc.subjectBiological activityen_US
dc.subjectDensity functional theoryen_US
dc.subjectPurineen_US
dc.subjectTautomerismen_US
dc.subjectX-ray crystallographyen_US
dc.title2-Substituted agelasine analogs : synthesis and biological activity, and structure and reactivity of synthetic intermediatesen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.identifier.doihttp://dx.doi.org/10.1351/PAC-CON-10-09-25


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