Synthesis and conformational analysis of carbasugar bioisosteres of alpha-L-iduronic acid and its methyl glycoside
2010 (English)In: Carbohydrate Research, ISSN 0008-6215, E-ISSN 1873-426X, Vol. 345, no 8, 984-993 p.Article in journal (Refereed) Published
The synthesis of two novel carbasugar analogues of α-l-iduronic acid is described in which the ring-oxygen is replaced by a methylene group. In analogy with the conformational equilibrium described for α-l-IdopA, the conformation of the carbasugars was investigated by 1H and 13C NMR spectroscopy. Hadamard transform NMR experiments were utilised for rapid acquisition of 1H,13C-HSQC spectra and efficient measurements of heteronuclear long-range coupling constants. Analysis of 1H NMR chemical shifts and JH,H coupling constants extracted by a total-lineshape fitting procedure in conjunction with JH,C coupling constants obtained by three different 2D NMR experiments, viz., 1H,13C-HSQC-HECADE, J-HMBC and IPAP-HSQC-TOCSY-HT, as well as effective proton–proton distances from 1D 1H,1H T-ROE and NOE experiments showed that the conformational equilibrium 4C12S5a1C4 is shifted towards 4C1 as the predominant or exclusive conformation. These carbasugar bioisosteres of α-l-iduronic acid do not as monomers show the inherent flexibility that is anticipated to be necessary for biological activity.
Place, publisher, year, edition, pages
2010. Vol. 345, no 8, 984-993 p.
Heparin, Conformational equilibrium, NMR, Molecular modelling
Research subject Organic Chemistry
IdentifiersURN: urn:nbn:se:su:diva-59758DOI: 10.1016/j.carres.2010.03.002ISI: 000278747700001OAI: oai:DiVA.org:su-59758DiVA: diva2:430758