Formation of Conjugate Adducts in the Reactions of Malonaldehyde-Acetaldehyde and Malonaldehyde-Formaldehyde with Guanosine

摘要

The reactions of guanosine with malonaldehyde in buffered aqueous solutions in the presence of acetaldehyde or formaldehyde were studied.The reaction mixtures were analyzed by RP-HPLC.Two adducts were formed in the reaction of malonaldehyde and acetaldehyde and one in the reaction of malonaldehyde and formaldehyde.The products were isolated and purified by preparative C-18 chromatography and structurally characterized by UV absorbance,~1H NMR,and ~(13)C NMR spectroscopy and mass spectrometry.The adducts formed in the reaction of malonaldehyde and acetaldehyde were identified as 7-(2,2-diforniyl-l-methylethyl)-3-(beta-D-ribofuranosyl)pyrimido[1,-a]-purin-10(3H)-one (M_2AA-Guo I) and 2-(3,5-diformyl-4-methyl-l,4-dihydro-l-pyridyl)-9-(beta-D-ribofuranosyl)-purin-6(9H)-one (M_2AA-Guo II).In the reaction of malonaldehyde and formaldehyde,the major product was identified as 7-formyl-3-(beta-D-ribofuranosyl)pyrimido[l,2-a]purin-10(8H)-one (M_1FA-Guo).The highest yields of M_2AA-Guo I and M_2AA-Guo II,7 and 2 mol %,respectively,were obtained in the reaction performed at pH 7.4 and 37 deg C for 6 days,while MiFA-Guo was produced at a yield of 0.3 mol % after 3 days of reaction at pH 7.4 and 37 deg C.The products are formed by reactions of malonaldehyde- acetaldehyde and malonaldehyde-formaldehyde condensation products with guanosine and are analogous to the previously identified condensation products formed with adenosine,cytidine,and proteins.