Formation of a β-Pyrimidine Nucleoside by a Free Pyrimidine Base and Ribose in a Plausible Prebiotic Reaction

• Published in: Journal of the American Chemical Society Vol. 129; no. 31; pp. 9556 - 9557
• Main Authors: Bean, Heather D, Sheng, Yinghong, Collins, James P, Anet, Frank A. L, Leszczynski, Jerzy, Hud, Nicholas V
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 08.08.2007; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Chromatography, High Pressure Liquid; Glycosylation; Molecular Structure; Physical Sciences; Pyrimidine Nucleosides - chemistry; Ribose - chemistry; Science & Technology; RECOGNITION ELEMENTS; OLIGODIPEPTIDES; TRANSITION-STATE; LANDSCAPE; PRIMORDIAL INFORMATIONAL OLIGOMERS
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja072781a

The problem of β-nucleoside formation under prebiotic conditions represents one of the most significant challenges to the RNA world hypothesis and to many of its proposed precursors. The possibility exists that alternative bases may have come before the contemporary bases (i.e., A, G, C, and U), including bases that more readily form nucleosides. In a search for pyrimidine bases that are able to form nucleosides in plausible prebiotic reactions, it was discovered that the drying and heating of 2-pyrimidinone with ribose produces a β-furanosyl ribonucleoside in approximately 12% yield. At least two other chemical isomers of zebularine are also produced in the condensation reaction. This work represents the first successful synthesis of a pyrimidine nucleoside from a free base and a nonactivated sugar in a plausible prebiotic reaction. A comparison of 2-pyrimidinone with the purine bases that have also been demonstrated to form nucleosides in plausible prebiotic reactions provides insights regarding what chemical features of the bases facilitate glycoside formation in drying-heating reactions.