Mechanistic insight into the prebiotic syntheses of pyrimidine ribonucleotide and pyrimidine deoxynucleotide precursors

Abstract

Density functional theory is utilized to elucidate the detailed mechanisms of the reactions between 2-aminooxazole O2/2-aminothiazole S2 and glyceraldehyde 2. According to our calculations, in O2/2 system, aminooxazoline O3 is formed via two steps including CC formation and cyclization. CC formation determines the reaction diastereoselectivity and ribo-aminooxazoline is the most favorable product. Although oxazole-hemiaminal O6 is not detected in the experiment, it is deduced can be formed theoretically. In S2/2 system, aminothiazoline S3 is hard to be generated because of the less nucleophilic ability of S2. The formation of thiazole-hemiaminal S6 is more favorable than S3 formation in kinetics but somewhat unfavorable in thermodynamics. However, the transformation from S6 to thiazole-aminal S7 is favorable both in kinetics and thermodynamics, which provides a driving force for the formation and transformation of S6. Additionally, our calculations indicate that phosphate is very important in assisting proton transfer in all of the transformations.