A Plausible Prebiotic One‐Pot Synthesis of Orotate and Pyruvate Suggestive of Common Protometabolic Pathways. Issue 11 (27th January 2022)

• Record Type: Journal Article
• Authors: Clay, Alyssa P.; Cooke, Rachel E.; Kumar, Ravi; Yadav, Mahipal; Krishnamurthy, Ramanarayanan; Springsteen, Greg
• Is Part Of: Angewandte Chemie international edition. Volume 61:Issue 11(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-01-27
• Subjects: Pyrimidine Synthesis -- Pyruvate Synthesis -- Prebiotic Chemistry; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202112572
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: A reaction between two prebiotically plausible building blocks, hydantoin and glyoxylate, generates both the nucleobase orotate, a precursor of biological pyrimidines, and pyruvate, a core metabolite in the citric acid cycle and amino acid biosynthesis. The reaction proceeds in water to provide significant yields of the two widely divergent chemical motifs. Additionally, the reaction of thiohydantoin and glyoxylate produces thioorotate in high yield under neutral aqueous conditions. The use of an open‐chain thiohydantoin derivative also enables the potential pre‐positioning of a nucleosidic bond prior to the synthesis of an orotate nucleoside. The observation that diverse building blocks of modern metabolism can be produced in a single reaction pot, from common reactants under mild conditions, supports the plausibility of orthogonal chemistries operating at the origins of chemical evolution. Abstract : A prebiotic synthesis of the nucleobase orotate, and the citric acid cycle intermediate pyruvate, proceeds in a single pot from two small glycine derivatives, hydantoin and glyoxylate, under mild aqueous conditions. These findings support a co‐evolution of pathways to core protometabolites and nucleic acid building blocks in a common environment. Additionally, open‐chain thiohydantoin derivatives enable a synthesis of thioorotate nucleosides.