Sugar-Driven Prebiotic Synthesis of 3,5(6)-Dimethylpyrazin-2-one: A Possible Nucleobase of a Primitive Replication Process

• Published in: Origins of life and evolution of biospheres Vol. 38; no. 4; pp. 279 - 292
• Main Author: Weber, Arthur L.
• Format: Journal Article
• Language: English; Dutch
• Published: Dordrecht Springer Netherlands 01.08.2008; Springer Nature B.V
• Subjects: Alanine; Alanine - chemistry; Amides; Amines - chemistry; Ammonia; Ammonium Chloride - chemistry; Astronomy; Astrophysics and Astroparticles; Base Composition; Biochemistry; Biomedical and Life Sciences; Biosynthesis; Carbohydrates - chemistry; Chemical synthesis; Chemistry - methods; Earth Sciences; Enzymes; Evolution; Evolution, Chemical; Glyceraldehyde; Glyceraldehyde - chemistry; Hydrogen-Ion Concentration; Isomers; Life Sciences; Models, Chemical; Molecular biology; Monomers; Observations and Techniques; Origin of Life; Prebiotic Chemistry; Prebiotics; Pyrazines - chemistry; Pyrazines - metabolism; Spectrophotometry, Ultraviolet; Sugar; Time Factors; Transcription; Sugar–amine reaction; Pyrazinone synthesis; Prebiotic chemistry; Origin of life; Nucleobase synthesis; Glyceraldehyde; Sugar chemistry; Template replication; Alanine amide
• ISSN: 0169-6149; 1573-0875
• DOI: 10.1007/s11084-008-9141-6

Reaction of glyceraldehyde with alanine amide (or ammonia) under anaerobic aqueous conditions yielded 3,5(6)-dimethylpyrazin-2-one that is considered a possible complementary residue of a primitive replicating molecule that preceded RNA. Synthesis of the dimethylpyrazin-2-one isomers under mild aqueous conditions (65°C, pH 5.5) from 100 mM glyceraldehyde and alanine amide (or ammonia) was complete in about 5 days. This synthesis using 25 mM glyceraldehyde and alanine amide gave a total pyrazinone yield of 9.3% consisting of 42% of the 3,5-dimethylprazin-2-one isomer and 58% of the 3,6-dimethylpyrazin-2-one isomer. The related synthesis of the dimethylpyrazin-2-one isomers from glyceraldehyde and ammonia was about 200-fold less efficient than the alanine amide reaction. This synthetic process is considered a reasonable model of origin-of-life chemistry because it uses plausible prebiotic substrates, and resembles modern biosynthesis by employing the energized carbon groups of sugars to drive the synthesis of small organic molecules. Possible sugar-driven pathways for the prebiotic synthesis of polymerizable 2-pyrazinone monomers are discussed.