Prebiotically plausible chemoselective pantetheine synthesis in water

Area of Science:

• Origin of Life studies
• Prebiotic Chemistry
• Biochemistry

Background:

• Coenzyme A (CoA) is vital for all life.
• Pantetheine, CoA's functional subunit, is crucial for origin-of-life scenarios.
• Previous attempts to synthesize pantetheine prebiotically were unsuccessful, suggesting simpler molecules preceded it.

Purpose of the Study:

• To investigate the prebiotic synthesis of pantetheine.
• To determine if pantetheine could have emerged on early Earth.
• To challenge the hypothesis that simpler thiols preceded pantetheine.

Main Methods:

• Utilized chemoselective multicomponent reactions in dilute water.
• Employed aldol, iminolactone, and aminonitrile reactions.
• Achieved spontaneous differentiation of key pantetheine moieties.

Main Results:

• Reported high-yielding and selective prebiotic syntheses of pantetheine.
• Demonstrated the formation of pantoic acid and proteinogenic amino acids.
• Successfully synthesized the dihydroxyl, gem-dimethyl, and β-alanine-amide components of pantetheine.

Conclusions:

• Pantetheine can be synthesized selectively under plausible prebiotic conditions.
• The findings support a role for canonical pantetheine at the origin of life.
• This research provides a pathway for the emergence of essential biomolecules.