Reaction discovery enabled by DNA-templated synthesis and in vitro selection

Area of Science:

• Organic Chemistry
• Chemical Biology
• Synthetic Chemistry

Background:

• Traditional reaction discovery methods focus on single transformations, potentially missing unexplored reactivity.
• Current approaches often involve laborious screening of substrates and conditions.

Purpose of the Study:

• To develop a novel, high-throughput method for discovering new chemical reactions.
• To explore a broader range of substrate combinations and reaction conditions simultaneously.

Main Methods:

• Utilized DNA-templated organic synthesis to control substrate proximity and effective molarity via Watson-Crick base pairing.
• Employed in vitro selection, PCR amplification, and DNA microarray analysis to identify successful bond-forming reactions.
• Screened multiple substrate combinations in a single solution.

Main Results:

• Discovered an efficient and mild carbon-carbon bond-forming reaction.
• The new reaction synthesizes enones from alkynes and alkenes using an inorganic palladium catalyst.
• Demonstrated the simultaneous evaluation of numerous substrate combinations.

Conclusions:

• The DNA-templated in vitro selection approach enables efficient and simultaneous discovery of chemical reactions.
• This versatile method expands the scope of explored chemical reactivity.
• Future applications may uncover diverse new reactions compatible with DNA-based systems.