Enzymatic construction of highly strained carbocycles
Kai Chen1, Xiongyi Huang1, S B Jennifer Kan1
1Division of Chemistry and Chemical Engineering 210-41, California Institute of Technology, Pasadena, CA 91125, USA.
Science (New York, N.Y.)
|April 7, 2018
Summary
Researchers engineered hemeproteins to create chiral bicyclobutanes, highly strained molecules, using successive carbene addition. This enzymatic approach offers an efficient and selective method for synthesizing valuable strained carbocycles.
Area of Science:
- Organic Chemistry
- Biocatalysis
- Protein Engineering
Background:
- Small carbocycles are rigid, high-energy molecules with broad applications but are challenging to synthesize.
- Ring strain in carbocycles contributes to their unique properties and reactivity.
Purpose of the Study:
- To engineer hemeproteins capable of catalyzing the formation of chiral bicyclobutanes.
- To develop an efficient and selective biocatalytic route for synthesizing strained carbocycles.
Main Methods:
- Engineering hemeproteins to catalyze successive carbene addition reactions.
- Identification of enzymes producing cyclopropenes as intermediates.
- Directed evolution for protein optimization.
Main Results:
- Successfully engineered hemeproteins catalyze the formation of chiral bicyclobutanes from unsaturated precursors.
- Identified enzymes that produce cyclopropenes, key intermediates in bicyclobutane synthesis.
- Demonstrated high efficiency, selectivity, and substrate diversity for the engineered enzymes.
- Biocatalytic process is scalable for preparative synthesis.
Conclusions:
- Genetically encoded hemeproteins provide an effective route to chiral strained carbocycles.
- Engineered enzymes offer a sustainable and efficient alternative to traditional chemical synthesis methods.
- The synthesized strained carbocycles can be further derivatized for diverse applications.
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