Control and design of mutual orthogonality in bioorthogonal cycloadditions
Yong Liang1, Joel L Mackey, Steven A Lopez
1Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
Abstract:
The azide-dibenzocyclooctyne and trans-cyclooctene-tetrazine cycloadditions are both bioorthogonal and mutually orthogonal: trans-cyclooctene derivatives greatly prefer to react with tetrazines rather than azides, while dibenzocyclooctyne derivatives react with azides but not with tetrazines under physiological conditions. DFT calculations used to identify the origins of this extraordinary selectivity are reported, and design principles to guide discovery of new orthogonal cycloadditions are proposed. Two new bioorthogonal reagents, methylcyclopropene and 3,3,6,6-tetramethylthiacycloheptyne, are predicted to be mutually orthogonal in azide and tetrazine cycloadditions.
More Related Videos
09:06Efficient and Site-specific Antibody Labeling by Strain-promoted Azide-alkyne Cycloaddition
Published on: December 23, 2016
14:02Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells
Published on: April 9, 2018
Related Concept Videos
Cycloaddition Reactions: MO Requirements for Thermal Activation
Cycloaddition Reactions: Overview
Cycloaddition Reactions: MO Requirements for Photochemical Activation
Regioselectivity and Stereochemistry of Hydroboration
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
