| Institution: | 1. Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA, 92037 USA;2. Department of Pharmaceutical Sciences, University of California Irvine, 101 Theory, Suite 100, Irvine, CA, 92617 USA;3. Pfizer Medicinal Chemistry, Eastern Point Road, Groton, CT, 06340 USA;4. Pfizer Medicinal Chemistry, 10578 Science Center Drive, San Diego, CA, 92121 USA;5. Automated Synthesis Facility, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA, 92037 USA;6. Department of Pharmaceutical Sciences, University of California Irvine, 101 Theory, Suite 100, Irvine, CA, 92617 USA
Departments of Chemistry & Biomedical Engineering, University of California Irvine, 101 Theory, Suite 100, Irvine, CA, 92617 USA |
| Abstract: | Preparative reactions that occur efficiently under dilute, buffered, aqueous conditions in the presence of biomolecules find application in ligation, peptide synthesis, and polynucleotide synthesis and sequencing. However, the identification of functional groups or reagents that are mutually reactive with one another, but unreactive with biopolymers and water, is challenging. Shown here are cobalt catalysts that react with alkenes under dilute, aqueous, buffered conditions and promote efficient cycloisomerization and formal Friedel–Crafts reactions. The constraining conditions of bioorthogonal chemistry are beneficial for reaction efficiency as superior conversion at low catalyst concentration is obtained and competent rates in dilute conditions are maintained. Efficiency at high dilution in the presence of buffer and nucleobases suggests that these reaction conditions may find broad application. |
