Symmetry-based design for the chemoenzymatic synthesis of oseltamivir (Tamiflu) from ethyl benzoate.
A short chemoenzymatic formal synthesis of oseltamivir from ethyl benzoate has been achieved. The key steps involve a toluene dioxygenase-mediated dihydroxylation, hetero-Diels-Alder cycloaddition, and generation of C4 acetamido functionality. The formal synthesis of oseltamivir is achieved in ten steps and incorporates a unique translocation of the olefin with concomitant elimination of the C2 hydroxy group (see scheme).
Sullivan
Bradford
B
Department of Chemistry and Centre for Biotechnology, Brock University, 500 Glenridge Avenue, St. Catharines, Ontario, L2S 3A1, Canada.
Carrera
Ignacio
I
Drouin
Melissa
M
Hudlicky
Tomas
T
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000378:metabolism; D001565:Benzoates / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism; D053139:Oseltamivir / Q000138:chemical synthesis* / Q000378:metabolism
D000998:Antiviral Agents; D001565:Benzoates; D004791:Enzyme Inhibitors; D053139:Oseltamivir