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).
Department of Chemistry and Centre for Biotechnology, Brock University, 500 Glenridge Avenue, St. Catharines, Ontario, L2S 3A1, Canada.
Bradford
B
Sullivan
Ignacio
I
Carrera
Melissa
M
Drouin
Tomas
T
Hudlicky
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