Chemoenzymatic synthesis of rivastigmine based on lipase-catalyzed processes.
A straightforward chemoenzymatic synthesis of enantiomerically pure rivastigmine has been efficiently carried out under mild reaction conditions, with Candida antarctica lipase B responsible for the stereoselective acetylation of the corresponding (R)-alcohol or amine. An exhaustive enzymatic study has been developed exploring the possibilities of carry out enzyme recycling, scaling up the enzymatic process and development of a dynamic kinetic resolution procedure for the production of adequate enantiomerically pure precursors of rivastigmine. Total chemoenzymatic synthesis of this pharmaceutical has been performed in good overall yield from commercially available 3-methoxyacetophenone.
Mangas-Sánchez
Juan
J
Departamento de Química Orgánica e Inorganica, Instituto Universitario de Biotecnología de Asturias, Universidad de Oviedo, c/ Julián Claveria s/n, Oviedo 33071, Spain.
Rodríguez-Mata
María
M
Busto
Eduardo
E
Gotor-Fernández
Vicente
V
Gotor
Vicente
V
D002175:Candida / Q000201:enzymology*; D002384:Catalysis; D008049:Lipase / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D048448:Phenylcarbamates / Q000138:chemical synthesis* / Q000737:chemistry; D000068836:Rivastigmine; D013237:Stereoisomerism
D048448:Phenylcarbamates; D008049:Lipase; D000068836:Rivastigmine