Chemoenzymatic synthesis of rivastigmine via dynamic kinetic resolution as a key step

Kiwon Han; Cheolwoo Kim; Jaiwook Park; Mahn-Joo Kim

doi:10.1021/jo9027374

Chemoenzymatic synthesis of rivastigmine via dynamic kinetic resolution as a key step

J Org Chem. 2010 May 7;75(9):3105-8. doi: 10.1021/jo9027374.

Authors

Kiwon Han¹, Cheolwoo Kim, Jaiwook Park, Mahn-Joo Kim

Affiliation

¹ Department of Chemistry and Bionanotechnology Center, Pohang University of Science and Technology, San-31 Hyojadong, Pohang 790-784, Korea.

PMID: 20345141
DOI: 10.1021/jo9027374

Abstract

A practical and efficient procedure for the synthesis of rivastigmine was developed. This procedure includes dynamic kinetic resolution using a polymer-bound ruthenium complex and a lipase in combination as a key step. Enantiopure (-)-rivastigmine was obtained from commercially available 3'-hydroxyacetophenone via five steps in overall 57% yield.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetophenones / chemistry
Catalysis
Cholinesterase Inhibitors / chemical synthesis*
Enzymes, Immobilized / chemistry
Fungal Proteins
Kinetics
Lipase / chemistry
Models, Chemical
Molecular Structure
Phenylcarbamates / chemical synthesis*
Rivastigmine
Ruthenium / chemistry

Substances

Acetophenones
Cholinesterase Inhibitors
Enzymes, Immobilized
Fungal Proteins
Phenylcarbamates
Ruthenium
Lipase
lipase B, Candida antarctica
Rivastigmine
3'-hydroxyacetophenone