Synthesis of (S)-Rivastigmine

doi:10.1055/s-0030-1257746

Synfacts 2010(8): 0853-0853
DOI: 10.1055/s-0030-1257746

Synthesis of Natural Products and Potential Drugs

Synthesis of (S)-Rivastigmine

Contributor(s):Philip Kocienski

K. Han, C. Kim, J. Park*, M.-J. Kim*
Pohang University of Science and Technology, Korea
Chemoenzymatic Synthesis of Rivastigmine via Dynamic Kinetic Resolution as a Key Step
J. Org. Chem. 2010, 75: 3105-3108

Abstract

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Key words

rivastigmine - dynamic kinetic resolution - lipases - racemization

Significance

Rivastigmine (Exelon^®) is an acetylcholinesterase inhibitor that is prescribed for the treatment of mild to moderate dementia in patients with Alzheimer’s disease and Parkinson’s disease. The key step in the synthesis depicted is a dynamic kinetic resolution of the benzylic secondary alcohol B involving a lipase (Novozyme 435) coupled with a polymer-bound racemization catalyst (C).

Comment

The polymer-bound racemization catalyst C was prepared by heating a polymer-bound benzoyl chloride with [Ph₄(η⁴-C₄CO]Ru(CO)₃ in toluene for one day. The catalyst can be recycled several times. The enzymatic resolution was performed on a 1 mmol scale. For an alternative chemoenzymatic synthesis of rivastigmine, see: J. Mangas-Sánchez et al. J. Org. Chem. 2009, 74, 5304.

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