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Synfacts 2015; 11(1): 0008
DOI: 10.1055/s-0034-1379644
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of (R)-Rasagiline via Dynamic Kinetic Resolution

Contributor(s):
Philip Kocienski
Ma G, Xu Z, Zhang P, Liu J, Hao X, Ouyang J, Liang P, You S, * Jia X. * Shenyang Pharmaceutical University, P. R. of China
Novel Synthesis of Rasagiline via a Chemoenzymatic Dynamic Kinetic Resolution.

Org. Process Res. Dev. 2014;
18: 1169-1174
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Publication History

Publication Date:
15 December 2014 (online)

 
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Key words

rasagiline - monoamine oxidase B inhibitors - dynamic kinetic resolution - racemization - Candida antarctica lipase B - hydrogen borrowing

Significance

Rasagiline mesylate (Azilect®) is a selective monoamine oxidase B inhibitor that is administered as initial monotherapy in early ­Parkinson’s disease and as adjunct therapy to levodopa in moderate-to-advanced disease. The key step in the synthesis depicted is the dynamic kinetic resolution of racemic 1-aminoindan A catalyzed by immobilized Candida antarctica lipase B (CALB) together with a palladium racemization catalyst – a process that could be conducted in a concentration of up to 200 g/L.


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Comment

The palladium nanocatalyst Pd/AlO(OH) racemizes the amine via an imine intermediate (hydrogen borrowing). Racemization was complete in four hours using only 0.5 mol% of palladium in toluene at 70 °C. The catalyst was prepared as palladium nanoparticles entrapped in aluminum hydroxide according to the procedure of Y. Kim et al. (Tetrahedron Lett. 2010, 51, 5581). The chemoenzymatic catalyst system could be recycled 5–6 times.


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