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Synfacts 2013; 9(1): 0012
DOI: 10.1055/s-0032-1317717
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Pregabalin

Rezensent(en):
Philip Kocienski
Yu H.-J, Shao C, Cui Z, Feng C.-G, * Lin G.-Q. * Shanghai Institute of Organic Chemistry, P. R. of China
Highly Enantioselective Alkenylation of Cyclic α,β-Unsaturated Carbonyl Compounds as Catalyzed by a Rhodium–Diene Complex: Application to the Synthesis of (S)-Pregabalin and (–)-α-Kainic Acid.

Chem. Eur. J. 2012;
18: 13274-13278
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Publikationsverlauf

Publikationsdatum:
17. Dezember 2012 (online)

 
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Key words

pregabalin - kainic acid - Hayashi–Miyaura asymmetric conjugate addition - rhodium catalysis - alkenyl trifluoroborates

Significance

Pregabalin (Lyrica®) is a lipophilic GABA analogue that is prescribed for the treatment of epilepsy. This short, small-scale synthesis of pregabalin features a highly enantioselective asymmetric conjugate addition of the alkenyl tri­fluoroborate B to the α,β-unsaturated lactam A catalyzed by a rhodium complex incorporating the chiral bicyclo[3.3.0]octa-2,5-diene ligand L.


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Comment

A further 17 examples of this new variant of the Hayashi–Miyaura asymmetric conjugate addition reaction are reported using six α,β-un­saturated carbonyl substrates and ten alkenyl tri­fluoroborates. The asymmetric conjugate addition was also applied to the synthesis of the potent neuroexcitatory agent α-kainic acid (seven steps, 40% overall yield).


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