A Short Review of Synthetic Routes for the Antiepileptic Drug (R)-Lacosamide

Abstract

The disease epilepsy affects people of all ages and is due to a chronic neurological disorder in the brain. According to a report by the World Health Organization, epilepsy is one of the most common global neurological diseases. (R)-Lacosamide (Vimpat) was introduced by UCB Pharma in 2008 for the treatment of partial-onset seizures in patients suffering from epilepsy. This review summarizes all of the available synthetic strategies reported for (R)-lacosamide, which will help medicinal chemists in the further development of its synthesis.

Development of a Continuous Process for the Large-Scale Asymmetric Manufacture of (R)-3-Methoxy-2-(4-methylpiperazin-1-yl)propanoic Acid

“…These initial results, in parallel with the corroborating observations made in the literature, 9 allowed subsequent route design to be focused into the following key areas:…”

Direct, Enantioselective, and Nickel(II) Catalyzed Reactions of N‐Azidoacetyl Thioimides with Trimethyl Orthoformate: A New Combined Methodology for the Rapid Synthesis of Lacosamide and Derivatives

“…One of such compounds is the antiepileptic agent lacosamide (Scheme ). First synthesized in 1996, lacosamide and structurally related compounds show an important anticonvulsant activity for which they have recently received much attention . Despite such an interest, most of the synthetic approaches reported up to now rely on the appropriate treatment of d ‐serine or other starting materials from the chiral pool .…”

“…First synthesized in 1996, lacosamide [12] and structurally relatedc ompoundss how an important anticonvulsant activity [18] for which they have recently received much attention. [13] Despite such an interest, most of the synthetic approaches reported up to now rely on the appropriate treatment of d-serine or others tartingm aterials from the chiral pool. [18,19] Alternatively,afew syntheses involve kinetic resolution steps [20] or are based on asymmetric reactions applied to substrates containing the required carbon backbone.…”

“…We hereby describe our first resultso nt he enantioselective addition of N-azidoacetyl thioimides to trimethyl orthoformate and the application of this methodt ot he synthesis of lacosamide [12,13] and several related compounds as ap roof of concept (Scheme 1C).…”

Reações Multicomponente – Uma Ferramenta Valiosa na Descoberta e Produção de Fármacos

“…A lacosamida pode ser obtida através de diferentes metodologias, recentemente revistas na literatura [51]. Para além da abordagem multicomponente descrita no Esquema 3, escolhemos o exemplo de S. Stecko como uma abordagem de síntese passo--a-passo [52], já que neste exemplo é reportada uma descrição cuidada do procedimento experi-Esquema 9 -Síntese de praziquantel usando uma reação de Ugi de quatro componentes [49].…”