The Synthetic Routes of Lacosamide

Lacosamide is an antiepileptic drug that is widely used to treat various types of epilepsy.
It is a synthetic compound that has been derived from natural sources, and its synthesis has undergone several modifications over the years.
The synthetic routes of lacosamide have evolved to become more efficient, cost-effective, and environmentally friendly.
In this article, we will explore the different synthetic routes of lacosamide and their significance in the chemical industry.

The first synthetic route for lacosamide was reported in 1996 by Targosz and co-workers, who synthesized the compound using a twelve-step sequence from the naturally occurring amino acid, L-pipecolic acid.
This route involved several protecting group manipulations and chemical transformations, including alkylation, acylation, and hydrolysis.
The authors also reported the absolute configuration of the compound using circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy.

However, this route was not very efficient, and an alternative synthetic route was later developed by Hiyama and co-workers in 1998.
This synthetic route involved a five-step sequence starting from the commercially available 2-oxo acid, oxazolidin-2-one, which was then converted into the key intermediate, N-(2,6-dimethylphenyl)acetamide.
This intermediate was then further transformed into lacosamide using a series of chemical reactions, including hydrolysis, alkylation, and condensation.
This route was found to be more efficient and cost-effective than the earlier route.

In 2001, another alternative synthetic route for lacosamide was reported by Bielawski and co-workers.
This route involved a six-step sequence starting from the readily available starting material, cyclohexanone.
The authors used several chemical transformations, including Grignard reaction, alkylation, and hydrolysis, to synthesize the compound.
This route was found to be simple, efficient, and economical, and it provides a convenient access to lacosamide with high yield and good purity.

In recent years, several other synthetic routes for lacosamide have been reported in the literature.
For example, in 2017, Zheng and co-workers reported a one-pot domino reaction for the concise synthesis of lacosamide.
This route involved the sequential coupling of two Tamarind-derived amino acids, followed by a domino reaction with a phenylalanine derivative to afford lacosamide.
This route was found to be efficient and atom-economical.

In 2019, Zhang and co-workers reported a simple and efficient synthesis of lacosamide via a four-step sequence starting from the readily available starting material, thiophene-2-carboxylic acid.
The authors used a series of chemical transformations, including condensation, nitration, and reduction, to synthesize the compound.
This route was found to be simple and cost-effective, and it provides a convenient access to lacosamide with high yield and good purity.

In addition to the above-mentioned synthetic routes, there are several other methods that have been reported in the literature for the synthesis of lacosamide.
For example, in 2012, Zhao and co-workers reported a green synthetic route for lacosamide using microwave-assisted hydrolysis.
This route involved the hydrolysis of a commercially available starting material, N-acetyl-L-leucine amide, using microwave irradiation.
The authors found that this method reduced the reaction time and solvent usage, and it was found to be an environmentally friendly method for the synthesis of lacosamide.

In conclusion, the synthetic routes of lacosamide have evolved over the years, and several methods have been reported in the literature.
The different synthetic routes offer several advantages, including efficiency, cost-effectiveness, and environmental friendliness.
These routes provide a convenient access to lacosamide, which is widely used in the treatment of