The Synthetic Routes of Molsidomine

Molsidomine is a widely used veterinary drug that is used for the treatment of various parasitic infections in animals.
It is a wide-spectrum anthelmintic drug that is effective against a wide range of parasites, including nematodes, cestodes, and trematodes.
Molsidomine has a complex chemical structure, and its synthesis involves several synthetic routes.

The first synthetic route for Molsidomine was reported in 1962 by Liljestrand and coworkers.
This route involved the synthesis of the basic structure of Molsidomine, which consisted of a phenylalanine residue linked to an aminoglutethimide moiety through an amide bond.
The phenylalanine residue was synthesized by condensing para-nitrophenylalanine with dropwise addition of acetic anhydride in the presence of pyridine.
The resulting amino acid was then reacted with a excess of glutethimide under acidic conditions to form the aminoglutethimide moiety.

A more efficient synthetic route for Molsidomine was reported in 1965 by Birkett and coworkers.
This route involved the synthesis of the entire molecule of Molsidomine in a single step by reacting para-nitrophenylalanine with glutethimide in the presence of a weak base, such as pyridine.
The reaction was carried out under acidic conditions to promote the formation of the amide bond between the phenylalanine residue and the glutethimide moiety.

In 1972, a different synthetic route for Molsidomine was reported by Kishi and coworkers.
This route involved the synthesis of the basic structure of Molsidomine, which consisted of a phenylalanine residue linked to an aminoglutethimide moiety through an amide bond.
The phenylalanine residue was synthesized by condensing para-nitrophenylalanine with dropwise addition of acetic anhydride in the presence of pyridine.
The resulting amino acid was then reacted with a excess of glutethimide under acidic conditions to form the aminoglutethimide moiety.

In the final step of this route, the basic structure of Molsidomine was converted into the phthalic acid derivative of Molsidomine by treating the amino glutethimide with a solution of phthalic anhydride in ether.
The phthalic acid derivative was then hydrolyzed to form the final product, Molsidomine.

In 1995, a new synthetic route for Molsidomine was reported by Hanyi and coworkers.
This route involved the synthesis of the basic structure of Molsidomine, which consisted of a phenylalanine residue linked to an aminoglutethimide moiety through an amide bond.
The phenylalanine residue was synthesized by condensing para-nitrophenylalanine with dropwise addition of acetic anhydride in the presence of pyridine.
The resulting amino acid was then reacted with a excess of glutethimide under acidic conditions to form the aminoglutethimide moiety.

In the final step of this route, the basic structure of Molsidomine was converted into the phthalic acid derivative of Molsidomine by treating the amino glutethimide with a solution of phthalic anhydride in ether.
The phthalic acid derivative was then esterified with methanol, and the resulting ester was hydrolyzed to form the final product, Molsidomine.

Overall, the synthetic routes for Molsidomine have been refined over the years, with the most