REINVESTIGATION OF SYNTHESIS OF ENOXAPARIN UNDER PTC CONDITIONSAbstract
Heparin is a mixture of glycosaminoglycan (GAG) chains originating from the porcine intestinal mucosa. It is used therapeutically as an anticoagulant for the treatment and prevention of thrombosis. Glyco-saminoglycans such as heparin (H) and heparan sulfate (HS) are considered attractive therapeutic agents because they modulate many biological processes and have been implicated in numerous pathologies, including cardiovascular, cancer, inflammation, metabolic, and neurodegenerative diseases and viral infections. These biological functions are believed to be dependent on the interaction of these linear polysaccharides with key proteins such as growth factors, cytokines, proteases, adhesion proteins, lipid binding proteins, etc., which have a heparin-binding domain in common and are termed heparin binding proteins (HBPs). The variability in unfractionated heparin’s pharmacokinetic properties and pharmacological effects led to the development of low MW heparin (LMWH), which is a degraded product of heparin using chemical or enzymatic cleavage techniques. The most common form of LMWH in the U.S. is enoxaparin, which is produced by β-eliminative cleavage of the benzyl esters of porcine mucosal heparin under alkaline conditions. This cleavage process leads to the generation of unnatural structures in enoxaparin. We present herein the purification strategies used to generate hexasaccharide that was further evaluated in vitro for their affinity for these protein targets, as well as heparanase inhibition. The hexasaccharide contains the same (L-Iduronic acid, D-Glucosamine) carbohydrate backbone but varying substitution patterns. We present here a new purification process of Enoxaparin with good yield.
P. Venkatanarayana, B. Prasanna * and N. Seelama
Department of Chemistry, Chaitanya (Deemed to be University), Kishanpura, Hanamkonda, Warangal, Telangana, India.
09 March 2020
10 June 2020
28 June 2020
01 March 2021