Scale-up synthesis of mesna using alkyl trithiocarbonate approach

Abstract

Mesna is in a class of drugs known as chemoprotectants. Mesna is used for the prevention of urothelial toxicity in patients being treated with the antineoplastics ifosfamide or cyclophosphamide. In this study, a new method for synthesis of mesna from 1,2-dichloroethane using trithiocarbonate salt intermediate was continuously developed by the scale of 100g per batch. The synthesis was carried out in 3 steps: Firstly, sodium 2-chloroethanesulfonate was prepared from 1,2-dichloroethane by Strecker reaction. Secondly, sodium 2-chloroethanesulfonate was reacted with sodium trithiocarbonate, followed by acidification to pH 1.43 by H2SO4 or HCl solution. Finally, mesna was obtained by adjusting pH to 6.6 with 1.5 M NaOH solution. The product was purified by crystallization from 96% ethanol. The overall yield of the synthesis process from 1,2-dichloroethane was 38.85 % based on sodium sulfite. The structures of the compounds were defined by IR, MS and NMR spectra data analysis. The product has met all quality requirements of British Pharmacopoeia 2015 therein the content of dried substance was 98.8%.