Silica-supported fluoroboric acid (HBF4-SiO2) catalyzed highly productive synthesis of thiomorpholides as activators of L-asparaginase as well as the antioxidant agent

An efficient solvent-free procedure for the synthesis of thiomorpholides in the presence of a catalytic amount of solid-supported fluoroboric acid (HBF4-SiO2) is described. The advantages of this method are high yields, short reaction times, ease of product isolation, low cost, and the catalyst can be recycled for a number of times without significant loss of activity. Three thiomorpholides possessing electron-donating group (4c, 4g, and 4h) were exhibiting excellent stimulatory activities against Erwinia carotovora L-asparaginase. The most potent activator, compound 4h displayed the following kinetic parameters, K-m = 75 mu M and V-max = 1000 mu mol mg(-1) min(-1) and K-A = 0.985 mu M. Furthermore, these compounds (4g, 4h, 4c, 4f, 4a, and 4d) have also shown promising 2,2'-diphenyl-1-picrylhydrazyl (DPPH) reducing antioxidant activity (21-36%) at 1 mM concentration as compared to standard butylated hydroxyl anisole (72% at 1 mM). (C) 2010 Published by Elsevier Ltd.