SYNTHESIS AND ANALYSIS OF O, O'-DICARBOXYLATE (DIBENZYL) BISPILOCARPATES AS POSSIBLE PRODRUGS OF PILOCARPINE

As a part of a series of studies to develop prodrug derivatives of pilocarpine, the O,O'-succinyl (dibenzyl), O,O'-glutaryl (dibenzyl), O,O'-adipoyl (dibenzyl), O,O'-fumaryl (dibenzyl), and O,O'-terephthaloyl (dibenzyl) bispilocarpate fumarates were synthesized as a new class of pilocarpine prodrugs. The compounds were prepared from pilocarpic acid benzyl monoester by coupling two pilocarpic acid benzyl monoesters together with spacer chains by usual esterification methods. Liquid chromatography, thermospray liquid chromatography-mass spectrometry, high-resolution mass spectrometry, and NMR spectroscopy were applied to the identification and the purity evaluation of the synthetic products.