Synthesis of ultra-short-acting neuromuscular blocker GW 0430: A remarkably stereo- and regioselective synthesis of mixed tetrahydroisoquinolinium chlorofumarates

[GRAPHICS] The stereo- and regioselective synthesis of ultra-short-acting nondepolariz ing neuromuscular blocker GW 0430 (5a) is described. Key steps involved the enantioselective transfer hydrogenation of imine 8 employing Noyori's cata lyst, the stereoselective crystallization and methanolysis of trans-betaine s 11 and 12, and the stereo- and regioselective trans elimination of hydrog en chloride from 14, The latter transformation allowed complete control of the position of the chloro substituent and stereochemistry at the double bo nd of the linker in 15.