INTEGRATION OF A HIGHLY SELECTIVE DEMETHYLATION OF A QUATERNIZED ERGOLINE INTO A ONE-POT SYNTHESIS OF PERGOLIDE

We have developed a high-yielding one-pot synthesis of pergolide (10) from dihydrolysergol (1), which was isolated as pergolide mesylate (6, Permax), a semisynthetic ergot alkaloid marketed for the adjunctive t reatment of Parkinson's disease, The process involved the formation of quaternized amine intermediates, followed by a highly selective demet hylation and thioether formation via thiomethoxide ion, A novel tandem chromatography procedure was used to remove closely related byproduct s, which included an unexpected and unusual thiomethyl ether homologue of pergolide.