John Fairhurst

The synthesis and biological activity of some known and putative metabolites of the atypical antipsychotic agent olanzapine (LY170053)

Abstract 4′-N-desmethyl olanzapine (2), olanzapine 4′-N-oxide (3) and 2-hydroxymethyl olanzapine (5), have been prepared and their pharmacology compared to that of the parent compound olanzapine (1). The 4′-N-quaternary glucuronide (8) has also been prepared.

Synthesis of the 2,3,4-trisubstituted indole fragments of nosiheptide and glycothiohexide

Two routes to the protected 4-hydroxymethyl-3-methylindole-2-carboxylate fragment 17 of the thiopeptide antibiotic nosiheptide are described starting from methyl 4-methylindole-2-carboxylate 11, itself prepared in two steps, or from 3-amino-4-chlorobenzoic acid 26. The first route can be adapted to the synthesis of a fragment of the related antibiotic glycothiohexide-alpha, the 3,4-bis(hydroxymethyl)indole-2-carboxylate in which the two hydroxymethyl groups are differentiated as in indole 19 or the lactone 20.