Synthesis of racemic and optically active codeine and morphine <i>via</i> the <i>N</i>‐formylnordihydrothebainones: (Chemistry of opium alkaloids, part X)

Abstract

Abstract Starting from 3,4,5‐trihydroxybenzoic acid (gallic acid), racemic 1‐(3,5‐dibenzyloxy‐4‐methoxybenzyl)‐1,2,3,4‐tetrahydro‐6‐methoxyisoquinoline (3, Scheme) was synthesized. Resolution with (‐)‐( S )‐malic acid yielded (+)‐( R )‐3. By a Birch reduction, followed by N ‐formylation, and by acid‐catalysed cyclization, we obtained racemic and optically active N ‐formyl‐2‐hydroxynordihydrothebainone (6) . 6 Was selectively converted into N ‐formyl‐2‐(1‐phenyltetrazol‐5‐yloxy)nordihydrothebainone (7) . Hydrogenolysis of (‐)‐7 and of racemic 7 yielded (‐)‐ N ‐formylnordihydrothebainone (8) and racemic 8, respectively. Previously we had converted the N ‐formyl derivative (8) in various ways into dihydrothebainone. The conversion into (‐)‐codeine and (‐)‐morphine is known.