Synthesis from thebaine of 10-oxothebaine, potentially a precursor for κ-selective opiates

Abstract

Thebaine 3 has been converted in an improved yield (72%), with tetranitromethane, oxygen and ammonia, into the 14β-nitro 8α, 10α-epidioxide 4, which reacted with base to give the known 14β-nitro-10-oxo compound 7. Reduction of this nitro compound with tributyltin hydride gave the 8β-hydroxy-10-oxodihydrothebaine 8, which was dehydrated with phosphorus oxychloride to give 10-oxothebaine 9. As expected, this conjugated diene reacted with but-3-en-2-one to form a Diels–Alder cycloadduct 10, the 10-oxo derivative of thevinone 11, the precursor of a well known series of opiate analgesics. Unexpectedly, the epidioxide 4 was found to isomerise cleanly on activated alumina to give the 8α, 10α-epoxy acetal 5, in which a peroxide oxygen has been inserted into the 7,8-bond of the bridged peroxide 4.