6,7α:14,7β-Bis(oxymethylene)dihydromorphines

Article abstract of DOI:10.1021/jo00159a006

6,7α:14,7β-Bis(oxymethylene)morphinans, which contain seven ring structures within the molecule, were synthesized from 14-hydroxydihydrocodeinone (1).Conversion of 1 to 7,7-bis(hydroxymethyl)-4,5α-epoxy-3-methoxy-17-methylmorphinan-6β,14-diol (2) and then reaction with 1,2 equiv of p-TsCl gave 7α-tosyloxymethylene derivative 3.Base treatment of 3 gave 7,7-(oxydimethylene) compound 4 which was oxidized to the C6-oxo derivative 5.Ditosylation of 2 followed by base treatment resulted in formation of 7α-<(tosyloxy)methyl>-14,7β-(oxymethylene)morphinan-6β-ol 7 which was converted to the 3-hydroxy-7α-methyl-6-oxo derivative 10.Displacement of the tosyloxy group in 7 by the 6β-ol resulted in the formation of 6β,7α:14,7β-bis(oxymethylene)morphinan 11.Inversion of the configuration at the C6-hydroxy by oxidation to 14 followed by hydride reduction and base treatment gave 16, the 6α,7α analogue of 11.Treatment of 14 with BBr3 gave 3-hydroxy-7α-(bromomethylene)morphinan 17 which was reduced with NaBH4 and ring closed to 6α,7α:14,7β-bis(oxymethylene)-4,5-epoxy-17-methylmorphinan-3-ol (19).