SYNTHESIS OF HYL-6,7-DEHYDRO-3,14-DIHYDROXY-4,5-ALPHA-EPOXY-6,7 4',5'-THIAZOLOMORPHINAN FROM NALTREXONE[1]/

Fusion of an azole moiety at C-6 and C-7 of naltrexone (1) is illustra ted by the synthesis of the title compound 8. Bromination of 3-O-methy lnaltrexone led to the 1,7 alpha-dibromo derivative which reacted with thiourea to attach the 2-aminothiazole ring to C-6 and C-7 of naltrex one. After converting the amino and alcohol groups to trimethylsilyl d erivatives, the aromatic bromo group was removed by halo-lithium inter change with butyllithium, followed by hydrolysis with water. In the fi nal step of the synthesis, the methyl ether was cleaved by boron tribr omide to generate 8. An alternate synthesis of 8 commenced with 3-O-ac etylnaltrexone (9). Bromination of 9 in acetic acid in the presence of hydrobromic acid produced a mixture of 3-O-acetyl-7 alpha-bromonaltre xone (10) and 7 alpha-bromonaltrexone (11), both, as hydrobromides. Re action of this mixture with thiourea furnished 8 (62% from 1). While H -1 and C-13 chemical shifts of all compounds are reported, those of 11 hydrobromide and 8 dihydrochloride were established unequivocally.