SYNTHESIS OF NEOPINE AND ITS 5-BETA-SUBSTITUTED AND 7-SUBSTITUTED DERIVATIVES - (CHEMISTRY OF OPIUM-ALKALOIDS .40.)

Keating 14 beta-bromocodiene (3) with methanol and triethylamine yield ed 6 alpha,7 alpha-epoxy-6-deoxyneopine (5). The epoxide 5 was reduced to neopine (7) with lithium aluminium hydride, whereas reaction of 5 with sodium methoxide gave 7 beta-methoxyneopine (9). Similar reaction s were performed with 14 beta-bromo-5 beta-methylcodeine (4), yielding the corresponding 5 beta-methyl derivatives 6, 8 and 10. Acetylation of 3 and 4 gave 6 alpha-O-acetyl-14 beta-bromocodeine (11) and its 5 b eta-methyl analogue 12, respectively, from which the ortho esters 13 a nd 14 were obtained after treatment with methanol. Acid hydrolysis of 13 or, better, solvolysis of 11 in water yielded a mixture of 6 alpha- O-acetyl-7 alpha-hydroxyneopine (15) and 7 alpha-acetoxyneopine (17). Under the same conditions 12 and 14 gave the 5 beta-methyl analogues 1 6 and 18.