Synthesis of neopine and its 5β- and 7-substituted derivatives (chemistry of opium alkaloids, part XL)

Article abstract of DOI:10.1002/recl.19931121103

Heating 14β-bromocodeine (3) with methanol and triethylamine yielded 6α,7α-epoxy-6-deoxyneopine (5).The epoxide 5 was reduced to neopine (7) with lithium aluminium hydride, whereas reaction of 5 with sodium methoxide gave 7β-methoxyneopine (9).Similar reactions were performed with 14β-bromo-5β-methylcodeine (4), yielding the corresponding 5β-methyl derivatives 6, 8 and 10.Acetylation of 3 and 4 gave 6α-O-acetyl-14β-bromocodeine (11) and its 5β-methyl analogue 12, respectively, from which the ortho esters 13 and 14 were obtained after treatment with methanol.Acid hydrolysis of 13 or, better, solvolysis of 11 in water yielded a mixture of 6α-O-acetyl-7α-hydroxyneopine (15) and 7α-acetoxyneopine (17).Under the same conditions 12 and 14 gave the 5β-methyl analogues 16 and 18.