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

Abstract

AbstractHeating 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.