SYNTHESIS OF 7-SUBSTITUTED 6-DEMETHOXYTHEBAINES AND DIELS-ALDER REACTION OF 7-METHOXY-5-BETA-METHYL-6-DEMETHOXYTHEBAINE - (CHEMISTRY OF OPIUM-ALKALOIDS .41.)

Mesylation of 7-acetoxyneopine (4), followed by reductive cleavage of the acetyl group gave 6 alpha-O-mesyl-7 alpha-hydroxyneopine (6), in w hich the hydroxyl group was protected as a methoxymethoxy group. Elimi nation of the mesyl ester yielded 7-(methoxymethoxy)-6-demethoxythebai ne (7). For the 5 beta-methyl analogue, we started from 6-O-acetyl-7 a lpha-hydroxy-5 beta-methyl-neopine (5), which was converted into 9 via hydroxyl protection as a methoxymethoxy group and removal of the acet yl group. Mesylation and elimination gave 7-(methoxymethoxy)-5 beta-me thyl-6-demethoxythebaine (10). Hydrolysis of 7 and 10 afforded the sal utaridine analogue 11 and 5 beta-methyl-6-deoxyneopin-7-one (12), whic h were easily converted into the 7,7-dimethoxy-6-deoxyneopine analogue s 13 and 14. Elimination of methanol from 14 yielded the desired diene 15. Diels-Alder reaction of 15 with ethyl acrylate yielded exclusivel y the 8 beta-substituted 6 beta,14 beta-ethenomorphina 16, due to alph a-face approach. Cycloaddition of diene 15 with maleic anhydride gave the 6 alpha,14 alpha-ethenoisomorphinan 17 and the 6 beta,l4p-ethenomo rphinan 18 in a ratio of 5:4. The outcome of the Diels-Alder reactions is discussed in relation to the substituents at the 5 beta- and 7-pos itions combined with an asynchronous cycloaddition mechanism.