Conversion of the naturally occurring amide alkaloids into O5 benzo[c]phenanthridinium alkaloids. A new synthetic sequence to antitumour benzo[c]phenanthridine alkaloids

Abstract

Cyclisation of methyl integriamide (17a) and methyl isoarnottianamide (17b) by the Bischler–Napieralski reaction gave the naturally occurring O5, benzp[c]phenanthridine alkaloids, chelirubine (5a) and chelilutine (5b), respectively; this was extended to give a generally applicable, versatile synthesis of benzo[c]phenanthridine alkaloids from 2-aryl-3,4-dihydronaphthalen-1(2H)-ones (13). Treatment of the tetralones (13) with methylamine and titanium tetrachloride followed by sodium borohydride provided the cis-2-aryl-N-methyl-1,2,3,4-tetrahydro-1-naphthylarmines (14) which were converted into the N-formyl derivatives (15) with freshly prepared chloral in good yields. Dehydrogenation of the resulting formamides (15) with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) gave the fully aromatised amides corresponding to methyl integriamide (17a). Bischler–Napieralski reaction of these amides (17) furnished the desired quaternary benzo[c]phenanthridine alkaloids (5).