EXPERIMENTS TOWARDS THE TOTAL SYNTHESIS OF 5-MEMBERED D-RING ERGOT ALKALOID ANALOGS

The known tricyclic ketone, Kornfeld's ketone (5)1, has been prepared in a much improved yield by modification of the usual procedure from the commercially available indole-3-propionic acid. Direct condensation with N-methylaminopropionitrile yielded a derivative, 4-(N-methyl-N-2'-cyanoethyl)amino-1-benzyl-2, 2a,3,4-tetrahydrobenz[cd]indol-5H-(1H)-one which could not be cyclized to the desired five-membered D-ring ergot analogue. In a different approach the 4-methylamino derivative was prepared via the carbamate and the corresponding oxazolinone. However, introduction of the requisite side-chain for the construction of the D-ring failed. Finally in the presence of an amide substituent at C-4 of the tricyclic ketone two five-membered D-ring analogues were obtained under Cope's reaction conditions by introducing a two-carbon chain at C-5.