Towards new camptothecins.: Part 3:: Synthesis of 5-methoxycarbonyl camptothecin

The synthesis of two camptothecin analogs substituted by a carbonyl function on position 5 of cycle C was realized. New conditions were studied to obtain the E-lactone ring of these heterocycles. These compounds were obtained from the reaction of Bredereck's reagent with indolizines derived from pyroglutamic acid. This yielded dimethylaminovinyl groups whose oxidation by NaIO4 yielded ketones. The indolizinones obtained were reacted in Friedlander condition, to give the scaffold of the desired camptothecins. (c) 2006 Elsevier Ltd. All rights reserved.