Synthesis of novel indole analogues of mycophenolic acid as potential antineoplastic agents

The expedient synthesis of three novel indole analogues, 2a-c, of mycophenolic acid is described, which involved as the key steps both the Et₂O.BF₃ catalyzed amino-Claisen rearrangement of N-allylindoline to 7- allylindoline and the ortho ester Claisen rearrangement of the allylic alcohol 12 to the methyl ester 14. The installation of the substituents at the C-3 position in 2b and 2c was accomplished via Vilsmeier formylation and subsequent oxidation aminolysis or oxidation methoxylation. The synthetic approach described possesses general usefulness. The analogue 2b showed significant, reproducible antitumor activity.