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. (C) 2000 Elsevier Science Ltd. All rights reserved.