Synthesis of the Calophyllum coumarins. Part 2

Abstract

Synthetic routes leading to the synthesis of the natural 4-phenyl, 4-propyl and 4-methyl coumarins isolated from Calophyllum sp. are presented. 4-Aryl or -alkyl, 8- and 6-acyl 5,7-dihydroxy coumarins were chromenylated and then methylated at the 5 or 7 positions. A 4-step hydrobromination–bromination–double dehydrobromination sequence converted the 2-methylbutanoyl side chain into the (E)-2-methylbut-2-enoyl (tigloyl) group to give calophyllolide, oblongulide, their natural 4-propyl analogue and the corresponding regioisomers. Demethylation and cyclisation of the tigloyl group gave inophyllums C and E, tomentolides A and B, and calanolide D. Sodium boranuide reduction of the 2,3-dimethylchromanone ring afforded inophyllums A, B, D and P, soulattrolide, calanolides A-C, costatolide, and cordatolides A and B. The structures of calanolides C and D, oblongulide and apetatolide have been reassigned. The previously unknown stereochemistry about the 2,3-dimethylchromanone ring of tomentolides A and B has been established as trans.