Total Synthesis of the Fumiquinazoline Alkaloids:  Solution-Phase Studies¹

Biomimetic total syntheses of glyantrypine, fumiquinazoline F, fumiquinazoline G, and fiscalin B were achieved in four steps from tryptophan methyl ester. In the key step, the anthranilamide residue in a linear tripeptide is dehydrated to a benzoxazine by reaction with triphenylphosphine, iodine, and a tertiary amine. The benzoxazines subsequently undergo rearrangement to the natural products via an amidine intermediate. This dehydrative oxazine to quinazoline route is applicable to a broad range of N-acylanthranilamides, including sterically hindered cases.