IS THERE ANOTHER COMMON INTERMEDIATE BEYOND CHORISMIC ACID IN THE SHIKIMATE PATHWAY - SYNTHESIS OF NYL)OXY]-6-HYDROXYCYCLOHEXA-1,4-DIENE-1-CARBOXYLIC ACID

As part of a search for mechanistic commonalities uniting the three ch orismate-processing enzymes of anthranilate, PABA, and isochorismate b iosynthesis, the title compound 9a, a highly labile allylic isomer of chorismic acid, was prepared by total synthesis. The synthetic route f eatured a new, Lewis-acid promoted opening of epoxides by diselenides leading to trans-hydroxy selenides. This remarkable reaction obviates the need to handle unpleasant selenols and simplifies the usual two-st ep anionic process involving in situ generation of alkali metal seleni des. Diene 9a underwent rapid acid-catalyzed aromatization and [3,3]-s igmatropic rearrangement. Claisen rearrangement of 9a (t(1/2) << 10 mi n at 4 degrees C) was much faster than that of chorismate, isochorisma te, aminodeoxychorismate, or aminodeoxyisochorismate, making conventio nal kinetic assays in the presence of shikimate branchpoint pathway en zymes impossible. Nevertheless, the rapid and regioselective Claisen r earrangement of 9a led to an alternative mechanistic rationale for the biosynthesis of aromatic amino acids such as m-carboxyphenylalanine a nd m-carboxytyrosine.