The influence glutamic acid in protonated b3 → b2 formation from VGEIG and related analogs

► b2 oxazolone formation requires a b3 anhydride intermediate in protonated VGEIG. ► The b3 VGEIG anhydride is an intermediate to formation of b3 macrocyclic structures. ► Data suggest that the b3 macrocycle is an 11-membered ring structure. ► Alpha proton scrambling is demonstrated in VXEIG analogs and a new pathway proposed.