Synthesis of the C-Terminal Macrocycle of Asperipin-2a.

A synthetic approach to the C-terminal macrocycle of asperipin-2a is presented. Two epimers were prepared, possessing R- and S-configurations at the β-position of Tyr3. Comparison of NMR data of the natural product with these isomers and X-ray crystallographic data for one macrocycle support assignment of the 2 S,3 S -configuration of Tyr3. Key steps in the synthesis include a stereoselective benzylic oxidation of the tyrosine residue and Lewis-acid-catalyzed ring opening of the subsequently generated aziridine.