Lanthionine Peptides by S-Alkylation with Substituted Cyclic Sulfamidates Promoted by Activated Molecular Sieves: Effects of the Sulfamidate Structure on the Yield

A green and efficient method for preparing lanthionine peptides by a highly chemoselective and stereochemically controlled procedure is presented. It involves an S-alkylation reaction, promoted by activated molecular sieves, on chiral cyclic sulfamidates, both N-protected and unprotected. Of note, the reaction yield was high also for cyclic sulfamidates bearing a free amine group, while other strategies failed to achieve a ring-opening nucleophilic reaction with N-unprotected substrates. To prove the feasibility of the procedure, the synthesis of a thioether ring B mimetic of the natural lantibiotic haloduracin β was performed.We are thankful for the support of the Ministerio de Ciencia, Innovacion y Universidades (RTI2018-099592-B-C21 and RTI2018-099592-B-C22 projects) and the Ministerio de Economia y Competitividad (RYC-2013-14706 to G.J.-O. and FPI fellowship to P.T.)