Selective oxidation of linear and cyclic peptides by dioxiranes

ORGN 140

Maria Rosaria Rella and Paul G. Williard, paul_williard@brown.edu. Department of Chemistry, Brown University, 324 Brook Street, Providence, RI 02912
Representative Boc-protected and acetyl-protected peptide methyl esters bearing alkyl side chains undergo effective oxidation using methyl(trifluoromethyl)dioxirane 1b under mild conditions. We observe a protecting group dependency in the chemoselectivity displayed by the dioxirane 1b: N-hydroxylation occurs in the case of the Boc-protected peptides, and side chain hydroxylation takes place in the case of acetyl-protected peptides. Both are attractive transformations since they yield derivatized peptides that serve as valuable synthons. Moreover, biomimetic oxyfunctionalizations of bioactive cyclic peptides by dioxiranes can be achieved. These selective side chain modifications might improve the solubility and/or the bioavailability of the parent cyclic peptides. Besides, the actual isolation of oxyfunctionalized derivatives of cyclic peptides should provide the opportunity to test for their enhanced or even widely different bioactivity with respect to the parent molecule.