Synthesis of oligomers of trans-(4S,5R)-4-carboxybenzyl 5-methyl oxazolidin-2-one:: An approach to new foldamers

The synthesis of two oligomers containing three and four residues, respectively, of trans-(4S,5R)4-carboxy 5-methyloxazolidin-2-ones is described. The monomer is obtained by starting from benzyl-N-Boc-(3R)-aminobutanoate, by cyclization into the corresponding trans-(2S,3R)-2-carboxybenzyl3-methyl-N-Boc-aziridine and rearrangement of the product to trans-(4S,5R)-4-carboxybenzyl-5methyloxazolidin-2-one, catalyzed by Sn(OTf)(2). The oligomers are synthesized by activating the carboxy group as its pentaflourophenyl ester. The trimer and the tetramer are obtained in good yield, and their H-1 NMR spectra suggest that these molecules fold in ordered structures, where the C-4 hydrogen of a ring is always close to the carbonyl of the next ring. This result shows that the 4-carboxy-5-substituted-oxazolidin-2-one are a new class of pseudoprolines which fully control the formation of a Xaa(i-1)-Pro(i) peptide bond in the trans conformation and are complementary to the pseudoprolines obtained from cyclocondensation of cysteine, serine, or threonine and aldehydes or ketones, which strongly favor the Xaai-1-Proi peptide bond in the cis conformation.