Effect of piperidine on benzylaspartyl peptides in solution and in the solid phase

Abstract

Basic conditions (e.g. piperidinolysis), used for the removal of the N~-9-fluorenylmethyloxycarbonyl group, lead to significant cleavage of side-chain benzyl esters of peptides containing benzylaspartyl residues both in solution and solid-phase syntheses; the intermediate imide derivative is slowly transformed to a mixture of piperidides.Recently a synthesis of thymosin-a, onp-nitrobenzhydrylamine resin was reported,l using benzyl esters for protection of sidechain carboxy groups. The temporary N"-9-fluorenylmethoxy-carb0ny1~9~ (Fmoc) protecting group was removed by piperidinolysis. During the purification of the crude thymosin-cc,, fractions corresponding to minor peaks in the elution profile obtained from DEAE-Sephadex A-25 column chromatography were shown to contain materials which could not be completely digested with leucine-aminopeptidase, suggesting that undesired reactions may have occurred during the synthesis.Knowing the general base-sensitivity of p-esters of aspartyl pep tide^^-^ we have examined the possibility that the repeti-

o-Boronato- and o-Trifluoroborato–Phosphonium Salts Supported by l-α-Amino Acid Side Chain

“…The feasibility and the effectiveness of the boronato–phosphonium derivatives 4 in peptide coupling was investigated by reaction of the amino derivative 4g , previously obtained by treatment of 4f with DABCO, with the benzyl-β-pentafluoro­phenate l -aspartate 12 (Scheme ). After 6 h in acetonitrile at 50 °C, the corresponding dipeptide 13 was obtained in 61% yield.…”