ON THE STABILITY OF S-(ALKYLSULFANYL)CYSTEINE DERIVATIVES DURING SOLID-PHASE SYNTHESIS

N-Acetyl-S-(alkylsulfanyl)cysteine benzyl esters were synthesized as m odels for N-acylated S-(alkylsulfanyl)cysteine residues linked via an ester bond to a solid phase. The S-protections involved were: the ethy lsulfanyl, the well-established tert-butylsulfanyl and the newly devel oped tritylsulfanyl group. We investigated the chemical behaviour of t he disulfides in reagents commonly applied in solid-phase peptide synt hesis using the Fmoc strategy (Fmoc SPPS). It was found that the trity lsulfanyl group as a thiol protection is comparable with the tert-buty lsulfanyl group in these respects. It is stable in trifluoroacetic aci d and is rapidly reduced by thiols and phosphines. For all three cyste ine esters rapid racemization was observed in piperidine (25%) in DMF, the amides being chirally stable. The demonstrated chiral instability of cysteine esters has consequences for the solid-phase synthesis of peptides using the Fmoc protocol.