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Studies on amino acids and peptides-III. 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide, , as a new racemization free coupling reagent in peptide synthesis

1982; Elsevier BV; Volume: 38; Issue: 22 Linguagem: Inglês

10.1016/0040-4020(82)80104-x

1464-5416

U. V. Pedersen, M. Thorsen, Ezz El-Din A.M. El-Khrisy, Kevin Kuhlmann Clausen, S.‐O. LAWESSON,

Organophosphorus compounds synthesis

The easily accessible 2,4-bis (4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide, LR, has been reacted with salts of N-protected amino acids 1 (Z-Gly-OH, Boc-Gly-OH, Boc-S-Ser(Bzl)-OH, Boc-S-Tyr(Bzl)-OH, Z-S-Arg(Z2)-OH, and Z-S-Pro-OH), at room temperature in CH2Cl2 to give the intermediates 2, mixed anhydrides. When 2 is treated with two moles of a base and one mole of the salt of an amino acid ester 3 (TosOH·H-Gly-OBzl, HCl·H-Gly-OBzl, HCl·H-Gly-OEt, and HCl·H-S-Phe-OtBu) at 0°C, the expected peptide 4 is isolated in high yields. LR is also found to be a useful reagent in a fragment coupling between Z-Gly-S-Ala-OH and TosOH·H-S-Leu-OBzl). This tripeptide was tested by means of HPLC (deprotection and amino acid analysis according to Izumiya was not necessary), and no epimerization (<0.7 %) was observed.