The elimination of H,O from serine residues in peptides was found to be feasible by the following two steps: 0-acylation with AcCl/pyridine in CH2CI, and treatment with an imidine base (DBU or DBN) in THF in the presence of large amounts of LiC104 (10 examples). Other Li salts such as LiBr and LiCl can also be used. No epimerization of the amino acid residues in the peptide could be detected under these conditions. Thus, a simple method for the preparation of peptides with dehydroalanine residues in high yield, directly from serine-containing precursors, is available. . In 1989, we discovered a dramatic effect of LiCl and other inorganic salts on the solubility of peptides in THF [6]. The changes of the peptide structure by LiCl were demonstrated for cyclosporin A in THF solution, using NMRspectroscopic methods [7]. The effect was exploited for improvements in the solution [8] and solid-phase [9] peptide synthesis of certain amino-acid sequences. In the course of the latter work, we found that peptides can be detached from resins -without removing acid-labile protecting groups -by transesterification using the imidine base DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) in the presence of LiBr in alcohols [lo]. When carrying out tests to learn, whether these conditions are compatible with the protecting groups commonly employed in peptide synthesis, we found that serine moieties are dehydrated by DBU/LiCl in the presence of 4-A molecular sieve, albeit slowly and in poor yields [l I]. This was the start of a project, the results of which are reported herein.Peptides A containing dehydroamino acids have been studied for a long time (Scheme I ) . They are normally made by incorporating a dehydroamino-acid residue into a peptide (E +A) [ 121 [ 131, and there are various methods of preparing suitable derivatives for this purpose (for reviews, see [14][15][16][17]), such as dehydration of serine and threonine (E'+E) [18][19][20][21][22][23][24], N-chlorinationldehydrochlorination of an amino-acid derivative ( E + E ) [25-281, or Wittig-Horner olefination using tl -phosphonylated glycine precursors (F+E) [29]. For further methods of preparing dehydroamino acids, we can only refer ') Part of the projected Ph. D. thesis of T.S., ETH-Zurich. We gratefully acknowledge a stipend given to T.S. by the Verband der Chemischen Industrie (D-Frankfurt).
