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[reaction in text] A new method for the synthesis of selenocysteine derivatives and selenocysteine-containing peptides is described. Fmoc-Se-p-methoxybenzylselenocysteine (1) was prepared and used for solid-phase synthesis of peptides with an N-terminal unprotected selenocysteine. Subsequent native chemical ligation with a peptide thioester provided a 17-mer that corresponds to the C-terminus of ribonucleotide reductase with selenocysteine in place of cysteine.

[reaction: see text]. Protein and peptide conjugates such as glycopeptides, prenylated peptides, and lipopeptides play essential roles in biology. A rapid and convergent entry into a variety of these compounds is described. The methodology involves the introduction of a dehydroalanine into peptides and subsequent chemoselective conjugate addition of an appropriate thiolate nucleophile, including farnesylthiolate or thioglycosides.

[reaction: see text] Peptides containing (E)- and (Z)-3-fluorodehydroalanine have been prepared from serine via a fluoro-Pummerer rearrangement. The resulting electrophilic moieties may be useful affinity labels for the identification of the targets of dehydroamino acid containing natural products that act by covalent mechanisms.

Useful methodology is described for the synthesis of dehydroalanine residues (II) within peptides. The unnatural amino acid (Se)-phenylselenocysteine (I) can be incorporated into growing peptide chains via standard peptide synthesis procedures. Subsequent oxidative elimination affords a dehydroalanine at the desired position. The oxidation conditions are mild and tolerate functionalities commonly found in peptides, including variously protected cysteine residues. To illustrate its utility, cyclic lanthionines have been synthesized by this method.