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Linaclotide is a 14-amino acid residue peptide approved by the FDA for the treatment of irritable bowel syndrome with constipation (IBS-C), which activates guanylate cyclase C to accelerate intestinal transit. Here we show a new method for the synthesis of linaclotide through the completely selective formation of three disulfide bonds in satisfactory overall yields via mild oxidation reactions of the solid phase and liquid phase, using 4-methoxytrityl (Mmt), diphenylmethyl (Dpm) and 2-nitrobenzyl (O-NBn) protecting groups of cysteine as substrate, respectively. [ABSTRACT FROM AUTHOR]

Abstract: Phosphinodepsipeptides are recognized as an important class of enzyme inhibitors as tetrahedrally structural transition-state analogues to natural peptides. A series of phosphinodepsipeptides was synthesized in satisfactory yields via pseudo-four-component condensation reaction of 2-(N-benzoxycarbonylamino)alkanamides/peptide amides, aldehydes, and aryldichlorophosphines, followed by alcoholysis with hydroxyl esters. [Copyright &y& Elsevier]

Both sulfonopeptides and phosphonopeptides are important analogs of naturally occurring peptides and have been widely used as enzyme inhibitors and haptens for producing catalytic antibodies due to their tetrahedrally structural features. A series of hybrid sulfonophosphinodipeptides composing of taurines and 1-aminoalkylphosphinic acids were first and conveniently synthesized in satisfactory to good yields via a Mannich-type reaction of N-benzyloxycarbonylaminoalkanesulfonamides, aldehydes, and aryldichlorophosphines, and subsequent hydrolysis. The current method provides an efficient and direct synthesis of hybrid sulfonophosphinodipeptides. [ABSTRACT FROM AUTHOR]