DIPEPTIDE SURROGATES CONTAINING ASPARAGINE-DERIVED TETRAHYDROPYRIMIDINONES

摘要

Dipeptide surrogates Fmoc-Xxx-(cyclo)Asn-OBu are prepared from asparagine, aromatic aldehydes, and Fmoc-protected amino acid chlorides. The tetrahydropyrimidinone structure exist in a preferred ring conformation, as observed in a single crystal X-ray analysis of one of the derived carboxylic acids. As with other molecules with similar substitution patterns, the six-membered ring is held in a boat conformation. These dipeptide building blocks are deprotected at the C-terminal and/or N-terminal positions by known protocols. In addition, they function as ready participants for solid phase peptide synthesis. Finally, the constrained asparagine residue can be transformed to the native amino acid within a polypeptide framework, allowing for the direct interchange of a restricted system of known conformation and configuration to the native state under mild conditions. These peptide surrogates containing (cyclo)Asn are useful therapy of mammalian disease conditions, particularly in therapy of brain disorders.