Tetrahydrofuran Calpha-tetrasubstituted amino acids: two consecutive beta-turns in a crystalline linear tripeptide.
The synthesis of tetrahydrofuran Calpha-tetrasubstituted amino acids (TAAs) and their effect on the conformation in small peptides are reported. The synthesis starts from the protein amino acid methionine, which is protected at the C and N terminus and converted into the corresponding sulfonium salt by alkylation. Simple base treatment in the presence of an aryl aldehyde leads to the formation of tetrahydrofuran tetrasubstituted Calpha-amino acids in a highly diastereoselective (trans/cis ratio up to 97:3) reaction with moderate to good yields (35-78%) depending on the aldehyde used. Palladium-catalyzed coupling reactions allow a subsequent further functionalization of the TAA. The R,S,S-TAA-Ala dipeptide amide adopts a beta-turn type I conformation, whereas its S,R,S isomer does not. The R,S,S-Gly-TAA-Ala tripeptide amide shows in the solid state and in solution a conformation of two consecutive beta-turn type III structures, stabilized by i+3-->i intramolecular hydrogen bonds.
Maity
Prantik
P
Institut für Organische Chemie, Universität Regensburg, D-93040 Regensburg, Germany.
Zabel
Manfred
M
König
Burkhard
B
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D003460:Crystallization; D005663:Furans / Q000737:chemistry*; D006860:Hydrogen Bonding; D008715:Methionine / Q000737:chemistry; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D013237:Stereoisomerism
D000596:Amino Acids; D005663:Furans; D009842:Oligopeptides; C018674:tetrahydrofuran; D008715:Methionine