Metal-catalyzed derivatization of C(alpha)-tetrasubstituted amino acids and their use in the synthesis of cyclic peptides.
C(alpha)-tetrasubstituted amino acids are important building blocks in the design and preparation of novel peptidomimetics. We report on the functionalization of the C(alpha)-tetrasubstituted THF amino acid rac-5 by copper(I) catalyzed N-arylation reactions. The aryl bromide substituent of rac-5 is replaced by a variety of aliphatic and aromatic amines. Intramolecular N-arylation yielded only small amounts of a cyclic tripeptide 2, whereas cyclic tripeptide ethers 4 and 50 were obtained in an enantiomerically pure form from a palladium(0)-catalyzed intramolecular O-arylation.
Grauer
Andreas
A
Institut für Organische Chemie, Universität Regensburg, 93040 Regensburg, Germany.
Späth
Andreas
A
Ma
Dawei
D
König
Burkhard
B
D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry*; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003500:Cyclization; D010165:Palladium / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D011487:Protein Conformation
D000596:Amino Acids; D010456:Peptides, Cyclic; D010165:Palladium; D003300:Copper