Amino acid derived heterocycles: lewis acid catalyzed and radical cyclizations from peptide acetals.
Bicyclization of peptide acetals via nucleophilic attack of a phenyl group on an endocyclic acyliminium ion 4 was explored as a route to novel amino acid derived heterocycles and peptidomimetic scaffolds. In the presence of protic acid, bridged structures such as 6 are formed readily from phenylalanine derivatives, but the fused-ring analogues 5 could not be obtained in good yield. In contrast, radical cyclization of the bromophenyl dihydropyrazinone 7 provides an effective alternative for the synthesis of 5 (n = 0, 1, 2). Additional versatility in this process was demonstrated by efficient synthesis of a different fused ring system, represented by the antihelmintic praziquantel, 8.
Todd
Matthew H
MH
Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley 94720-1460, USA.
Ndubaku
Chudi
C
Bartlett
Paul A
PA
D000080:Acetals; D000596:Amino Acids / Q000737:chemistry*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D008968:Molecular Conformation; D018716:Molecular Mimicry; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D004364:Pharmaceutical Preparations; D011223:Praziquantel / Q000138:chemical synthesis; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry
D000080:Acetals; D000596:Amino Acids; D010455:Peptides; D004364:Pharmaceutical Preparations; D011719:Pyrazines; D011223:Praziquantel