A versatile annulation protocol toward novel constrained phosphinic peptidomimetics.
The development of a novel 3-center 2-component annulation reaction between alpha,omega-carbamoylaldehydes and suitably monoalkylated phosphinic acids is reported. Depending on the starting alpha,omega-carbamoylaldehyde, diverse phosphinic scaffolds varying in the size of their rigidity element, the nature and stereochemistry of substituents, and the participation of heteroatoms in the azacyclic ring system can be obtained in one synthetic step and in high yield. In addition, this methodology allows the synthesis of Fmoc-protected constrained aminophosphinic acids that can be easily converted to suitable pseudodipeptide building blocks compatible with the requirements of peptide synthesis on the solid phase. Finally, the careful choice of both substituents and protecting groups can provide functionally diverse, orthogonally protected constrained scaffolds for extended derivatization of the target phosphinic peptidomimetic structures.
Nasopoulou
Magdalini
M
Department of Chemistry, Laboratory of Organic Chemistry, University of Athens, Panepistimiopolis Zografou 15771, Athens, Greece.
Georgiadis
Dimitris
D
Matziari
Magdalini
M
Dive
Vincent
V
Yiotakis
Athanasios
A
D000447:Aldehydes / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D003500:Cyclization; D005449:Fluorenes / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D010721:Phosphinic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D010875:Pipecolic Acids / Q000138:chemical synthesis / Q000737:chemistry
D000447:Aldehydes; D000596:Amino Acids; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010455:Peptides; D010721:Phosphinic Acids; D010875:Pipecolic Acids