Model studies toward the synthesis of dihydropyrimidinyl and pyridyl alpha-amino acids via three-component Biginelli and Hantzsch cyclocondensations.
A novel and versatile strategy for the synthesis of heterocyclic alpha-amino acids has been described. The use of components (aldehyde or beta-ketoester) bearing a masked glycinyl moiety in Biginelli and Hantzsch cyclocondensations allowed access to the 4-dihydropyrimidinyl-alpha-glycines, 4-dihydropyrimidinyl-alpha-alanines, 4-pyridyl-alpha-alanines, and 2-pyridyl-alpha-alanines classes. Dihydropyrimidinyl-amino acids were obtained as a mixture of diastereoisomers due to the formation of the stereocenter at C4 of the dihydropyrimidinone ring. Individual stereoisomers were isolated as pure compounds and their structures were assigned with the aid of X-ray crystallography and chiroptical properties. The enantiomeric purity of a representative selection of the above amino acids was greater than 96% as verified by derivatization to the corresponding Mosher's amides and subsequent (1)H and (19)F NMR spectroscopy. Incorporation of the 4-pyridyl-alpha-alanine derivative into a peptide chain is also described.
Dondoni
Alessandro
A
Dipartimento di Chimica, Università di Ferrara, Via L Borsari 46, 44100 Ferrara, Italy. adn@dns.unife.it
Massi
Alessandro
A
Minghini
Erik
E
Sabbatini
Simona
S
Bertolasi
Valerio
V
D024361:Amino Acids, Basic / Q000138:chemical synthesis*; D018360:Crystallography, X-Ray; D003500:Cyclization; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D010455:Peptides / Q000138:chemical synthesis; D011725:Pyridines / Q000138:chemical synthesis*; D011743:Pyrimidines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D024361:Amino Acids, Basic; D007202:Indicators and Reagents; D010455:Peptides; D011725:Pyridines; D011743:Pyrimidines