Titre : Design, Synthesis and Biomedical Applications of Azabicyclo[X.Y.0]alkanone Amino Acids
Endroit : Pavillon J.-Armand Bombardier, salle 1035 à 11 h 00.
Cette conférence sera prononcée par Monsieur Nagavenkata Durga Prasad Atmuri, étudiant au doctorat, du laboratoire de William Lubell, professeur au Département de chimie de l'Université de Montréal.
Résumé: Electrophilic transannular cyclization of 8-, 9-, and 10-membered macrocyclic dipeptide lactams has been shown to give effective entry to azabicyclo[X.Y.0]alkanone amino acid derivatives possessing 5,5-, 5,6-, 6,5-, 6,4-, 6,6-, and 7,5-fused ring systems. Our presentation describes this synthetic strategy starting from the preparation and coupling of vinyl-, allyl-, homoallyl- and homohomoallylglycine building blocks to prepare dipeptides that undergo ring-closing metathesis furnishing the macrocyclic lactams. Transannular iodolactamization gave typically azabicyclo[X.Y.0]alkanone possessing iodine on the lactam ring. X-ray crystallographic and spectroscopic analyses of the 8-, 9- , and 10-member macrocycles, as well as certain bicycle analogs demonstrate their potential to serve as constrained dipeptides that mimic the central residues of ideal β-turn geometry. Moreover, palladium catalyzed arylation of dehydro-indolizidin-2-one analogs has been developed and employed to prepare analogues of prostaglandin F2alpha receptor modulators for examination in myometrial contraction assays as potential agents for delaying preterm birth.
