Diversity-oriented synthesis and preliminary biological screening of highly substituted five-membered lactones and lactams originating from an allyboration of aldehydes and imines.
alpha-exo-Methylene-gamma-lactones and alpha-exo-methylene-gamma-lactams are key structural units in a wide variety of natural products. These substances exhibit a high degree of bioactivity against numerous biological targets that play important roles in several diseases. A library of functionalized gamma-lactones and gamma-lactams containing both unsaturated and saturated side chains at the alpha position of the ring was synthesized. The generation of this library first involves sequential allylation of aldehydes or imines with 2-alkoxycarbonyl allylboronates, followed by ring closure to give alpha-exo-methylene-gamma-lactones or alpha-exo-methylene-gamma-lactams, which are subjected to various transition metal catalyzed coupling reactions to introduce additional diversity. A subset of the library was screened for inhibition of homoserine transacetylase (HTA) from Haemophilus influenzae and showed promising initial activity profiles.
Elford
Tim G
TG
Department of Chemistry, University of Alberta, Alberta, Canada.
Ulaczyk-Lesanko
Agnieszka
A
De Pascale
Gianfranco
G
Wright
Gerard D
GD
Hall
Dennis G
DG
D000123:Acetyltransferases / Q000037:antagonists & inhibitors; D000447:Aldehydes / Q000737:chemistry; D000998:Antiviral Agents / Q000138:chemical synthesis*; D001897:Boronic Acids; D004353:Drug Evaluation, Preclinical; D006193:Haemophilus influenzae / Q000201:enzymology; D007097:Imines / Q000737:chemistry; D007769:Lactams / Q000138:chemical synthesis* / Q000494:pharmacology; D007783:Lactones / Q000138:chemical synthesis* / Q000494:pharmacology
D000447:Aldehydes; D000998:Antiviral Agents; D001897:Boronic Acids; D007097:Imines; D007769:Lactams; D007783:Lactones; D000123:Acetyltransferases; C021369:homoserine O-acetyltransferase