Sang-Hyeup Lee

The preparation of polymer bound β-ketoesters and their conversion into an array of oxazoles

A series of diverse polymer bound β-ketoesters have been prepared using a transesterification reaction between t-butyl β-ketoesters and a hydroxybutyl functionalized JandaJel resin. Additionally, these highly useful polymer bound substrates have also been prepared using a transesterification reaction with commercially available methyl or ethyl β-ketoesters using lithium perchlorate as a catalyst. The polymer bound β-ketoesters were then converted into the corresponding α-diazo-β-ketoesters using standard diazo transfer conditions and these products were utilized in the synthesis of an array of oxazoles.

Discovering Additional Chemical and Biological Functions for 3-Oxo-N-Acylhomoserine Lactones

Introduction The term quorum sensing has been coined to describe the ability of a population of unicellular bacteria to act as a multicellular organism in a cell-density-dependent manner, that is, a way to sense “how many are out there” [1]. Bacteria use small diffusible molecules to exchange information amongst themselves. An important class of autoinducers is the family of N-acylhomoserine lactones (AHLs) used by Gram negative bacteria. Variation in N-acyl chain length and oxidation state of AHLs provide for bacterial strain specificity in the signaling process and subsequent synchronization of gene expression. Upon reaching a critical threshold concentration, they bind to their cognate receptor proteins, triggering the expression of target genes. Pseudomonas aeruginosa is a common environmental microorganism that has acquired the ability to take advantage of weaknesses in the host immune system to become an opportunistic pathogen in humans [2]. Over the last ten years, significant progress has been made in elucidating the molecular mechanisms underlying P. aeruginosa pathogenicity. Two different AHLs, N-(3-oxododecanoyl) homoserine lactone 1 and N-butyrylhomoserine lactone, have been identified as the main quorum sensing signaling molecules in P. aeruginosa [3]. Importantly, genes regulated by this mechanism control the expression of virulence factors as well as the formation of structures known as biofilms [4]. Recently, we have assigned new roles for these compounds through the demonstration that 1 performs a previously unrecognized role; the autoinducer itself and a corresponding degradation product derived from an unusual Claisen-like condensation reaction function as innate bactericidal agents [5].