Synthesis of N-Alkylated-L-Iminosugars and their Therapeutic Application in Cystic Fibrosis Lung Disease

A de novo stereoselective approach for the preparation of unnatural L-DNJ, and its alkylated derivatives, has been devised starting from a heterocyclic homologating system and Garner aldehyde. Furthermore, a new eco-friendly and convenient synthetic path has been performed to prepare the alkyl chains and the corresponding N-alkyl DNJ derivatives, by the use of the well-known PPh3 polymer bound/I2 system. Early in vitro assays on CF bronchial epithelial cells using iminosugars in enantiomerically pure forms (NBDNJ and NNDNJ) demonstrated that both D- and L-iminosugars were able to reduce the P. aeruginosa stimulated IL-8 mRNA expression at nanomolar concentration.