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.
Synthesis of N-Alkylated-L-Iminosugars and their Therapeutic Application in Cystic Fibrosis Lung Disease / Guaragna, Annalisa; DE FENZA, Maria; Esposito, Anna; Maria Cristina Dechecchi, ; Silvia, Munari; Giuseppe, Lippi; Giulio, Cabrini; Massimo, Aureli; Nicoletta, Loberto; Domitilla, Schiumarini; Alessandro, Sonnino; D'Alonzo, Daniele. - (2018). (Intervento presentato al convegno XXXVIII Convegno Nazionale della Divisione di Chimica Organica della Società Chimica Italiana tenutosi a Milano, Italy nel 9-13 Settembre 2018).
Synthesis of N-Alkylated-L-Iminosugars and their Therapeutic Application in Cystic Fibrosis Lung Disease
Annalisa Guaragna
;Maria De Fenza;Esposito, Anna;Daniele D’Alonzo
2018
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
