title: Muscarine-like compounds derived from a pyrolysis product of cellulose.
abstract: Cellulose represents a key component of a renewable biomass source, from which chiral compounds with a high added value in the application for the synthesis of potentially bioactive molecules can be obtained. The anhydrosugar (1R,5S)-1-hydroxy-3,6-dioxa-bicyclo[3.2.1]octan-2-one (LAC), produced on the gram-scale by catalytic pyrolysis of cellulose, was used as a building block in the synthesis of five new enantiomerically pure muscarine-like products. The structures of the target compounds 4-8 showed different substituents at the C-2 and C-4 positions, but each of them had the same (2S,4R) configuration as the natural (+)-muscarine. A renewed interest in new muscarinic analogues is due to the design and synthesis of molecules exhibiting a higher selectivity for a specific muscarinic receptor and due to the development of effective agents in the treatment of Alzheimer's disease and other cognitive disorders. In this context, products 4-8 were investigated with respect to their binding affinity to human M1-M5 muscarinic acetylcholine receptors. The data indicated that compound 8, emerging as the most active in the series with values comparable to natural (+)-muscarine and a moderate selectivity in favor of the hM2 subtype receptor, also exhibited the highest stability during the interaction with the hM2 (3UON) subtype muscarinic receptor by using a docking calculation.
authors.affiliation: Università degli studi di Trento, Dipartimento di Fisica, Laboratorio di Chimica Bioorganica, via Sommarive 14, 38123 Povo, Trento, Italy. ines.mancini@unitn.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Defant
authors.forename: Ines
authors.initials: I
authors.lastname: Mancini
authors.forename: Rosanna
authors.initials: R
authors.lastname: Matucci
authors.forename: Cristina
authors.initials: C
authors.lastname: Bellucci
authors.forename: Federico
authors.initials: F
authors.lastname: Dosi
authors.forename: Danilo
authors.initials: D
authors.lastname: Malferrari
authors.forename: Daniele
authors.initials: D
authors.lastname: Fabbri
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D002482:Cellulose / Q000737:chemistry*; D015394:Molecular Structure; D009116:Muscarine / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D009116:Muscarine; D002482:Cellulose