Muscarine-like compounds derived from a pyrolysis product of cellulose

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.