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Synthesis, docking studies and acetylcholinesterase inhibition of open-chain carbohydrate amides
* 1, 2 , 1, 2, 3 , 4 , 2 , 3 , 3 , 1
1  Centro de Química Estrutural, Institute of Molecular Sciences, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal
2  Departamento de Química, Unidade I&D FibEnTech, Universidade da Beira Interior, Av. Marquês d’Ávila e Bolama, 6201-001 Covilhã, Portugal
3  Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, C/Prof. García González 1, 41012 Sevilla, Spain
4  Department of Medicinal Chemistry, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
Academic Editor: Alfredo Berzal-Herranz


Alzheimer's disease (AD) is the age–related most common cause of dementia among elderly people, and a severe neurodegenerative disorder characterized by progressive memory and cognition losses, leading to disability and inevitably to death, considered as an urgent public health problem. It is the third leading cause of death after cancer and heart diseases. According to an update in 2020 of the estimates given in the World Alzheimer Report 2015, there are over 50 million people worldwide living with dementia in 2020. This number will almost double every 20 years, reaching 152 million in 2050. AChE inhibitors are the main stay drugs for early disease stages.

In this work we report on the development of a synthetic route to yield open chain sugar amides from commercially available carbohydrates. The synthetic pathway starts with diacetone glucose (DAG), which is converted into perbenzyl d-glucono-1,4-lactone in six steps. Reaction with aromatic or aliphatic amines in dichloromethane under reflux (0.5 h to 2 h) afforded the corresponding amides in high yield (80 – 95%) (Scheme 1). Bis(amidation) of a diamine was also accessed by this procedure in 3 h but reaction product was isolated in very low yield (13%). Docking studies and evaluation of acetylcholinesterase inhibition were carried out and the results will be disclosed.

Keywords: Sugar amides; Synthesis; Acetylcholinesterase inhibitors; Docking studies; Alzheimer’s disease