Concise total synthesis of glucosepane

Glucosepane is a structurally complex protein posttranslational modification that is believed to exist in all living organisms. Research in humans suggests that glucosepane plays a critical role in the pathophysiology of both diabetes and human aging, yet comprehensive biological investigations of t...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2015-10, Vol.350 (6258), p.294-298
Main Authors: Draghici, Cristian, Wang, Tina, Spiegel, David A.
Format: Article
Language:English
Subjects:
Amino acids
Amino Acids - chemistry
Biochemistry
Chemistry
Crosslinking
Diabetes
Glucose
Glucose - chemistry
Glycation End Products, Advanced - chemical synthesis
Humans
Imidazoles - chemical synthesis
Literary Devices
Lysine
Metabolites
Organic Chemistry
Protein Processing, Post-Translational
Proteins
Proteins - chemistry
Proteins - metabolism
Synthesis
Tautomers
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Summary:Glucosepane is a structurally complex protein posttranslational modification that is believed to exist in all living organisms. Research in humans suggests that glucosepane plays a critical role in the pathophysiology of both diabetes and human aging, yet comprehensive biological investigations of this metabolite have been hindered by a scarcity of chemically homogeneous material available for study. Here we report the total synthesis of glucosepane, enabled by the development of a one-pot method for preparation of the nonaromatic 4H-imidazole tautomer in the core. Our synthesis is concise (eight steps starting from commercial materials), convergent, high-yielding (12% overall), and enantioselective. We expect that these results will prove useful in the art and practice of heterocyclic chemistry and beneficial for the study of glucosepane and its role in human health and disease.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aac9655