title: Concise total synthesis of glucosepane.
abstract: 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.
authors.affiliation: Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520, USA.
authors.forename: Cristian
authors.initials: C
authors.lastname: Draghici
authors.affiliation: Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520, USA. Department of Pharmacology, Yale University, 333 Cedar Street, New Haven, CT 06520, USA. david.spiegel@yale.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Spiegel
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D005947:Glucose / Q000737:chemistry; D017127:Glycation End Products, Advanced / Q000138:chemical synthesis*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D000596:Amino Acids; D017127:Glycation End Products, Advanced; D007093:Imidazoles; D011506:Proteins; C543060:glucosepane; C029899:imidazole; D005947:Glucose