title: Synthesis of fused bicyclic thioglycosides of N-acylated glucosamine as analogues of mycothiol.
abstract: The synthesis of a fused bicyclic thioglycoside analogue of mycothiol, (3R)-3-acetylamino-4-one-6,7-dihydro-(1',2'-dideoxy-beta-D-glucopyranoso)[2',1'-f]-1,5-thiazepane (5), is reported. Treatment of phthalimido-protected peracetylated glucosamine with N-acetyl-cysteine and boron trifluoride-etherate gave the beta-linked thioglycoside, which was deprotected and cyclized, using HOBt and EDCl to form the lactam and giving the target structure. This mycothiol mimic and its tri-O-acetate will be investigated as potential inhibitors of enzymes involved in the biosynthesis of mycothiol. The protected derivative also has the potential to be an alpha-selective N-cysteinyl glucosamine donor; however, initial glycosylation attempts failed due to the apparent stability of the fused bicyclic system.
authors.affiliation: Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, S-106 91 Stockholm, Sweden.
authors.forename: Rikard
authors.initials: R
authors.lastname: Slättegård
authors.forename: David W
authors.initials: DW
authors.lastname: Gammon
authors.forename: Stefan
authors.initials: S
authors.lastname: Oscarson
mesh_terms: D000117:Acetylglucosamine; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002236:Carbohydrate Conformation; D003545:Cysteine / Q000737:chemistry*; D005944:Glucosamine / Q000737:chemistry*; D006020:Glycopeptides / Q000737:chemistry*; D007294:Inositol / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D013865:Thioglycosides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D001643:Bridged Bicyclo Compounds; D006020:Glycopeptides; D013865:Thioglycosides; C089265:mycothiol; D007294:Inositol; D003545:Cysteine; D005944:Glucosamine; D000117:Acetylglucosamine