Studies toward a conjugate vaccine for anthrax. Synthesis and characterization of anthrose [4,6-dideoxy-4-(3-hydroxy-3-methylbutanamido)-2- O-methyl- d-glucopyranose] and its methyl glycosides

• Published in: Carbohydrate research 2005-07, Vol.340 (9), p.1591-1600
• Main Authors: Saksena, Rina, Adamo, Roberto, Kováč, Pavol
• Format: Article
• Language: English
• Subjects: Amino Sugars - chemical synthesis; Amino Sugars - chemistry; Anthrax Vaccines - chemical synthesis; Anthrax Vaccines - chemistry; Carbohydrate Sequence; Deoxyglucose - analogs & derivatives; Deoxyglucose - chemical synthesis; Deoxyglucose - chemistry; Glucosides - chemical synthesis; Glucosides - chemistry; Methyl α-anthroside; Methyl β-anthroside; Molecular Sequence Data; Perosamine; Thioglycoside hydrolysis; Vaccines, Conjugate - chemistry
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/j.carres.2005.04.010

[Display omitted] The key step in the first chemical synthesis of anthrose ( 16) and its methyl α- ( 6) and β-glycoside ( 22) was inversion of configuration at C-2 in triflates 10, 2, and 18, respectively, obtained from the common intermediate, methyl 4-azido-3- O-benzyl-4,6-dideoxy-α- d-mannopyranoside ( 1). To prepare methyl α-anthroside ( 6), methylation at O-2 of the gluco product 3, obtained from 2, was followed by hydrogenation/hydrogenolysis of the formed 2-methyl ether 4, to simultaneously remove the protecting benzyl group and reduce the azido function. Subsequent N-acylation of the formed amine 5 with 3-hydroxy-3-methylbutyric acid gave the target methyl α-glycoside 6. Synthesis of methyl β-anthroside ( 22) comprised the same sequence of reactions, starting from the known methyl 4-azido-3- O-benzyl-4,6-dideoxy-β- d-mannopyranoside ( 17), which was prepared from 1. In the synthesis of anthrose ( 16), 1-thio-β-glucoside 11, obtained from 1 through 10, was methylated at O-2, and the azido function in the resulting benzylated 1-thioglycoside 12 was selectively reduced to give amine 13. After N-acylation with 3-hydroxy-3-methylbutyric acid, 1-thioglycoside 14 was hydrolyzed to give the corresponding reducing sugar, aldol 15, which was debenzylated to afford anthrose.