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.
The key step in the first chemical synthesis of anthrose (16) and its methyl alpha- (6) and beta-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-alpha-D-mannopyranoside (1). To prepare methyl alpha-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 alpha-glycoside 6. Synthesis of methyl beta-anthroside (22) comprised the same sequence of reactions, starting from the known methyl 4-azido-3-O-benzyl-4,6-dideoxy-beta-D-mannopyranoside (17), which was prepared from 1. In the synthesis of anthrose (16), 1-thio-beta-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.
Saksena
Rina
R
NIDDK, LMC, National Institutes of Health, Bethesda, MD 20892-0815, USA.
Adamo
Roberto
R
Kovác
Pavol
P
D000606:Amino Sugars / Q000138:chemical synthesis / Q000737:chemistry*; D022122:Anthrax Vaccines / Q000138:chemical synthesis / Q000737:chemistry*; D002240:Carbohydrate Sequence; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D005960:Glucosides / Q000138:chemical synthesis / Q000737:chemistry*; D008969:Molecular Sequence Data; D018074:Vaccines, Conjugate / Q000737:chemistry
C504007:4,6-dideoxy-4-(3-hydroxy-3-methylbutanamido)-2-O-methylglucopyranose; D000606:Amino Sugars; D022122:Anthrax Vaccines; D005960:Glucosides; D018074:Vaccines, Conjugate; C504008:methyl 4,6-dideoxy-4-(3-hydroxy-3-methylbutanamido)-2-O-methylglucopyranose; D003847:Deoxyglucose