Efficient synthesis of 4-amino-4-deoxy-L-arabinose and spacer-equipped 4-amino-4-deoxy-L-arabinopyranosides by transglycosylation reactions

Abstract

Methyl 4-azido-4-deoxy-l-arabinopyranoside has been synthesized in five steps starting from methyl-d-xylopyranoside in a multigram scale without chromatographic purification in 78% overall yield. The transformation relied on selective tosylation/nosylation at O-4 followed by acylation, SN2 displacement with sodium azide, and subsequent deprotection. The methyl 4-azido-4-deoxy-arabinoside was then converted into allyl, propenyl,-bromohexyl, and chloroethoxyethyl spacer glycosides by transglycosylation with the respective alcohols in good yields and fair anomeric selectivity. Reduction of the azido group and further transformations of the aglycone afforded-thiol- containing spacer derivatives. Coupling to maleimide-activated BSA provided a potent immunogen, which was used to generate murine and rabbit polyclonal sera binding to LPS-core epitopes containing 4-amino-4-deoxy-arabinose residues. © Georg Thieme Verlag Stuttgart - New York.