Towards the synthesis of the disaccharide fragment of pradimicin
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Doctoral thesis (monograph)
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Date
2004-06-18
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Language
en
Pages
145
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Report / Helsinki University of Technology, Department of Chemistry, Laboratory of Organic Chemistry, 1/2004
Abstract
Pradimicin is a novel antibiotic consisting of a benzo[a]naphthacenequinone aglycon, an amino acid and a disaccharide fragment. In this study, the α-analogue of the disaccharide derivative of pradimicin A was synthesized in its protected form. The disaccharide moiety of pradimicin A was built up from a suitably protected, commercially available D-xylose derivative and the amino sugar part, synthesized from L-threonine. The synthesis of the target amino sugar started with the conversion of the L-threonine derived aldehyde to the desired E-enoate via a modified Horner-Wadsworth-Emmons olefination. Ruthenium-catalyzed cis-dihydroxylation of the double bond produced a mixture of anti- and syn-aminodiols, of which the former was lactonized under acidic conditions. Platinum-catalyzed reduction of the lactone produced a mixture of lactols, which upon treatment with DAST provided a mixture of α- and β-fluorinated amino sugar derivatives. Both the α- and β-fluorides were transformed to suitable glycosyl fluorides of pradimicin A via successive N-methylation by MeI/Ag2O, deacetylation and regioselective benzoyl protection at the C2-position. Final coupling of the α-glycosyl fluoride with the D-xylose derived thioglycoside donor by NBS furnished the protected α-analogue of the disaccharide fragment of pradimicin A.Description
Keywords
amino sugars, antibiotics, antifungal, asymmetric synthesis, glycosyl fluoride
