The doctoral dissertations of the former Helsinki University of Technology (TKK) and Aalto University Schools of Technology (CHEM, ELEC, ENG, SCI) published in electronic format are available in the electronic publications archive of Aalto University - Aaltodoc.
Aalto

Towards the Synthesis of the Disaccharide Fragment of Pradimicin

Tatja Maunula

Dissertation for the degree of Doctor of Philosophy to be presented with due permission of the Department of Chemical Technology for public examination and debate in Auditorium KE 2 (Komppa Auditorium) at Helsinki University of Technology (Espoo, Finland) on the 18th of June, 2004, at 12 o'clock noon.

Dissertation in PDF format (ISBN 951-22-7038-2)   [902 KB]
Dissertation is also available in print (ISBN 951-22-7037-4)

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.

Keywords: amino sugars, antibiotics, antifungal, asymmetric synthesis, glycosyl fluoride

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© 2004 Helsinki University of Technology

Last update 2011-05-26