Large scale synthesis and regioselective protection schemes of ethyl 2-azido-2-deoxy-1-thio-α-d-cellobioside for preparation of heparin thiodisaccharide building blocks.
Crystalline acetylated ethyl 2-azido-2-deoxy-1-thio-α-d-cellobioside has been prepared on a multigram scale from cellobiose in an overall yield of 23% with no chromatography required and converted after deacetylation into the 4',6'-O-benzylidene and 4',6'-O-benzylidene-6-O-TBDMS protected derivatives. Applying a number of regioselective benzylation methods on these gave access to a variety of regioselectively protected derivatives, both mono-ols (2'- and 3-OH), diols (2',6-, 2',3-, and 3,6-di-OH), and triols (2',3,6- and 2',3',3-tri-OH). A number of these derivatives were further processed by benzoylation followed by removal or opening of the benzylidene acetal and selective oxidation of the exposed primary alcohol to give heparin building block intermediates comprising a range of possible sulfation patterns.
School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland.
Kevin
K
Sheerin
School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland.
Lorenzo
L
Guazzelli
School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland. Electronic address: stefan.oscarson@ucd.ie.
Stefan
S
Oscarson
D001386:Azides / Q000737:chemistry; D001593:Benzyl Compounds / Q000737:chemistry; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002475:Cellobiose / Q000737:chemistry*; D004187:Disaccharides / Q000737:chemistry*; D006493:Heparin / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D006497:Heparan Sulfate / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D009574:Nitro Compounds / Q000737:chemistry; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D001386:Azides; D001593:Benzyl Compounds; D002475:Cellobiose; D004187:Disaccharides; D006493:Heparin; D006497:Heparan Sulfate; D009574:Nitro Compounds; D013438:Sulfhydryl Compounds
Azidonitration; Heparan sulfate; Heparin; Phase transfer benzylation; Regioselective benzylation