De novo synthesis of uronic acid building blocks for assembly of heparin oligosaccharides.
An efficient de novo synthesis of uronic acid building blocks is described. The synthetic strategy relies on the stereoselective elongation of thioacetal protected dialdehydes 12 a and 17. The dialdehydes are prepared from D-xylose, a cheap and commercially available source. A highly stereoselective MgBr(2)OEt(2)-mediated Mukaiyama aldol addition to C4-aldehyde 12 a is performed to obtain D-glucuronic acid building block 16, whereas L-iduronic acid building block 22 is prepared by MgBr(2)OEt(2)-mediated cyanation of C5-aldehyde 17. Synthesis of a heparin disaccharide demonstrates the utility of the de novo strategy for the assembly of glycosaminoglycan oligosaccharides.
Adibekian
Alexander
A
Laboratory for Organic Chemistry, Swiss Federal Institute of Technology ETH Zürich, Wolfgang-Pauli-Strasse 10, HCI F312, 8093 Zürich, Switzerland.
Bindschädler
Pascal
P
Timmer
Mattie S M
MS
Noti
Christian
C
Schützenmeister
Nina
N
Seeberger
Peter H
PH
D018360:Crystallography, X-Ray; D006493:Heparin / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D014574:Uronic Acids / Q000138:chemical synthesis* / Q000737:chemistry*
D009844:Oligosaccharides; D014574:Uronic Acids; D006493:Heparin