Stereoselective Synthesis of 5-epi-α-Sialosides Related to the Pseudaminic Acid Glycosides. Reassessment of the Stereoselectivity of the 5-Azido-5-deacetamidosialyl Thioglycosides and Use of Triflate as Nucleophile in the Zbiral Deamination of Sialic Acids.
With a view to the eventual synthesis of glycosyl donors for the stereocontrolled synthesis of pseudaminic acid glycosides, the stereocontrolled synthesis of a d-glycero-d-gulo sialic acid adamantanylthioglycoside carrying an axial azide at the 5-position is described. The synthesis employs levulinic acid as nucleophile in the oxidative deamination of an N-acetylneuraminic acid thioglycoside leading to the formation of a 3-deoxy-d-glycero-d-galacto-2-nonulosonic acid (KDN) derivative selectively protected as 5-O-levulinate. Replacement of the levulinate by triflate enables introduction of the axial azide and hence formation of the glycosyl donor. A shorter synthesis uses trifluoromethanesulfonate as nucleophile in the oxidative deamination step when the 5-O-triflyl KDN derivative is obtained directly. Glycosylation reactions conducted with the 5-azido-d-glycero-d-gulo-configured sialyl adamantanylthioglycoside at -78 °C are selective for the formation of the equatorial glycosides, suggesting that the synthesis of equatorial pseudaminic acid glycosides will be possible as suitable donors become available. A comparable N-acetylneuraminic acid adamantanylthioglycoside carrying an equatorial azide at the 5-position was also found to be selective for equatorial glycoside formation under the same conditions, suggesting that reinvestigation of other azide-protected NeuAc donors is merited. Glycosylation stereoselectivity in the d-glycero-d-gulo series is discussed in terms of the side-chain conformation of the donor.
Department of Chemistry, Wayne State University , Detroit, Michigan 48202, United States.
Bibek
B
Dhakal
Department of Chemistry, Wayne State University , Detroit, Michigan 48202, United States.
Szymon
S
Buda
Department of Chemistry, Wayne State University , Detroit, Michigan 48202, United States.
David
D
Crich
D002240:Carbohydrate Sequence; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D003641:Deamination; D006027:Glycosides / Q000737:chemistry*; D006031:Glycosylation; D066244:Proton Magnetic Resonance Spectroscopy; D012794:Sialic Acids / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D013400:Sugar Acids / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry*
C513444:5,7-diacetamido-3,5,7,9-tetradeoxynonulosonic acid; D006027:Glycosides; D012794:Sialic Acids; D013400:Sugar Acids; D013438:Sulfhydryl Compounds