Influence of protecting groups on O- and C-glycosylation with neuraminyl and ulosonyl dibutylphosphates

Synthesis of 3-Deoxy-d-manno-oct-2-ulosonic Acid (KDO) and Pseudaminic Acid C-Glycosides

“…The high equatorial selectivities of the C–C bonding forming reactions of pseudaminic acid donor 11 (Table , entries 5 and 6) are noteworthy in comparison to those of the related donors 8 and 9 , which showed modest preferences (∼2:1) for the formation of the equatorial over the axial isomers . This equatorial selectivity of 11 over 8 and 9 in C -glycosylation is consistent with the trend showed in O -glycosylation by the same donors .…”

“…b Anomeric ratios were determined by integration of the 1 H NMR spectra of the crude reaction mixtures c The nucleophilicity parameter reported for the acetaldehyde TMS enol ether is the same as that for the corresponding TIPS enol ether 31 The Journal of Organic Chemistry The anomeric configuration of the various C-glycosides was assigned on the basis of the 3 J C1,H3ax heteronuclear coupling constant as previously described for KDO and sialic acid Cglycosides: the equatorial C-glycosides displayed 3 J C1,H3ax values of 8.0−8.4 Hz, while the axial anomers had 0−3.5 Hz. 19,21,23 These assignments were confirmed by ROESY measurements (see Supporting Information) with the axial isomers showing the correlation of H4 and H6 in the pyranose ring with the methylene protons of the new substituents.…”

“…The anomeric configuration of the various C -glycosides was assigned on the basis of the 3 J C1,H3ax heteronuclear coupling constant as previously described for KDO and sialic acid C -glycosides: the equatorial C -glycosides displayed 3 J C1,H3ax values of 8.0–8.4 Hz, while the axial anomers had 0–3.5 Hz. ,, These assignments were confirmed by ROESY measurements (see Supporting Information) with the axial isomers showing the correlation of H4 and H6 in the pyranose ring with the methylene protons of the new substituents.…”

“…The KDO dibutyl phosphate 10 was obtained from the thioglycoside 1 by treatment with dibutylphosphoric acid, NIS, and triflic acid in dichloromethane at 0 °C as a single (α) anomer following the method used earlier for the preparation of 7 – 9 from 4 – 6 , and initially applied for the formation of 7 from the phenylthioglycoside analogue of 6 by Wong and co-workers . The pseudaminic acid donor 2 was similarly converted to 11 in a 78% yield as a 1:3 α:β mixture of anomers.…”

“…As such, the selectivities of C -glycosylation reactions are usually interpreted in terms of competing diastereoselective transition states for attack on the two faces of a glycosyl oxocarbenium ion in the product forming step of an S N 1 reaction. − Earlier we demonstrated that potent C -nucleophiles such as allyltributylstannane and various silyl enol ethers were excellent nucleophiles for the selective formation of equatorial C -glycosides on the activation of the N -acetyloxazolidinone-protected neuraminic acid dibutylphosphate 7 (Figure ), derived from 6 , with TMSOTf at low temperatures in dichloromethane/acetonitrile mixtures . On the other hand, recently we showed that the neuraminic dibutylphosphates 8 and 9 , derived from 4 and 5 , exhibited poor selectivity upon coupling to allyltributylstananne, thereby demonstrating the importance of protecting groups on the selectivity in a series of donors all with the same gg conformation of the side chain. We now turn our attention to C -glycosylation by the reaction of C -nucleophiles with the dibutylphosphates 10 and 11 , derived from 1 and 2 , with a view to gauging the influence of side chain conformation on C -glycosylation.…”