O-Alkylation at the anomeric centre for the stereoselective synthesis of Kdo-α-glycosides

A latent reactive handle for functionalising heparin-like and LMWH deca- and dodecasaccharides

“…( S )-2,3-Dibenzyloxy propanol was readily converted to its tosylate derivative 13 22 and subsequent alkylation of 1 with 13 did proceed, but only in low yield, as the reaction required heating, and as we had seen with other O4 alkylations, resulted in competing starting material degradation ( Scheme 5 ). To circumvent this, employing the corresponding triflate electrophile 14 23 enabled efficient alkylation of O4 for two d -GlcN derivatives β- 1 and 16 (differentially protected at O6) in good to excellent yields. The slightly lower yield for the formation of 18 was attributed to a competing transesterification reaction, evidenced by formation of a species with very similar R f to 18 as the reaction progressed.…”

“…NaH (60% in mineral oil) (248.0 mg, 6.2 mmol) was added in two portions over 30 min while being kept under N 2 . 14 23 (2.49 g, 6.2 mmol) in dry DMF (20 mL) was then added dropwise and the suspension allowed to warm to RT and stirred for a further 3 h. TLC analysis (3/1, hexane/EtOAc) showed the reaction to be complete and quenching was effected with aqueous NaHCO 3 (1 mL). The solution was partitioned between EtOAc and H 2 O.…”

“…while being kept under N 2 . 14 23 (1.81 g, 4.46 mmol) in dry THF (10 mL) was then added dropwise and the suspension allowed to warm to RT and stirred for a further 2 h. TLC analysis (3/1, hexane/EtOAc) showed the reaction to be virtually complete (Note: allowing the reaction continue for longer resulted in no further consumption of starting material and the formation of another product; suggested to be transesterification) and quenching was effected with glacial AcOH (4.1 mmol) and solvents removed in vacuo . The solution was partitioned between EtOAc and H 2 O.…”

Anomeric O-acylation of Kdo using alkyl and aryl isocyanates

“…Several groups have examined the a-selective glycosidation of Kdo to introduce a functional spacer, which can be potentially utilized for further coupling to other macromolecules. [1][2][3][4][5][6] Up to date, two groups have accomplished the synthesis of an a-Kdo derivative carrying a spacerarm in high yields. [5][6][7] However, these methods have not yet been fully developed as a general conjugation method for chemically synthesized OS containing Kdo at the reducing end.…”

Stereoselective Glycosylation of 3-Deoxy-d-manno-2-octulosonic Acid with Batch and Microfluidic Methods

“…With these Kdo donors, the undesirable b-side attack by a glycosyl acceptor is prevented by the presence of the bulky isopropylidene or TBS group. Other glycosylations have also been reported; with Kdo chloride, bromide, [8][9][10][11][12][13][14][15][16] phosphite, 17 and 3-phenylselenyl-Kdo 18 via substitution of 6-O-triflate of glucosamine with a Kdo residue 19 and that of 3-iodo intermediates with acyclic saccharide precursors. 20 However, many of these methods are difficult to apply for the synthesis of complex LPS partial structures with many acyl groups and phosphates.…”