A simplified synthesis of α-d-galactopyranose 1,3,4,6-tetraacetate

Chemical Synthesis of the Galacturonic Acid Containing Pentasaccharide Antigen of the O-Specific Polysaccharide of Vibrio cholerae O139 and Its Five Fragments

“…Its preparation required an orthogonally protected, β-directing galactosyl donor with a selectively removable protecting group at O-2. Such a donor, 14, 21 was readily obtained (77% for two steps) by levulinylation at O-2 of the known α-D-galactopyranose 1,3,4,6-tetraacetate 26 33 followed by conventional treatment 34 of the formed, fully protected substance 27 with HBr in HOAc (Scheme 2).…”

“…LevOH (7.10 mL, 8.05 g, 69.32 mmol) was added to a solution of monosaccharide 26 (20.00 g, 57.45 mmol), EDCI (13.20 g, 68.85 mol), and DMAP (0.70 g, 5.73 mmol) in DCM (100 mL). The reaction was stirred at room temperature overnight.…”

“…After addition of DCM (200 mL), the precipitate that formed (AgI) was filtered off, and the filtrate was washed with a 1:1 mixture of saturated aqueous solutions of Na 2 S 2 O 3 and NaHCO 3 ). The aqueous layer was backwashed with DCM (3 × 100 mL), the combined DCM solutions were dried and concentrated, and chromatography (40 g of silica, 14% acetone in toluene) yielded trisaccharide 32 (4.48 g, 3.17 mmol, 79%) and acceptor 13 (0.16 g, 0.25 mmol, 6%): R f 0.32 (toluene/acetone 6:1); II = 5.9 Hz, H-5 II ), 3.37 (ddd, 1H, H-2 II ), 3.29 (t, 2H, J = 5.3 Hz, CH 2 (linker)), 2.94 (ddd, 1H, J = 3.4, 10.0, 18.7 Hz, CH 2 (Lev)), 2.80 (ddd, 1H, J = 3.4, 10.0, 17.4 Hz, CH 2 (Lev)), 2.63 (ddd, 1H, J = 3.5, 6.4, 18.7 Hz, CH 2 (Lev)), 2.36 (ddd, 1H, J = 3.5, 6.4, 17.4 Hz, CH 2 (Lev)), 2.18, 2.12, 2.05, 1.99 (CH 3 (Lev), 3 × CH 3 (Ac)), 0.85 (S, 9H, C(CH 3 ) 3 ), 0.00 (s, 6H, 2 × CH 3 ); 13 (33). Trisaccharide 32 (20.0 mg, 0.014 mmol) was acetylated with pyridine (0.2 mL) and Ac 2 O (0.1 mL) conventionally.…”

Synthesis of carbohydrate building blocksviaregioselective uniform protection/deprotection strategies

“…A few years later, Chittenden reported a simplified method for the synthesis of 1,3,4,6-tetra- O -acetyl-α-D-galactopyranose using trifluoroacetic acid-water solution. 88 1,2,3,4,6-penta- O -acetyl-β-D-galactopyranose 48 was treated with aqueous trifluoroacetic acid at rt for 5 h to give 1,3,4,6-tetra- O -acetyl-α-D-galactopyranose 49 in 72% yield (Scheme 10). The α-anomer of D-galactopyranose/glucopyranose pentaacetate is unreactive under these reaction conditions.…”

Glycosyl nitrates in synthesis: streamlined access to glucopyranose building blocks differentiated at C-2

“…It requires strict control of the reaction temperature and reactant addition order, but still provides a low yield of 27%. 26 Somewhat more straightforward procedures have been developed for the synthesis of 2-OH galactose 27 and mannose 28 derivatives, but these approaches do not work for the synthesis of 2-OH glucose 2 . Our reinvestigation of the synthesis of 2-OH glucose led to the discovery of a scalable one-step protocol with cerium(IV) ammonium nitrate (CAN).…”