Regioselective Deacetylation and Glycosylation in the Synthesis of the Sialyl Lewis X Tetrasaccharide, a Key Component of the Recognition Site of PSGL-1

Abstract

A high-yielding regioselective deprotection of three out of five hydroxy groups of a Lewis X trisaccharide, which proceeds under very mild basic conditions, and a regio- and stereoselective sialylation reaction enable an efficient access to the sialyl Lewis X tetrasaccharide.

Key words

glycosylation - regioselective deacetylation - solid-phase synthesis - glycopeptides - sialyl Lewis X

References and Notes

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17

Typical Procedure for Regioselective O-Deacetylation of the Trisaccharide 12: Trisaccharide 12 (2.11 g, 1.69 mmol) was dissolved in MeOH (150 mL) and freshly prepared NaOMe solution in MeOH was added carefully until pH 7.5 was obtained. Reaction was performed at r.t. and monitored by TLC every 30 min. After completion of the reaction (4 h 40 min), the mixture was neutralized with Amberlyst 15 to pH 6-6.5. The resin was removed by filtration, washed with MeOH, and the filtrate was concentrated under vacuum to give the crude 13 (1.78 g, 94% yield) as a white amorphous material. Trisaccharide 13 can be additionally purified on silica gel with EtOAc as eluent (R _f 0.35 in EtOAc). Spectroscopic data for 13: [α]_24D -26.6 (c = 2.00, MeOH). ^¹H NMR (COSY, CD₃OD): δ = 7.66-7.72 (4 H, m, H_ar), 7.19-7.39 (21 H, m, H_ar), 5.30-5.34 (2 H, m, H1-Fuc {5.33}, H3-Fuc {5.32}), 5.22 (1 H, d, H4-Fuc, J _3,4 = 2.6 Hz), 5.04-5.06 (1 H, m, H5-Fuc), 4.29-4.80 (8 H, m, CH₂Bn-2a {4.78}, CH₂-Bn-1a {4.66}, H1-GlcNAc {4.60}, CH₂Bn-1b {4.58}, CH₂Bn-2b {4.45}, CH₂Bn-3a {4.44}, H1-Gal {4.42}, CH₂Bn-3b {4.30}), 4.06 (1 H, t*, H4-GlcNAc, J _3,4 ≅ J _4,5 ≅ 9.3 Hz), 3.92-3.96 (1 H, m, H3-GlcNAc), 3.77-3.86 (5 H, m, H6a,b-Gal {3.85}, H6a-GlcNAc {3.84}, H2-Fuc {3.82}, H4-Gal {3.78}), 3.40-3.47 (3 H, m, H2-Gal {3.46}, H5-Gal {3.43}, H6b-GlcNAc {3.42}), 3.30-3.35 (2 H, m, H3-Gal {3.33}, H2-GlcNAc {3.31}), 3.07-3.10 (1 H, m, H5-GlcNAc), 2.03, 1.94, 1.80 (9 H, 3 × s, MeAc), 1.05 (9 H, s, Me-t-Bu), 1.04 [3 H, d, Me(6)-Fuc, J _5,6 = 6.5 Hz]. ^¹³C NMR (BB, HSQC, 100.6 MHz, CD₃OD): δ = 173.18, 172.48, 171.56 (C=O), 140.18, 139.78 (C _ipso -Ar), 137.17, 137.09 (C _{o , m , p} -Ar), 134.78, 134.18, 130.97 (C _ipso -Ar), 130.79, 129.35, 129.18, 129.06, 128.71, 128.65, 128.49, 128.43 (C _{o , m , p} -Ar), 103.41 (C1-Gal), 98.04 (C1-Fuc), 97.77 (C1-GlcNAc), 76.68 (C5-GlcNAc), 75.45 (C3-GlcNAc), 75.05 (C5-Gal), 75.02 (C2-Fuc), 74.82 (C3-Gal), 74.75 (C4-GlcNAc), 74.44 (CH₂Bn-1), 74.29 (CH₂Bn-3), 73.56 (C4-Fuc), 73.39 (CH₂Bn-2), 72.86 (C2-Gal), 71.25 (C3-Fuc), 70.34 (C6-Gal), 69.77 (C4-Gal), 68.87 (C6-GlcNAc), 65.53 (C5-Fuc), 48.80 (C2-GlcNAc), 27.41 (Me-t-Bu), 23.69, 20.99, 19.98 (MeAc), 16.33 [Me(6)-Fuc]. MS (ESI): m/z
[M + Na]⁺ calcd for C₆₁H₇₅NO₁₇SiNa: 1144.47; found: 1144.48. HRMS (ESI-TOF): m/z [M + Na]⁺ calcd for C₆₁H₇₅NO₁₇SiNa: 1144.4702; found: 1144.4690.