Total Synthesis of Phellinus ribis Glycans with Immunostimulating Activities by an Orthogonal One-Pot Glycosylation Strategy

Abstract

A total synthesis of nonasaccharide repeating units and shorter sequences from Phellinus ribis glycans with strong immunostimulating activities was achieved by an orthogonal one-pot glycosylation strategy based on an N-phenyltrifluoroacetimidate glycosylation, a Yu glycosylation, and an ortho-(1-phenylvinyl)benzoate glycosylation. The issues inherent to thioglycosides-based orthogonal one-pot glycosylations, such as aglycone transfer, are eliminated by this one-pot glycosylation strategy, which streamlines the chemical synthesis of glycans.

Key words

Phellinus ribis - glycans - one-pot reaction - glycosylation - total synthesis - oligosaccharides

Publication History

Received: 17 August 2022

Accepted after revision: 27 October 2022

Accepted Manuscript online:
27 October 2022

Article published online:
23 November 2022

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• 26 Tetrasaccharide 3; Typical ProcedureA solution of 10 (162.0 mg, 0.077 mmol) in 1:1 MeOH–CH₂Cl₂ (2 mL) was adjusted to pH 12 by the addition of NaOMe, and the mixture was stirred overnight at rt. The mixture was then neutralized to pH 7 with 1 M aq HCl, filtered, and concentrated. The residue was purified by column chromatography [Sephadex LH 20, MeOH–CH₂Cl₂ (1:1)] to give an intermediate; yield: 116.0 mg (89%).A mixture of the intermediate (50.0 mg, 0.029 mmol) and 10% Pd/C (316.8 mg) in EtOAc (3 mL)–MeOH (7 mL)–H₂O (0.7 mL)–HOAc (0.07 mL) was stirred under H₂ at rt for 2 d, then filtered and concentrated in vacuo. The residue was purified over a Sephadex TM LH-20 column (H₂O) to give 3 as a white solid; yield: 18.6 mg (81%); [α]_D ²⁵ –18.93 (c 0.120, H₂O).¹H NMR (400 MHz, D₂O): δ = 4.72 (d, J = 8.0 Hz, 1 H), 4.51 (dd, J = 8.0, 6.4 Hz, 2 H), 4.45 (d, J = 8.0 Hz, 1 H), 4.23–4.16 (m, 2 H), 3.94–3.80 (m, 5 H), 3.76–3.57 (m, 6 H), 3.53–3.22 (m, 13 H), 3.00 (t, J = 7.5 Hz, 2 H), 1.71–1.62 (m, 4 H), 1.47–1.39 (m, 2 H). ¹³C NMR (151 MHz, D₂O): δ = 102.88, 102.78, 102.57, 102.16, 84.31, 75.96, 75.66, 75.52, 75.47, 74.85, 74.81, 73.40, 73.01, 72.96, 72.80, 70.14, 69.51, 69.38, 69.26, 68.73, 68.54, 68.07, 60.63, 60.59, 39.32, 28.14, 26.43, 25.08, 22.05. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₉H₅₄NO₂₁: 752.3183; found: 752.3191.Hexasaccharide 2Prepared from 7, and purified over a Sephadex LH-20 column (H₂O) as a white solid; yield: 35 mg (86%); [α]_D ²⁵ –28.68 (c 0.08, H₂O). ¹H NMR (400 MHz, D₂O): δ = 4.73 (d, J = 8.0 Hz, 1 H), 4.55–4.48 (m, 4 H), 4.45 (d, J = 8.0 Hz, 1 H), 4.24–4.16 (m, 4 H), 3.94–3.81 (m, 7 H), 3.77–3.56 (m, 9 H), 3.53–3.43 (m, 9 H), 3.43–3.21 (m, 9 H), 2.99 (t, J = 7.5 Hz, 2 H), 1.72–1.60 (m, 4 H), 1.49–1.40 (m, 2 H). ¹³C NMR (201 MHz, D₂O): δ = 103.05, 102.88, 102.86, 102.81, 102.69, 102.19, 84.20, 75.98, 75.89, 75.70, 75.64, 75.56, 75.54, 75.50, 74.91, 74.87, 74.81, 74.57, 73.44, 73.06, 73.05, 73.03, 73.00, 72.83, 70.17, 69.60, 69.55, 69.44, 69.38, 69.37, 68.80, 68.74, 68.57, 68.52, 67.97, 60.69, 39.37, 28.18, 26.50, 23.24, 22.09, 20.07. HRMS (ESI): m/z [M + H]⁺ calcd for C₄₁H₇₄NO₃₁: 1076.4239; found: 1076.4240.Nonasaccharide 1Prepared from 21, and purified over a Sephadex LH-20 column (H₂O) as a white solid; yield: 29 mg (75%); [α]_D ²⁵ –43.78 (c 0.08, H₂O). ¹H NMR (400 MHz, D₂O): δ = 4.64 (d, J = 8.0 Hz, 1 H), 4.44–4.37 (m, 7 H), 4.35 (d, J = 8.0 Hz, 1 H), 4.13–4.08 (m, 5 H), 3.88–3.66 (m, 13 H), 3.63–3.45 (m, 16 H), 3.41–3.10 (m, 22 H), 2.89 (t, J = 7.5 Hz, 2 H), 1.62–1.50 (m, 4 H), 1.39–1.29 (m, 2 H). ¹³C NMR (201 MHz, D₂O): δ = 106.29, 106.27, 106.18, 106.10, 105.99, 105.82, 105.64, 105.49, 87.49, 81.81, 81.65, 79.28, 79.24, 78.99, 78.86, 78.83, 78.80, 78.73, 78.20, 78.19, 78.17, 78.11, 78.08, 78.03, 77.85, 77.46, 77.32, 76.73, 76.40, 76.34, 76.31, 76.29, 76.19, 76.12, 73.45, 72.85, 72.73, 72.71, 72.69, 72.67, 72.04, 71.93, 71.26, 71.11, 63.99, 63.83, 63.23, 63.15, 42.64, 31.47, 29.72, 28.28, 25.38. HRMS (ESI): m/z [M + H]⁺ calcd for C₅₉H₁₀₄NO₄₆: 1562.5824; found: 1562.5826.