A Novel Glycosyl Donor with a Triisopropylsilyl Nonparticipating Group in Benzyl-Free Stereoselective 1,2-cis-Galactosylation

Abstract

A novel glycosyl donor with a triisopropylsilyl (TIPS) nonparticipating group at O-2 is introduced for use in 1,2-cis-galactosylation. Coupling the 2-O-TIPS-substituted thiogalactoside donor with a series of mono- and disaccharide glycosyl acceptors was found to lead exclusively to α-linked oligosaccharides. The observed exceptionally high α-selectivity was interpreted in terms of conformational changes in the glycosyl cation induced by the bulky 2-O-TIPS group.

Key words

glycosylation - stereoselectivity - stereoselective synthesis - conformation - protecting groups - triisopropylsilyl group - 4-(3-chloropropoxy)phenyl glycosides

• References and Notes

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• 43 Analytical data for 4-(3-Chloropropoxy)phenyl 2,3,6-tri-O-benzoyl-4-O-[2,3,6-tri-O-benzoyl-4-O-(3,4,6-tri-O-benzoyl-2-O-triisopropylsilyl-α-d-galactopyranosyl)-β-d-galactopyranosyl]-β-d-glucopyranoside (27) R_f = 0.26, light PE–EtOAc (3:1). [α]_D ²³ +71.2 (c 1.0, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 0.72–0.92 (m, 21 H, 3 × i-Pr), 2.17 (dt~p, J = 6.1 Hz, 2 H, CH₂), 3.71 (t, J = 6.3 Hz, 2 H, CH₂Cl), 3.85–3.91 (m, 1 H, H-5^II), 3.97 (t, J = 5.9 Hz, 2 H, CH₂O), 4.03 (ddd, J ₅,_6b = 1.9 Hz, J ₅,_6a = 5.7 Hz, J ₄,₅ = 9.8 Hz, 1 H, H–5^I), 4.15 (dd, J ₅,_6a = 6.8 Hz, J _6a,_6b = 11.8 Hz, 1 H, H-6^IIa), 4.30 (dd, J ₅,_6a = 7.4 Hz, J _6a,_6b = 11.1 Hz, 1 H, H-6^IIIa), 4.32 (mt, J = 9.2 Hz, 1 H, H-4^I), 4.49–4.56 (m, 3 H, H-6^Ia, H-4^II, H-2^III), 4.59 (dd, J ₅,_6b = 5.0 Hz, J _6a,_6b = 11.8 Hz, 1 H, H-6^IIb), 4.64 (dd, J ₅,_6b = 6.1 Hz, J _6a,_6b = 11.1 Hz, 1 H, H-6^IIIb), 4.73 (dd, J ₅,_6b = 1.9 Hz, J _6a,_6b = 11.8 Hz, 1 H, H-6^Ib), 4.77–4.82 (m, 1 H, H-5^III), 4.97 (d, J ₁,₂ = 7.7 Hz, 1 H, H-1^II), 5.10 (d, J ₁,₂ = 7.6 Hz, 1 H, H-1^I), 5.29 (d, J ₁,₂ = 3.2 Hz, 1 H, H-1^III), 5.38 (dd, J ₃,₄ = 2.6 Hz, J ₂,₃ = 10.7 Hz, 1 H, H-3^II), 5.63 (dd, J ₁,₂ = 7.6 Hz, J ₂,₃ = 9.2 Hz, 1 H, H-2^I), 5.69 (dd, J ₃,₄ = 3.3 Hz, J ₂,₃ = 10.3 Hz, 1 H, H-3^III), 5.82 (dd~t, J = 9.1 Hz, 1 H, H-3^I), 5.88 (dd, J ₁,₂ = 7.7 Hz, J ₂,₃ = 10.7 Hz, 1 H, H-2^II), 5.95 (dd, J ₄,₅ = 1.6 Hz, J ₃,₄ = 3.3 Hz, 1 H, H-4^III), 6.58–6.66 (m, 2 H, OC₆H₄O), 6.81–6.89 (m, 2 H, OC₆H₄O), 7.17–7.24 (m, 2 H, Ph), 7.25–7.62 (m, 25 H, Ph), 7.75–7.81 (m, 2 H, H-2(6) Ph), 7.84–7.91 (m, 2 H, H-2(6) (PhCO)), 7.91–7.96 (m, 4 H, H-2(6) (PhCO)), 7.98–8.02 (m, 4 H, H-2(6) (PhCO)), 8.02–8.06 (m, 2 H, H-2(6) (PhCO)), 8.06–8.10 (m, 2 H, H-2(6) (PhCO)), 8.14–8.19 (m, 2 H, H-2(6) (PhCO)). ¹³C NMR (101 MHz, CDCl₃): δ = 12.5 (CH(CH₃)₂), 17.7 (CH(CH₃)₂), 17.9 (CH(CH₃)₂), 32.2 (CH₂), 41.5 (CH₂Cl), 62.0 (C-6^III), 62.6 (C-6^I), 63.1 (C-6^II), 64.6 (CH₂O), 67.8 (C-5^III), 69.40 (C-2^III or C-4^III), 69.41 (C-4^III or C-2^III), 69.8 (C-2^II), 70.5 (C-3^III), 72.0 (C-2^I), 72.7 (C-3^I), 73.2 (C-5^I), 73.8 (2 C, C-3^II, C-5^II), 74.4 (C-4^II), 76.4 (C-4^I), 99.8 (C-1^III), 100.3 (C-1^I), 100.9 (C-1^II), 115.1 (OC₆H₄O), 118.8 (OC₆H₄O), 128.0 (Ph), 128.1 (Ph), 128.27 (Ph), 128.33 (Ph), 128.47 (Ph), 128.51 (Ph), 128.54 (Ph), 128.8 (Ph), 129.2 (Ph), 129.3 (Ph), 129.46 (Ph), 129.50 (Ph), 129.6 (Ph), 129.75 (Ph), 129.80 (Ph), 129.91 (Ph), 129.95 (Ph), 132.7 (Ph), 132.8 (Ph), 132.99 (Ph), 133.03 (Ph), 133.15 (Ph), 133.22 (2 C, Ph), 133.4 (Ph), 133.5 (Ph), 151.1 (C-1 OC₆H₄O), 154.6 (C-4 OC₆H₄O), 164.7, 165.1, 165.17, 165.19, 165.3, 165.6, 165.7, 165.8, 166.0 (CO). ESI-HRMS: m/z calcd for C₉₉H₉₇ClNaO₂₆Si: 1787.5618; found: 1787.5614 [M + Na]⁺; m/z calcd for C₉₉H₁₀₁ClNO₂₆Si: 1782.6064; found: 1782.6014 [M + NH₄]⁺
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