Synthesis of S-Linked N-Acetylneuraminic Acid Derivatives via Photoinduced Thiol–ene and Thiol–yne Couplings

Abstract

Thio-linked mono- and bivalent mimetics of α(2→3) and α(2→6)-linked sialosides were prepared by photoinduced hydrothiolation of alkenes and alkynes with the 2-mercapto sialic acid. Thiosialylation of 6-O-allyl- or 3-O-allyl-substituted galactose derivatives has been carried out by the thiol–ene click reaction. Double thiosialylation has also been achieved via thiol–yne chemistry using propargylated galactose derivatives as the alkyne components and the peracetylated 2-mercapto sialic acid as the thiol.

Key words

carbohydrates - N-acetylneuraminic acid - radical additions - thiol–ene/thiol–yne coupling - thiosialosides

• References and Notes

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• 16 NMR Data for Compound 5 ¹H NMR (500 MHz, CDCl₃): δ = 6.43* (d, 0.7 H, J = 15.5 Hz, SCH=CHCH₂), 6.41* (d, 0.3 H, J = 8.5 Hz, SCH=CHCH₂), 5.93–5.88 (m, 1 H, SCH=CHCH₂), 5.59–5.52 (m, 2 H), 5.39–5.31 (m, 3 H), 4.89–4.85 (m, 1 H), 4.60–4.57 (m, 1 H), 4.32–4.24 (m, 3 H), 4.16–4.03 (m, 4 H), 3.96–3.88 (m, 2 H), 3.85–3.78 (m, 4 H), 3.63–3.53 (m, 2 H), 2.76–2.71 (m, 1 H), 2.20–1.87 (m, 15 H), 1.54, 1.53, 1.44, 1.43, 1.34, 1.33, 1.32 (7 × s, 12 H, CH_3,ip) ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 170.7, 170.5, 170.2, 169.9, 168.0, 167.9 (CO), 132.3, 128.5, 121.2, 120.3 (SCH=CHCH₂), 109.0, 108.4 [(CH₃)₂ C], 96. 2 (C-1), 84.2, 83.3 (2 × C-2′), 75.0, 74.3, 74.2, 71.0, 70.5, 70.4, 70.2, 69.5, 69.4, 68.9, 68.5, 67.6, 67.3, 67.2, 66.7, 66.6 (skeleton carbons), 71.1, 68.8, 68.5, 67.7, 62.1, 62.0 (C-6, C-9′, CH₂), 53.0, 52.9 (2 × COOCH₃), 49.0 (2 × C-5′), 37.5, 37.3 (2 × C-3′), 25.9, 25.8, 24.8, 24.3, 22.9, 21.0, 20.6 (CH_3,Ac, CH_3,NAc, CH₃) ppm; *overlapping signals.
• 17 Dondoni and co-workers also observed the lack of stereoselectivity during photoinduced addition of glucosyl or galactosyl thiols to alkynyl peptides; see ref. 8a.
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• 21 NMR Data for Compound 12 ¹H NMR (360 MHz, CDCl₃): δ = 8.06–7.26 (m, 10 H, arom.), 5.60–5.43 (m, 3 H), 5.30–5.27 (m, 2 H), 5.14–5.12 (m, 1 H), 4.85–4.75 (m, 2 H), 4.57 (d, 1 H, J = 7.9 Hz), 4.50 (t, 1 H, J = 10.0 Hz), 4.45–4.35 (m, 3 H), 4.29–4.24 (m, 1 H), 4.15–3.87 (m, 8 H), 3.80–3.49 (m, 16 H), 2.60–2.54 (m, 2 H), 2.14–1.25 (m, 23 H) ppm. ¹³C NMR (90 MHz, CDCl₃): δ = 170.9, 170.6, 170.1, 170.0 (6 C, CO), 133.5-126.4 (10 C, arom), 102.3, (2 C, C_ac), 101.1 (C-1), 83.3 (C-2′), 78.5, 73.9, 73.2, 69.6, 68.3, 67.1, 66.7, 66.4 (8 C, skeleton carbons), 70.5, 69.3, 69.1, 68.0, 66.8 (5 C, 4 × CH₂, C-6), 63.0 (C-9′), 52.8 (C-5′), 35.1, 32.7, 29.3, 29.2, 29.1, 25.8, 25.7, 25.5, 23.8, 23.7 (10 C, CH₂), 23.1 (CH_3,NHAc), 21.2, 20.8 (4 C, CH_3,Ac) ppm.
• 22 Giguère D, Patnam R, Bellefleur M.-A, St-Pierre C, Sato S, Roy R. Chem. Commun. 2006; 2379
• 23 NMR Data for Compound 15 ¹H NMR (500 MHz, CDCl₃): δ = 6.46 (d, 0.17 H, J = 9.5 Hz, SCH=CHCH₂), 6.35 (d, 0.83 H, J = 15.5 Hz, SCH=CHCH₂), 5.72–5.69 (m, 1 H, SCH=CHCH₂), 5.48–5.31 (m, 3 H), 5.04–5.01 (m, 1 H), 4.90–4.85 (m, 2 H), 4.51–4.49 (m, 2 H), 4.40–4.17 (m, 3 H), 4.15–4.05 (m, 3 H), 4.01–3.75 (m, 10 H), 3.60–3.42 (m, 3 H), 2.75–2.72 (m, 2 H), 2.22–1.84 (m, 24 H), 1.59–1.28 (m, 14 H) ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 170.7, 170.5, 170.4, 170.3, 170.2, 170.1, 170.0, 169.8, 169.4, 169.3, 168.1, 167.7 (CO), 130.5, 128.4, 122.2, 121.9 (CH), 102.3 (C_ac), 101.2 (C-1), 77.2, 77.0, 76.7, 76.6, 76.1, 74.9, 74.4, 74.1, 70.7, 70.4, 69.8, 69.2, 68.8, 68.0, 67.3, 67.0, 66.7, 66.5, 65.9 (skeleton carbons), 69.5, 69.4, 67.5 (CH₂), 62.2, 62.1, 61.9 (C-6), 53.0 (OCH₃), 49.2, 49.0 (C-5), 37.5, 37.3, 35.1, 29.3, 29.1, 25.74 (CH₂), 25.6, 23.7, 23.0, 21.1, 21.0, 20.9, 20.7, 20.6 (CH₃) ppm