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Chemoenzymatic Synthesis of a Sialylated Undecasaccharide–Asparagine Conjugate†‡
Dr. Carlo Unverzagt,
Corresponding Author
Dr. Carlo Unverzagt
Institut für Organische Chemie und Biochemie der Technischen Universität München, Lichtenbergstrasse 4, D-85748 Garching (Germany) Fax: Int. code +(89)2891-3210
Institut für Organische Chemie und Biochemie der Technischen Universität München Lichtenbergstrasse 4, D-85748 Garching (Germany) Fax: Int. code +(89)2891-3210Search for more papers by this authorDr. Carlo Unverzagt,
Corresponding Author
Dr. Carlo Unverzagt
Institut für Organische Chemie und Biochemie der Technischen Universität München, Lichtenbergstrasse 4, D-85748 Garching (Germany) Fax: Int. code +(89)2891-3210
Institut für Organische Chemie und Biochemie der Technischen Universität München Lichtenbergstrasse 4, D-85748 Garching (Germany) Fax: Int. code +(89)2891-3210Search for more papers by this author†
This work was supported by the Deutsche Forschungsgemeinschaft and by the Leonhard-Lorenz-Stiftung, and was presented at the Eighth European Carbohydrate Symposium 1995 in Seville (Spain). I would like to thank the Hoechst AG and Boehringer Mannheim for funding and Prof. Dr. H. Kessler for his generous support.
‡
Dedicated to Professor Hans Paulsen on the occasion of his 75th birthday
Graphical Abstract
A partial structure of many glycoproteins, the complex undecasaccharide–asparagine conjugate 1 was obtained for the first time by total synthesis. Crucial to the synthesis was a combination of modern chemical and enzymatic methods, which reduced the overall number of steps and allowed efficient deprotonation.
References
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1: 5.6 mg yield (86% based on 13); [α]
= −9.1° (0.5, H2O); 1H NMR (500 MHz, D2O): δ = 5.19 (d, J1, 2 < 1.0 Hz, 1 H, H-14), 5.12 (d, J1, 2 = 9.7 Hz, 1 H, H-11), 5.01 (d, J1, 2 < 1.0 Hz, 1 H, H-14′), 4.83 (d, J1, 2 < 1.0 Hz, 1 H, H-13), 4.69–4.65 (m, 3 H, H-12, H-15, H-15′), 4.505, 4.502 (2d, J1, 2 = 7.8 Hz, 2 H, H-16, H-16′), 4.31 (dd, J2, 3 = 1.9 Hz, H-23), 4.25 (dd, J2, 3 = 1.9 Hz, H-24), 4.17 (dd, J2, 3 = 1.9 Hz, H-24′), 3.00 (dd, Jgem = 17.2 Hz, Jvic = 4.2 Hz, 1 H, β-CHa-Asn), 2.92 (dd, Jvic = 7.0 Hz, 1 H, β-CHb-Asn), 2.76–2.71 (m, 2H, H-3eqN, H-3eqN′), 2.14, 2.13, 2.09, 2.07, 2.06 (5s, 18H, NAc), 1.78 (t, Jgem = 12.1 Hz, 2 H, H-3axN, H-3axN′). 13C NMR (125 MHz, D2O, [D6] DMSO as internal standard; the chemical shifts were determined by an HMQC spectum): δ = 104.8 C-16, C-16′, 102.6 C-12, 101.8 C-13, 100.7 C-14, 100.6 C-15, C-15′, 98.1 C-14′, 81.9 C-45, C-45′, 81.8 C-33, 80.9 C-42, 80.2 C-41, 79.4 C-11, 77.8 C-24, 77.6 C-24′, 77.5 C-51, 75.7 C-52, C-52, C-53, C-55, C-55′, 75.0 C-56, C-56′, 74.9 C-54, 74.1 C-54′, 74.0 C-31, 73.8 C-36, C-36′, C-3N, C-3N′, 73.3 C-32, C-35, C-35′, 73.0 C-8N, C-8N′, 72.0 C-26, C-26′, 71.4 C-23, 70.7 C-34, C-34′, 69.7 C-7N, C-7N′, 69.6 C-46, C-46′, 69.4 C-4N, C-4N′, 68.6 C-44, C-44′, 67.1 C-63, 67.0 C-43, 64.6 C-66, C-66′, 64.0 C-9N, C-9N′, 62.9 C-64, C-64′, 61.5 C-65, C-65′, 61.2 C-62, 61.1 C-61, 56.2 C-22, 55.9 C-25, C-25′, 54.9 C-21, 53.2 C-5N, C-5N′, 52.1 αC-Asn, 39.0 C-3N, C-3N′, 36.3 βC-Asn, 23.9, 23.8, 23.7 NAc.
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