The First Synthesis of N-Man-Trp: Alternative Mannosylation Modification of Protein

Abstract

A novel protein modification, N-mannosyl tryptophan (N-Man-Trp) was synthesized in a stereoselective manner.

Key words

carbohydrate - glycopeptides - glycoamino acid - mannosyl tryptophan - total synthesis

References and Notes

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19

Epimerization at chiral center was observed when NaOH or TBAF was used as reagent.

21

¹H NMR (600 MHz, D₂O, KH₂PO₄-Na₂HPO₄ buffer pH 7, dioxane 3.75 ppm as a ref., 25 °C): δ = 7.74 (d, J = 8.1 Hz, 1 H, C-5), 7.72 (d, J = 8.1 Hz, 1 H, C-8), 7.44 (s, 1 H, C-2), 7.36 (dd, J = 8.1, 7.1 Hz, 1 H, C-7), 7.27 (dd, J = 8.1, 7.1 Hz, 1 H, C-6), 6.03 (d, J = 4.5 Hz, 1 H, C′-1), 4.68 (dd, J = 4.5, 3.5 Hz, 1 H, C′-2), 4.21 (dd, J = 6.5, 3.5 Hz, 1 H, C′-3), 4.07 (dd, J = 8.1, 5.0 Hz, 1 H, CH of Trp) 4.00 (dd, J = 12.6, 7.6 Hz, 1 H, C′-6), 3.92 (dd, J = 6.5, 6.5 Hz, 1 H, C′-4), 3.76 (dd, J = 12.6, 3.0 Hz, 1 H, C′-6), 3.55 (ddd, J = 7.6, 6.5, 3.0 Hz, 1 H, C′-5), 3.47 (dd, J = 15.1, 5.0 Hz, 1 H, CH₂ of Trp), 3.31 (dd, J = 15.1, 8.1 Hz, 1 H, CH₂ of Trp). ¹³C NMR (125 MHz, D₂O, KH₂PO₄-Na₂HPO₄ buffer pH 7): δ = 175.0 (C, CO₂H), 137.5 (C, C-9), 128.5 (C, C-4), 123.5 (CH, C-7), 125.8 (CH, C-2), 121.4 (CH, C-6), 119.6 (CH, C-5), 112.3 (CH, C-8), 110.2 (C, C-3), 82.4 (CH, C′-1), 77.5 (CH, C′-5), 71.8 (CH, C′-3), 68.6 (CH, C′-4), 68.3 (CH, C′-2), 60.5 (CH₂, C′-6), 55.4 (CH, CH of Trp), 26.86 (CH₂, CH₂ of Trp); C-N linkage between anomeric carbon and indole nitrogen is confirmed by HMBC analysis; [α]_D ²⁴ -17 (c 0.1, H₂O).