Synlett
DOI: 10.1055/a-1523-1638
letter

Synthesis of a Glycosylphosphatidylinositol (GPI) Fragment as a Potential Substrate for Mannoprotein Transglycosidases

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.


Abstract

A glycophosphatidylinositol tetrasaccharide fragment was synthesized to mimic the core features of primary model, that of Saccharomyces cerevisiae. The salient feature of this approach is centered on the quick access to various α-1,2- and α-1,6-mannosyl and α-1,4-glycosyl linkages by using simple glycosylation and protective-group techniques. 1D and 2D-J-resolved NMR spectroscopy was used to verify the α-configuration of the new linkages. The tetrasaccharides obtained in this work are useful for examining fungal cell-wall glycoprotein cross-linking by transglycosidase enzymes for antifungal drug development.

Supporting Information



Publication History

Received: 26 March 2021

Accepted after revision: 04 June 2021

Publication Date:
04 June 2021 (online)

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
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  • 32 GPI Tetrasaccharide Fragment 25 29 Tetrasaccharide polyol 24 (4 mg, 5.54 μmol) was heated with hydrazine hydrate (0.5 mL) at 120 °C with stirring overnight. The solution was co-evaporated in vacuo with toluene (2 × 0.5 mL) and the residue was purified by flash chromatography [silica gel, 0.5% Et3N in EtOAc–MeOH–H2O (7:2:1 to 1:9:0)], followed by reverse-phase chromatography [silica gel, H2O–MeCN (1:0 to 19:1 to 9:1), 200 μL fractions] to give a white solid; yield: 2.8 mg, (68%); mp 163 °C. 1H NMR (400 MHz, D2O): δ = 5.09 (s, 1 H, H1D), 5.01 (s, 1 H, H1B), 4.90 (s, 1 H, H1C peak suppressed), 4.75 (s, 1 H, H1A peak suppressed), 3.95–4.42 [m, 23 H, H(3,4,5,6,6′)A, H(2,3,4,5,6,6′)B,C,D], 3.28 (s, 3 H, OMe), 2.65 (dd, J 1,2 = 3.7, J 2,3 = 10.3 Hz, 1 H, H2A). 13C NMR (100 MHz, CDCl3): δ = 102.3 (C1D), 101.8 (C1B), 99.2 (C1A), 98.3 (C1C), 78.7, 77.3, 73.7, 73.2, 72.7, 72.2, 70.7, 70.4, 70.3, 70.2, 69.9, 66.9, 66.9, 66.5, 66.3, 61.1, 60.9, 60.8, 55.2, 54.8 [C(2,3,4,5,6)A,B,C,D]. HRMS (ESI+): m/z [M + H]+ calcd for C25H46NO20: 680.25970; found: 680.26077.