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

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.

Key words

oligosaccharides - glycosylation - medicinal chemistry

Publication History

Received: 26 March 2021

Accepted after revision: 04 June 2021

Accepted Manuscript online:
04 June 2021

Article published online:
23 August 2021

• References and Notes

• 1a Lipke PN, Ovalle RC. J. Bacteriol. 1998; 180: 3735
• 1b de Nobel H, Lipke PN. Trends Cell. Biol. 1994; 4: 42
• 2 Ferguson MA, Low MG, Cross GA. J. Biol. Chem. 1985; 260: 14547
• 3 Ferguson MA, Homans SW, Dwek RA, Rademacher TW. Science 1988; 239: 753
• 4 McConville MJ, Collidge TA, Ferguson MA, Schneider P. J. Biol. Chem. 1993; 268: 15595
• 5 Lu J, Jayaprakash KN, Fraser-Reid B. Tetrahedron Lett. 2004; 45: 879
• 6 Ferguson MA. J, Williams AF. Annu. Rev. Biochem. 1988; 57: 285
• 7a Fankhauser C, Homans SW, Thomas-Oates JE, McConville MJ, Desponds C, Conzelmann A, Ferguson MA. J. Biol. Chem. 1993; 268: 26365
• 7b Conzelmann A, Puoti A, Lester RL, Desponds C. EMBO J. 1992; 11: 457
• 8 Futerman AH, Low MG, Ackermann KE, Sherman WR, Silman I. Biochem. Biophys. Res. Commun. 1985; 129: 312
• 9 Tse AG, Barclay AN, Watts A, Williams AF. Science 1985; 230: 1003
• 10 Murakata C, Ogawa T. Tetrahedron Lett. 1990; 31: 2439
• 11 Mayer TG, Kratzer B, Schmidt RR. Angew. Chem., Int. Ed. Engl. 1994; 33: 2177
• 12 Tsai Y.-H, Götze S, Azzouz N, Hahm HS, Seeberger PH, Varon Silva D. Angew. Chem. Int. Ed. 2011; 50: 9961
• 13 Belz T, Williams SJ. Carbohydr. Res. 2016; 429: 38
• 14 Belz T, Jin Y, Coines J, Rovira C, Davies GJ, Williams SJ. Chem. Commun. 2017; 53: 9238
• 15 Thompson AJ, Speciale G, Iglesias-Fernández J, Hakki Z, Belz T, Cartmell A, Spears RJ, Chandler E, Temple MJ, Stepper J, Gilbert HJ, Rovira C, Williams SJ, Davies GJ. Angew. Chem. Int. Ed. 2015; 54: 5378
• 16 Ma Z, Zhang J, Kong F. Carbohydr. Res. 2004; 339: 1761
• 17 Lindhorst TK. J. Carbohydr. Chem. 1997; 16: 237
• 18 Crich D, Dudkin V. J. Am. Chem. Soc. 2001; 123: 6819
• 19 Böeseken J, Tellegen F. Recl. Trav. Chim. Pays-Bas 1938; 57: 133
• 20 Hense A, Ley SV, Osborn HM. I, Owen DR, Poisson J.-F, Warriner SL, Wesson KE. J. Chem. Soc., Perkin Trans. 1 1997; 2023
• 21 Burugupalli S, Shah S, van der Peet PL, Arora S, White JM, Williams SJ. Org. Biomol. Chem. 2016; 14: 97
• 22 Mitsunobu O. Synthesis 1981; 1
• 23 Weinges K, Haremsa S, Maurer W. Carbohydr. Res. 1987; 164: 453
• 24 Cao B, White JM, Williams SJ. Beilstein J. Org. Chem. 2011; 7: 369
• 25 Geyer K, Seeberger PH. Helv. Chim. Acta 2007; 90: 395
• 26 Fischer E, Zemplén G. In Untersuchungen Über Kohlenhydrate und Fermente II (1908–1919) . Fischer E. Springer; Berlin: 1922: 234
• 27 Dilbeck GA, Field L, Gallo AA, Gargiulo RJ. J. Org. Chem. 1978; 43: 4593
• 28a Grehn L, Gunnarsson K, Ragnarsson U. Acta Chem. Scand., Ser. B 1986; 40: 745
• 28b Grehn L, Gunnarsson K, Ragnarsson U. J. Chem. Soc., Chem. Commun. 1985; 1317
• 29 Svejgaard L, Fuglsang H, Jensen PB, Kelly NM, Pedersen H, Andersen K, Ruhland T, Jensen KJ. J. Carbohydr. Chem. 2003; 22: 179
• 30a Xing Y, Ning J. Tetrahedron: Asymmetry 2003; 14: 1275
• 30b Ma Z, Zhang J, Kong F. Tetrahedron: Asymmetry 2003; 14: 2595
• 31 Bock K, Pedersen C. J. Chem. Soc., Perkin Trans. 2 1974; 293
• 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, H1^D), 5.01 (s, 1 H, H1^B), 4.90 (s, 1 H, H1^C peak suppressed), 4.75 (s, 1 H, H1^A 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, H2^A). ¹³C NMR (100 MHz, CDCl₃): δ = 102.3 (C1^D), 101.8 (C1^B), 99.2 (C1^A), 98.3 (C1^C), 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.