Functionalized d- and l-Arabino-Pyrrolidines as Potent and Selective Glycosidase Inhibitors

Marianne B. Haarr; Óscar Lopéz; Jóse G. Fernández-Bolaños; Emil Lindbäck; Magne O. Sydnes

doi:10.1055/a-1764-8950

Synthesis, Table of Contents

Synthesis 2022; 54(12): 2916-2926
DOI: 10.1055/a-1764-8950

paper

Functionalized d- and l-Arabino-Pyrrolidines as Potent and Selective Glycosidase Inhibitors

Marianne B. Haarr

^aFaculty of Science and Technology, Department of Chemistry, Bioscience, and Environmental Engineering, University of Stavanger, Kristine Bonnevies vei 22, 4021 Stavanger, Norway

,

Óscar Lopéz

^bDepartamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, C/ Profesor García González, 1, 41012 Sevilla, Spain

,

Jóse G. Fernández-Bolaños

^bDepartamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, C/ Profesor García González, 1, 41012 Sevilla, Spain

,

Emil Lindbäck∗

^aFaculty of Science and Technology, Department of Chemistry, Bioscience, and Environmental Engineering, University of Stavanger, Kristine Bonnevies vei 22, 4021 Stavanger, Norway

,

Magne O. Sydnes∗

^aFaculty of Science and Technology, Department of Chemistry, Bioscience, and Environmental Engineering, University of Stavanger, Kristine Bonnevies vei 22, 4021 Stavanger, Norway

› Author Affiliations

Abstract

All articles of this category

Abstract

The efficient synthesis of enantiomeric pairs of iminosugars including 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) and 1,4-dideoxy-1,4-imino-l-arabinitol (LAB) analogues with an amidine, hydrazide, hydrazide imide, or amide oxime moiety is described. The preparation of DAB and LAB analogues commenced from l-xylose and d-xylose, respectively. The obtained iminosugars are tested against a panel of glycosidases with pharmaceutical relevance, revealing enhanced activity for the DAB analogues in comparison with the LAB analogues. In particular, the d-arabino-configured amidine behaved as a potent (submicromolar range) and selective inhibitor of α-mannosidase.

Key words

iminosugars - glycosidase inhibitors - arabino - pyrrolidine - mannosidase

Full Text

References

References
1 Nash RJ, Bell EA, Williams JM. Phytochemistry 1985; 24: 1620
2 Fleet GW. J, Nicholas SJ, Smith PW, Evans SV, Fellows LE, Nash RJ. Tetrahedron Lett. 1985; 26: 3127
3 Watson AA, Fleet GW. J, Asano N, Molyneux RJ, Nash RJ. Phytochemistry 2001; 56: 265
4 Stütz AE, Wrodnigg TM. Adv. Carbohydr. Chem. Biochem. 2011; 66: 187
5 Asano N, Nash RJ, Molyneux RJ, Fleet GW. J. Tetrahedron: Asymmetry 2000; 11: 1645
6 Campbell LK, Baker DE, Campbell RK. Ann. Pharmacother. 2000; 34: 1291
7 Cox T, Lachmann R, Hollak C, Aerts J, Van Weely S, Hrebícek M, Platt F, Butters T, Dwek R, Moyses C, Gow I. Lancet 2000; 355: 1481
8 Germain DP, Hughes DA, Nicholls K, Bichet DG, Giugliani R, Wilcox WR, Feliciani C, Shankar SP, Ezgu F, Amartino H, Bratkovic D. N. Engl. J. Med. 2016; 375: 545
9 Lillelund VH, Jensen HH, Liang X, Bols M. Chem. Rev. 2002; 102: 515
10 López Ó, Merino-Montiel P, Martos S, González-Benjumea A. In Carbohydrate Chemistry: Chemical and Biological Approaches, Vol. 38. Rauter AP, Lindhorst T. The Royal Society of Chemistry; Cambridge: 2012: 215
11 D’Alonzo D, Guaragna A, Palumbo G. Curr. Med. Chem. 2009; 16: 473
12 Yu C.-Y, Asano N, Ikeda K, Wang M.-X, Butters TD, Wormald MR, Dwek RA, Winters AL, Nash RJ, Fleet GW. J. Chem. Commun. 2004; 1936
13 Asano N, Ikeda K, Yu L, Kato A, Takebayashi K, Adachi I, Kato I, Ouchi H, Takahata H, Fleet GW. J. Tetrahedron: Asymmetry 2005; 16: 223
14 Kato A, Kato N, Kano E, Adachi I, Ikeda K, Yu L, Okamoto T, Banba Y, Ouchi H, Takahata H, Asano N. J. Med. Chem. 2005; 48: 2036
15 Scofield AM, Fellows LE, Nash RJ, Fleet GW. J. Life Sci. 1986; 39: 645
16 Hakansson AE, van Ameijde J, Guglielmini L, Horne G, Nash RJ, Evinson EL, Kato A, Fleet GW. J. Tetrahedron: Asymmetry 2007; 18: 282
17 Lundt I, Madsen R, Al Daher S, Winchester B. Tetrahedron 1994; 50: 7513
18 Ayers BJ, Ngo N, Jenkinson SF, Martínez RF, Shimada Y, Adachi I, Weymouth-Wilson AC, Kato A, Fleet GW. J. J. Org. Chem. 2012; 77: 7777
19 Lindbäck E, Lopez Ó, Tobiesen A, Fernández-Bolaños JG, Sydnes MO. Org. Biomol. Chem. 2017; 15: 8709
20 Haarr MB, Lopéz Ó, Pejov L, Fernández-Bolaños JG, Lindbäck E, Sydnes MO. ACS Omega 2020; 5: 18507
21 de Santana QL. O, Evangelista TC. S, Imhof P, Ferreira SB, Fernández-Bolaños JG, Sydnes MO, Lopéz Ó, Lindbäck E. Org. Biomol. Chem. 2021; 19: 2322
22 Evangelista TC. S, Lopéz Ó, Sydnes MO, Fernández-Bolaños JG, Ferreira SB, Lindbäck E. Synthesis 2019; 51: 4066
23 Gnanesh Kumar BS, Pohlentz G, Schulte M, Mormann M, Siva Kumar N. Glycobiology 2014; 24: 252
24 Ermert P, Vasella A. Helv. Chim. Acta 1991; 74: 2043
25 Kanso R, Striegler S. Carbohydr. Res. 2011; 346: 897
26 Boutellier M, Horenstein BA, Semenyaka A, Schramm VL, Ganem B. Biochemistry 1994; 33: 3994
27 Overkleeft HS, van Wiltenburg J, Pandit UK. Tetrahedron 1994; 50: 4215
28 Stephenson L, Warburton WK, Wilson MJ. J. Chem. Soc. C 1969; 861
29 Vörös A, Mucsi Z, Baán Z, Timári G, Hermecz I, Mizsey P, Finta Z. Org. Biomol. Chem. 2014; 12: 8036
30 Bols M, Hazell RG, Thomsen IB. Chem. Eur. J. 1997; 3: 940
31 Cornish-Bowden A. Biochem. J. 1974; 137: 143

Supplementary Material

Supporting Information