Avviso di seminario
Venerdì 17 Aprile 2015 – ore 11:30
Aula 2025, Edificio U3, 2° piano
Synthesis and Applications of Cyclopeptide-Based Multivalent Homoand Hetero-glycoclusters as molecular brushes.
Synthesis and Studies of C-2 and C-4 Branched Saccharides.
Relatore: Dr. Gour Chand Daskhan
Département de Chimie Moléculaire, UMR-CNRS 5250 & ICMG FR 2607, Université Joseph Fourier,
Grenoble, Cedex 9, France
Abstract: Multivalent carbohydrate-protein interactions play a crucial role in diverse range of biological
1
events. Synthetic homoglycolusters constituted with multiple copies of identical sugar units on the synthetic
scaffolds such as carbohydrates, cyclodextrins, calixarenes, peptides and polymers have contributed
extensively to disclose many facets of recognition processes. However, recent reports highlighted that
presence of different sugar units on the same scaffold may also indispensible to assess the impact of
2
3
heterogeneity in protein-binding processes. In this context, using cyclopetide as molecular template, we
synthesized series of multivalent homo-and hetero-glycoclusters and their lectin binding potency was further
investigated. Synthesis was accomplished by employing chemoselective ligations strategy as a key reaction
by using various “click reactions” such as oxime ligation (OL), Cu(I) catalysed 1,3-dipolar cycloaddition
(CuAAC), tihiol-ene coupling (TEC), thiol-chloroacetyl coupling (TCC), and disulfide exchange (S-S) (Figure
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A). Detailed synthesis of the carbohydrate precursors, clickable cyclopeptide scaffolds, and their couplings
and lectin binding studies will be presented.
Carbohydrates are polyfunctional biomolecules and can be modified in numerous ways. Chemical
modifications of monosaccharides led to the formation of valuable building blocks in carbohydrate chemistry.
In the event, a new monosaccharide derivative, namely, 4-deoxy-4-C-hydroxymethyl glucopyranoside (C-4
branched sugar), was synthesized and subsequently utilized for the synthesis of series of glycosidic bond
5-6
expanded linear and cyclic-oligosaccharide analogues. In addition, a new route to synthesize 2-deoxy-2-C7
alkyl glycal derivatives (C-4 branched sugar) was also established from 2-hydroxy glycal ester. The last part
of the presentation will includes synthesis and studies of C-2 and C-4 branched carbohydrates in detail
(Figure B).
click functions
(A)
Gly
Pro
Lys
Lys
Ala
Lys
Lys
Lys
-CHO
Pro
Gly
clickable cyclopeptide scaffolds
ONH2
-SH
O
-SH
Orthogonal chemoselective
ligations
BnO
Lys
Pro
OBn
O
OBn
HO
BnO
OBn
OBn
O
OBn
O
OBn SEt
Lys
Lys
O
Pro
Gly
O HO
OH
HO
O
OBn
O
BnO
Lys
Ala
Homo-and heteroglycoclusters
HO
(B)
HO
Lys
Gly
O
HO
OH
HO
O
OH
O
OH
OH OHO
O HO
Figure 1: Synthesis of homo-and heteroglycoclusters (A) and C-4 branched carbohydrate analogues (B).
References
1. Varki, A. Glycobiology 1993, 3, 97-130.
2. (a) Horan, N.; Yan, L.; Whitesides, G. M.; Kahne, D. Proc. Natl. Acad. Sci. U. S. A. 1999, 96, 11782-11786; (b) Jimenez Blanco, J. L.; Ortiz Mellet, C.;
Garcia Fernandez, J. M. Chem. Soc. Rev. 2013, 42, 4518-4531.
3. Galan, M. C.; Dumy, P.; Renaudet, O. Chem. Soc. Rev. 2013, 42, 4599-4612.
4. (a) Křenek, K.; Gažák, R.; Daskhan, G. C.; Garcia, J.; Fiore, M.; Dumy, P.; Šulc, M.; Křen, V.;
Renaudet, O. Carbohydr. Res. 2014, 393, 9-14; (b) Fiore, M.; Daskhan, G. C.; Thomas, B.; Renaudet,
O. Beilstein J. Org. Chem. 2014, 10, 1557-1563; (c) Thomas, B.; Fiore, M.; Daskhan, G. C.; Spinel, N.
N.; Renaudet, O.Chem. Commun. 2015, 51, 5436-5439; (d) manuscripts under preparation.
5. Daskhan, G. C.; Jayaraman, N. Carbohydr. Res. 2011, 346, 2394-2400.
6. Daskhan, G. C.; Jayaraman, N. Chem. Commun. 2014, 50, 8554-8557.
7. Daskhan, G. C.;Jayaraman, N.J. Org. Chem. 2012, 77, 2185-2191.
Ospite: Prof. Francesco Nicotra