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Click chemistry oligomerisation of azido-alkyne-functionalised galactose accesses triazole-linked linear oligomers and macrocycles that inhibit Trypanosoma cruzi macrophage invasion.

Campo VL, Ivanova IM, Carvalho I, Lopes CD, Carneiro ZA, Saalbach G, Schenkman S, da Silva JS, Nepogodiev SA, Field RA - Tetrahedron (2015)

Bottom Line: Reaction of 2-(2-(2-azidoethoxy)ethoxy)ethyl 6-O-(prop-2-ynyl)-β-d-galactopyranoside (7) under CuAAC conditions gives rise to mixed cyclic and linear triazole-linked oligomers, with individual compounds up to d.p. 5 isolable, along with mixed larger oligomers.The triazole-linked oligomers-pseudo-galactooligomers-were demonstrated to be acceptor substrates for the multi-copy cell surface trans-sialidase of the human parasite Trypanosoma cruzi.In addition, these multivalent TcTS ligands were able to block macrophage invasion by T. cruzi.

View Article: PubMed Central - PubMed

Affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Av. Café S/N, CEP 14040-903, Ribeirão Preto, SP, Brazil.

ABSTRACT

Reaction of 2-(2-(2-azidoethoxy)ethoxy)ethyl 6-O-(prop-2-ynyl)-β-d-galactopyranoside (7) under CuAAC conditions gives rise to mixed cyclic and linear triazole-linked oligomers, with individual compounds up to d.p. 5 isolable, along with mixed larger oligomers. The linear compounds resolve en bloc from the cyclic materials by RP HPLC, but are separable by gel permeation chromatography. The triazole-linked oligomers-pseudo-galactooligomers-were demonstrated to be acceptor substrates for the multi-copy cell surface trans-sialidase of the human parasite Trypanosoma cruzi. In addition, these multivalent TcTS ligands were able to block macrophage invasion by T. cruzi.

No MeSH data available.


Cyclisation and oligomerisation of monomer 7 (1M in DMF), through CuAAC employing Method A (Cu(I), 110 °C) and Method B (Cu(I), room temperature). Yields (%) for Method A and Method B.
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sch2: Cyclisation and oligomerisation of monomer 7 (1M in DMF), through CuAAC employing Method A (Cu(I), 110 °C) and Method B (Cu(I), room temperature). Yields (%) for Method A and Method B.

Mentions: Once synthesised, the reactivity of azido-alkyne-functionalised galactose monomer 7 was tested under CuAAC conditions—at 1 M concentration in DMF with CuSO4/Cu turnings either at 110 °C (using microwave irradiation; Method A) or at ambient temperature (Method B). The progress of both reactions could conveniently be followed by TLC analysis. The reaction using Method A was complete after 30 min, compared to 2 days for Method B. TLC analysis showed formation of multiple common products, consistent with the intended oligomerisation, while different relative spot intensities were evident from the two methods (Fig. 2, TLC lanes A and B). The reaction mixtures from both methods were concentrated under reduced pressure, redissolved in water and submitted to reverse phase (RP) HPLC purification. This allowed straightforward separation of cyclic from linear products, as well as resolution of the variously sized cyclic oligomers from each other (Fig. 2, HPLC traces A and B) resulting in samples of cyclic monomer 8, cyclic dimer 9, cyclic trimer 10, cyclic tetramer 11, cyclic pentamer 12 and cyclic hexamer 13, along with mixed linear oligomers, which interestingly did not resolve under the reverse phase HPLC conditions employed to separate the corresponding cyclic materials (Scheme 2). The formation of cyclic 1,4-triazole-linked structures was confirmed by virtue of singlet signals of triazole CH protons at δ 8.10 ppm38 and the absence of propargyl CH signals at δ 2.83 in 1H NMR spectra.


Click chemistry oligomerisation of azido-alkyne-functionalised galactose accesses triazole-linked linear oligomers and macrocycles that inhibit Trypanosoma cruzi macrophage invasion.

Campo VL, Ivanova IM, Carvalho I, Lopes CD, Carneiro ZA, Saalbach G, Schenkman S, da Silva JS, Nepogodiev SA, Field RA - Tetrahedron (2015)

Cyclisation and oligomerisation of monomer 7 (1M in DMF), through CuAAC employing Method A (Cu(I), 110 °C) and Method B (Cu(I), room temperature). Yields (%) for Method A and Method B.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4542550&req=5

sch2: Cyclisation and oligomerisation of monomer 7 (1M in DMF), through CuAAC employing Method A (Cu(I), 110 °C) and Method B (Cu(I), room temperature). Yields (%) for Method A and Method B.
Mentions: Once synthesised, the reactivity of azido-alkyne-functionalised galactose monomer 7 was tested under CuAAC conditions—at 1 M concentration in DMF with CuSO4/Cu turnings either at 110 °C (using microwave irradiation; Method A) or at ambient temperature (Method B). The progress of both reactions could conveniently be followed by TLC analysis. The reaction using Method A was complete after 30 min, compared to 2 days for Method B. TLC analysis showed formation of multiple common products, consistent with the intended oligomerisation, while different relative spot intensities were evident from the two methods (Fig. 2, TLC lanes A and B). The reaction mixtures from both methods were concentrated under reduced pressure, redissolved in water and submitted to reverse phase (RP) HPLC purification. This allowed straightforward separation of cyclic from linear products, as well as resolution of the variously sized cyclic oligomers from each other (Fig. 2, HPLC traces A and B) resulting in samples of cyclic monomer 8, cyclic dimer 9, cyclic trimer 10, cyclic tetramer 11, cyclic pentamer 12 and cyclic hexamer 13, along with mixed linear oligomers, which interestingly did not resolve under the reverse phase HPLC conditions employed to separate the corresponding cyclic materials (Scheme 2). The formation of cyclic 1,4-triazole-linked structures was confirmed by virtue of singlet signals of triazole CH protons at δ 8.10 ppm38 and the absence of propargyl CH signals at δ 2.83 in 1H NMR spectra.

Bottom Line: Reaction of 2-(2-(2-azidoethoxy)ethoxy)ethyl 6-O-(prop-2-ynyl)-β-d-galactopyranoside (7) under CuAAC conditions gives rise to mixed cyclic and linear triazole-linked oligomers, with individual compounds up to d.p. 5 isolable, along with mixed larger oligomers.The triazole-linked oligomers-pseudo-galactooligomers-were demonstrated to be acceptor substrates for the multi-copy cell surface trans-sialidase of the human parasite Trypanosoma cruzi.In addition, these multivalent TcTS ligands were able to block macrophage invasion by T. cruzi.

View Article: PubMed Central - PubMed

Affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Av. Café S/N, CEP 14040-903, Ribeirão Preto, SP, Brazil.

ABSTRACT

Reaction of 2-(2-(2-azidoethoxy)ethoxy)ethyl 6-O-(prop-2-ynyl)-β-d-galactopyranoside (7) under CuAAC conditions gives rise to mixed cyclic and linear triazole-linked oligomers, with individual compounds up to d.p. 5 isolable, along with mixed larger oligomers. The linear compounds resolve en bloc from the cyclic materials by RP HPLC, but are separable by gel permeation chromatography. The triazole-linked oligomers-pseudo-galactooligomers-were demonstrated to be acceptor substrates for the multi-copy cell surface trans-sialidase of the human parasite Trypanosoma cruzi. In addition, these multivalent TcTS ligands were able to block macrophage invasion by T. cruzi.

No MeSH data available.