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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.


Linear oligomerisation products from the reaction of monomer 7 under CuAAC conditions identified by HRMS compounds 14–18 were obtained in a combined yield of 26% (Method A) and 36% (Method B).
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fig3: Linear oligomerisation products from the reaction of monomer 7 under CuAAC conditions identified by HRMS compounds 14–18 were obtained in a combined yield of 26% (Method A) and 36% (Method B).

Mentions: The linear oligomeric products eluted on reverse phase HPLC as a single broad peak at ca. 32 min (Fig. 2, HPLC traces A and B). These compounds were well resolved from each other and from the corresponding cyclic oligomers on analytical TLC (Fig. 2, lane L), linear oligomers 14–18 have slightly higher Rf values compared to cyclic product of the same molecular size. Monomer 7 was shown to undergo oligomerisation up to at least a decamer. These analyses alongside isolated yields (see Figs. 2 and 3 and Table S1 in Supplementary data) also illustrate that the lower reaction temperature (room temperature vs 110 °C) favours formation of linear products over the corresponding cyclic isomers. In contrast to reverse phase HPLC, gel permeation chromatography (GPC) on TSK-HW40S enabled separation of linear oligomers up to the pentamer (Fig. 3). It should be noted that these linear compounds contain unreacted azido and alkyne terminal groups capable of further reactions even in the absence of Cu(I) catalyst. This gave rise to complications during handling and storage due to spontaneous cyclisation and oligomerisation of purified compounds (data not shown).


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)

Linear oligomerisation products from the reaction of monomer 7 under CuAAC conditions identified by HRMS compounds 14–18 were obtained in a combined yield of 26% (Method A) and 36% (Method B).
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

fig3: Linear oligomerisation products from the reaction of monomer 7 under CuAAC conditions identified by HRMS compounds 14–18 were obtained in a combined yield of 26% (Method A) and 36% (Method B).
Mentions: The linear oligomeric products eluted on reverse phase HPLC as a single broad peak at ca. 32 min (Fig. 2, HPLC traces A and B). These compounds were well resolved from each other and from the corresponding cyclic oligomers on analytical TLC (Fig. 2, lane L), linear oligomers 14–18 have slightly higher Rf values compared to cyclic product of the same molecular size. Monomer 7 was shown to undergo oligomerisation up to at least a decamer. These analyses alongside isolated yields (see Figs. 2 and 3 and Table S1 in Supplementary data) also illustrate that the lower reaction temperature (room temperature vs 110 °C) favours formation of linear products over the corresponding cyclic isomers. In contrast to reverse phase HPLC, gel permeation chromatography (GPC) on TSK-HW40S enabled separation of linear oligomers up to the pentamer (Fig. 3). It should be noted that these linear compounds contain unreacted azido and alkyne terminal groups capable of further reactions even in the absence of Cu(I) catalyst. This gave rise to complications during handling and storage due to spontaneous cyclisation and oligomerisation of purified compounds (data not shown).

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.