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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.


Synthetic route to azido-alkyne-containing galactose monomer 7. Reagents and conditions: a) BzCl, Py, 81%; b) NH3, MeOH/THF (7:3), 64%; c) Cl3CCN, DBU, CH2Cl2, 85%; d) 2-(2-(2-chloroethoxy)ethoxy)ethanol, TMSOTf, CH2Cl2, 85%; e) NaN3, NaI, DMF, 97%; f) NaOMe, MeOH, 92%.
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sch1: Synthetic route to azido-alkyne-containing galactose monomer 7. Reagents and conditions: a) BzCl, Py, 81%; b) NH3, MeOH/THF (7:3), 64%; c) Cl3CCN, DBU, CH2Cl2, 85%; d) 2-(2-(2-chloroethoxy)ethoxy)ethanol, TMSOTf, CH2Cl2, 85%; e) NaN3, NaI, DMF, 97%; f) NaOMe, MeOH, 92%.

Mentions: The azido-alkyne-substituted galactose monomer 7 was synthesised in nine steps starting from known 6-O-propargyl-d-galactopyranose 1,31 as outlined in Scheme 1. Propargyl ether 1 was per-O-benzyolated and converted into the required hemiacetal 3 using a solution of ammonia in methanol-THF. The resulting hemiacetal 3 was treated with trichloroacetonitrile and DBU to obtain the corresponding imidate donor 4, which upon activation with trimethylsilyl trifluoromethanesulfonate (TMSOTf) in the presence of 2-(2-(2-chloroethoxy)ethoxy)ethanol gave chlorinated β-glycoside 5 in a respectable 85% yield for the glycosylation step. In the presence of NaN3 and NaI, the chlorinated β-galactoside 5 was converted into the azido β-galactoside 6 in near quantitative yield.


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)

Synthetic route to azido-alkyne-containing galactose monomer 7. Reagents and conditions: a) BzCl, Py, 81%; b) NH3, MeOH/THF (7:3), 64%; c) Cl3CCN, DBU, CH2Cl2, 85%; d) 2-(2-(2-chloroethoxy)ethoxy)ethanol, TMSOTf, CH2Cl2, 85%; e) NaN3, NaI, DMF, 97%; f) NaOMe, MeOH, 92%.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

sch1: Synthetic route to azido-alkyne-containing galactose monomer 7. Reagents and conditions: a) BzCl, Py, 81%; b) NH3, MeOH/THF (7:3), 64%; c) Cl3CCN, DBU, CH2Cl2, 85%; d) 2-(2-(2-chloroethoxy)ethoxy)ethanol, TMSOTf, CH2Cl2, 85%; e) NaN3, NaI, DMF, 97%; f) NaOMe, MeOH, 92%.
Mentions: The azido-alkyne-substituted galactose monomer 7 was synthesised in nine steps starting from known 6-O-propargyl-d-galactopyranose 1,31 as outlined in Scheme 1. Propargyl ether 1 was per-O-benzyolated and converted into the required hemiacetal 3 using a solution of ammonia in methanol-THF. The resulting hemiacetal 3 was treated with trichloroacetonitrile and DBU to obtain the corresponding imidate donor 4, which upon activation with trimethylsilyl trifluoromethanesulfonate (TMSOTf) in the presence of 2-(2-(2-chloroethoxy)ethoxy)ethanol gave chlorinated β-glycoside 5 in a respectable 85% yield for the glycosylation step. In the presence of NaN3 and NaI, the chlorinated β-galactoside 5 was converted into the azido β-galactoside 6 in near quantitative yield.

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.