An efficient synthesis of D-galactose-based multivalent neoglycoconjugates

Abstract

Este trabalho descreve a síntese de neoglicoconjugados diméricos, triméricos e tetraméricos derivados de D-galactose. O ligante monossacarídico foi preparado em cinco etapas utilizando-se a modificação de Doebner da reação de Knoevenagel na etapa de extensão da cadeia lateral. O ligante foi acoplado a 1,4-butanodiamina, tris-(2-etilamino)amina, pentaeritritiltetramina e dendrímeros PAMAM (núcleo 1,4-butanodiamina G0 e núcleo 1,12-dodecanodiamina G0). Os glicodendrímeros desprotegidos foram purificados por cromatografia por exclusão de tamanho (SEC). Esta foi a única etapa em que um método cromatográfico foi empregado em toda rota sintética. Essa é uma estratégia nova e eficiente para a preparação de neoglicoconjugados.In this work, the synthesis of dimeric, trimeric and tetrameric D-galactose-based neoglycoconjugates is reported. The monosaccharide ligand was prepared in 5 straightforward steps from D-galactose using the Doebner modification of the Knoevenagel reaction for chain elongation. The ligand was coupled to 1,4-butanediamine, tris-(2-ethylamino)amine, pentaerythrityltetramine and PAMAM dendrimers (1,4-butanodiamine core G0 and 1,12-dodecanediamine core G0). The unprotected glycodendrimers were purified by size-exclusion chromatography (SEC). This was the only step in which a chromatographic method was employed throughout the synthetic route. This is a new and efficient strategy for the preparation of neoglycoconjugates.

Synthesis of Galectin Inhibitors by Regioselective 3′-O-Sulfation of Vanillin Lactosides Obtained under Phase Transfer Catalysis

“…NMR COSY and HSQC experiments were also used to unambiguously correlate the sulfation process and regioselectivity. A Knoevenagel-Doebner condensation was also used (malonic acid, C5H5N, Piperidine, 95° C, 3h) for the synthesis of two carbons homologated vanillin lactosides 17-20 (Scheme 3), analogously used before for a galactoside derivative [48]. Thus, aldehyde 5 provided peracetylated α, β-unsaturated analog 17 in 65% yield, which upon catalytic hydrogenation (H2, Pd-C, THF-MeOH, rt, 5 h) gave the expected α, β-saturated lactoside 19 essentially quantitatively.…”

Synthesis of a novel series of 2,3,4-trisubstituted oxazolidines designed by isosteric replacement or rigidification of the structure and cytotoxic evaluation

“…29 An initial attempt to couple 20 with 4-nitroaniline to give 5 was carried out using NHS and EDC. 30 Unfortunately, this mild and useful method did not lead to product formation. We believe that delocalization of the nonbonding electron pair in 4-nitroaniline results in low nucleophilicity.…”

Alkylation of Galactosyl, Mannosyl and Lactosyl Barbiturate

“…Finally, bromo acetamide was investigated as electrophile in the alkylation of galactose barbiturate. The amide bond is one of the most useful connections to attach a carbohydrate moiety to a core or dendrimer (de Andrade et al, 2012). As a simple test, the N-benzyl bromoacetamide was used as the electrophile.…”

“…physicochemical properties compared to the high molecular weight, multivalent ones (de Andrade et al, 2012).…”