Conformational Effects on Glycoside Reactivity:  Study of the High Reactive Conformer of Glucose

Abstract

The effect of conformation on glycoside reactivity was investigated by studying the hydrolysis of a selection of 3,6-anhydroglucosides as models for glucose in the highly reactive (1)C(4) conformation. Methyl 3,6-anhydro-beta-D-glucopyranoside was found to hydrolyze 200-400 times faster than methyl glucosides in the (4)C(1) conformation, while methyl 3,6-anhydro-beta-D-galactopyranoside, which is in the B(1,4) conformation, was less reactive than methyl beta-D-galactopyranoside. Methyl (3,6-anhydro-beta-D-glucopyranosyl)-(1 --> 6)-alpha-D-glucopyranoside, methyl (3,6-anhydro-alpha-D-glucopyranosyl)-(1 --> 6)-alpha-D-glucopyranosyl-(1 --> 6)-alpha-D-glucopyranoside, and methyl (3,6-anhydro-beta-D-glucopyranosyl)-(1 --> 6)-alpha-D-glucopyranosyl-(1 --> 6)-alpha-D-glucopyranoside were prepared and found to react selectively at the anhydro residue. The finding that (1)C(4) conformers of glucosides are highly reactive species is in accordance with and supports previous results showing that axial OH groups are less electron withdrawing than equatorial OH groups.

Quantifying Electronic Effects of Common Carbohydrate Protecting Groups in a Piperidine Model System

“…Synthesis of 1-deoxynojirimycin followed by protecting group manipulations to give the target compounds 16,19,21,23, and 25. Pyr = pyridine.…”

“…Again 1 H NMR spectroscopy (Table 1) was diagnostic for the conformation, with small coupling constants (smaller than 5 Hz) between the ring protons comparable with those observed in 3,6-anhydroglucoside derivatives. [16] Determination of the base strength: With the target compounds in hand the pK a values were determined by titration using an acetonitrile/water mixture (50 % by mass). The compounds were titrated with NaOH in water with simultaneous addition of equal amounts of acetonitrile (2 burette system).…”

“…This was confirmed in the study of 3,6-anhydrides of glucosides: these molecules hydrolyse 200-400 times faster than glucosides. [16] This led to the idea that forcing conformational change in a glycosyl donor with predominantly equatorial OR groups would lead to superior reactivity. This was indeed the case for axial rich silylated glycosyl donors, which have superior reactivity compared with armed donors.…”

Síntese de beta-N-acetilglicosaminídeos de arila modificados em C-6 como potenciais agentes antimicrobianos

“…Os glicosídeos 5 e 11 foram obtidos a partir de 4 e 10 por reação de transesterificação com metóxido de sódio em metanol 24 , ambos com rendimento quantitativo. A tosilação regiosseletiva de C-6 dos glicosídeos 5 e 11 forneceu os tosilatos correspondentes 6 e 12, com rendimentos de 62 e 76%, respectivamente 25 , os quais, por reação subseqüente com azida de sódio em DMF forneceram os derivados 6-azido correspondentes 7 e 13, com rendimentos de 99 e 94%, respectivamente 26 . As aminas 8 e 14 foram preparadas por hidrogenação catalítica do grupo azido 27 de 7 e 13, com ren-dimentos de 94 e 98%, respectivamente.…”

“…Foram obtidos 0,51 g (0,98 mmol), 76,8% de rendimento a Método geral para a preparação dos glicosídeos 7 e 13 26 A um balão foi adicionado o derivado tosilado 25 6 ou 12 e azida de sódio em DMF anidra. O balão foi acoplado a um condensador de refluxo e a mistura reagente mantida a 60 °C em banho de óleo, com agitação magnética.…”