Novel and Efficient Chemoenzymatic Synthesis of D‐Glucose 6‐Phosphate and Molecular Modeling Studies on the Selective Biocatalysis

Abstract

Abstract:A concise chemoenzymatic synthesis of glucose-6-phosphate is described. Candida rugosa lipase was found to be an efficient catalyst for both regio-and stereoselective deacetylation of the primary hydroxyl group in the peracetylated D-glucose. In addition, we report an improved synthesis of 1,2,3,4,6-penta-O-acetyl--D-glucopyranose providing a large-scale procedure for the acetylation of -D-glucose without isomerization at the anomeric center. The high overall yield and the easy scalability makes this chemoenzymatic strategy attractive for industrial application. Furthermore, molecular modeling of phosphonate transition-state analogue for the enzymatic hydrolysis step supports the substrate selectivity observed with Candida rugosa lipase.

Chemoenzymatic Syntheses and Anti-HIV-1 Activity of Glucose−Nucleoside Conjugates as Prodrugs

“…Commercial Candida rugosa lipase (CRL) was found to be an efficient catalyst for both regio- and chemoselective deacetylation of the primary hydroxyl group in the peracetylated α-D-glucose, furnishing the 6-OH derivative 6 in excellent yield after crystallization from diethyl ether/ n -hexane (4:1) (29). The synthesis of the phosphoramidite 7 was carried out by phosphitylation of 6 with 2-cyanoethyl- N,N,N′,N′ -tetraisopropyl phosphoramidite and pyridinium trifluoroacetate as activator in high yield (31).…”

Regioselective C‐6 Hydrolysis of MethylO‐Benzoyl‐pyranosides Catalysed byCandida RugosaLipase

“…This parallels the activity observed for various lipases towards other acetylated carbohydrates. [23,24] A challenge in hydrolysis of benzoylated pyranosides is their low solubility in water, causing mass-transfer limitations and rate retardation. Therefore the hydrolytic activity of CRL towards 3c was examined in the presence of acetone, THF, dioxane and 2-propanol.…”

“…[19] As opposed to standard methods, regioselective hydrolysis catalysed by enzymes offers a two step route. [20][21][22][23][24] Candida rugosa lipase (CRL) has proven to be the catalyst of choice for deacetylation at C-6. [20,24] The lipase has a rather wide active site and the ability to tolerate high concentrations of organic co-solvents.…”

“…[20][21][22][23][24] Candida rugosa lipase (CRL) has proven to be the catalyst of choice for deacetylation at C-6. [20,24] The lipase has a rather wide active site and the ability to tolerate high concentrations of organic co-solvents. [25][26][27] The hydrolysis of glucose pentaacetate has been investigated at different pH by several authors.…”

“…[25][26][27] The hydrolysis of glucose pentaacetate has been investigated at different pH by several authors. [20,23,24] Reactions at pH 4-5 using CRL led to high regioselectivity favouring hydrolysis at C-6, whereas at methyl 2,3,4,6-tetra-O-benzoyl-β-D-galactopyranoside substrate inhibition were observed, which in part could be overcome by increasing the reaction volume. Methyl 2,3,4,6-tetra-O-benzoyl-β-D-glucopyranoside and methyl 2,3,4,6-tetra-O-benzoyl-α-D-mannopyranoside were poor substrates for Candida rugosa lipase and low degree of conversion towards products were obtained under all conditions.…”