Synthesis of Glycosyl Derivatives as Dopamine Prodrugs: Interaction with Glucose Carrier GLUT‐1.

Abstract

Carbohydrates Carbohydrates U 0500 Synthesis of Glycosyl Derivatives as Dopamine Prodrugs: Interaction with Glucose Carrier GLUT-1. -(FERNANDEZ, C.; NIETO, O.; FONTENLA, J. A.; RIVAS, E.; DE CEBALLOS, M. L.; FERNANDEZ-MAYORALAS*, A.; Org.

Studies on the Uptake of Glucose Derivatives by Red Blood Cells

“…After incubation of 30 (15 mm) with erythrocytes under similar conditions as above, the glucose conjugate was detected in lysates in an amount similar to that obtained with the C6 substituted regioisomer 6 (0.5 mmol mL À1 for 30 versus 0.8 mmol mL À1 for 6). In our previous work, [16] we showed that the substitution of glucose at the anomeric position leads to compounds with low or no binding to GLUT-1; therefore, the uptake of 30 seems to support a mechanism of penetration different from the use of the GLUT-1 transporter. 1 H MAS NMR spectra corresponding to samples of a) erythrocytes, and erythrocytes incubated with b) 2, c) 3, d) 5, e) 6, and f) 8.…”

“…Although compounds 2, 3, 5, or 6 must bind to the glucose carrier, being analogous in structure to other C6 modified glucoses that showed high affinity for GLUT-1, [16] it seems that the subsequent translocation from membrane bound to cytoplasm, which is the rate-limiting step, should be precluded from occurring.…”

“…Compound 2 was obtained by alkylation of partially benzylated glucose derivative 9 [16] with 3-phenylpropyl bromide to give 10, which was submitted to debenzylation (Scheme 2). The synthesis of carbamates 3-7 was carried out by coupling the 6-O-imidazolylcarbonyl glucose derivative 11 [16] with the corresponding amine 12-16 to give conjugates 17-21, followed by hydrogenolysis (Scheme 2). For 21, the phenolic hydroxyl groups were acetylated (22) before removal of the benzyl groups.…”

“…[15][16] A variety of glycoconjugates with dopamine attached by ester, carbamate, and glycosidic bonds to different O-positions in the glucose were synthesized, and their affinity for the glucose carrier GLUT-1 using human erythrocytes was evaluated. Except for the glucose derivatives substituted at position C6, all other modifications of the sugar gave compounds with low or no binding to the carrier.…”

Synthesis, characterization andin vitroevaluation of substitutedN-(2-phenylcyclopropyl)carbamates as acetyl- and butyrylcholinesterase inhibitors

“…The preparation of such designed carbamates was inspired by the hypothesis that they can possess a high level of transport ability [59][60][61] over blood-brain barrier via GLUT-family sugar/ polyol transport facilitators 62 . Better transport of the active molecules can then lead to their enhanced concentration in intracellular space of CNS.…”