33557-28-7Relevant articles and documents
Molecular recognition in the P2Y14 receptor: Probing the structurally permissive terminal sugar moiety of uridine-5′-diphosphoglucose
Ko, Hyojin,Das, Arijit,Carter, Rhonda L.,Fricks, Ingrid P.,Zhou, Yixing,Ivanov, Andrei A.,Melman, Artem,Joshi, Bhalchandra V.,Kovac, Pavol,Hajduch, Jan,Kirk, Kenneth L.,Harden, T. Kendall,Jacobson, Kenneth A.
experimental part, p. 5298 - 5311 (2009/12/04)
The P2Y14 receptor, a nucleotide signaling protein, is activated by uridine-5′-diphosphoglucose 1 and other uracil nucleotides. We have determined that the glucose moiety of 1 is the most structurally permissive region for designing analogues of this P2Y14 agonist. For example, the carboxylate group of uridine-5′-diphosphoglucuronic acid proved to be suitable for flexible substitution by chain extension through an amide linkage. Functionalized congeners containing terminal 2-acylaminoethylamides prepared by this strategy retained P2Y14 activity, and molecular modeling predicted close proximity of this chain to the second extracellular loop of the receptor. In addition, replacement of glucose with other sugars did not diminish P2Y14 potency. For example, the [5′′]ribose derivative had an EC50 of 0.24 μM. Selective monofluorination of the glucose moiety indicated a role for the 2′′- and 6′′-hydroxyl groups of 1 in receptor recognition. The β-glucoside was twofold less potent than the native α-isomer, but methylene replacement of the 1′′-oxygen abolished activity. Replacement of the ribose ring system with cyclopentyl or rigid bicyclo[3.1.0]hexane groups abolished activity. Uridine-5′-diphosphoglucose also activates the P2Y2 receptor, but the 2-thio analogue and several of the potent modified-glucose analogues were P2Y14-selective.
Selective synthesis of fluorinated carbohydrates using N,N-diethyl-α, α-difluoro-(m-methylbenzyl)amine
Kobayashi, Shingo,Yoneda, Atushi,Fukuhara, Tsuyoshi,Hara, Shoji
, p. 1287 - 1289 (2007/10/03)
Deoxyfluorination of a hydroxy group in carbohydrates was carried out using N,N-diethyl-α,α-difluoro-(m-methylbenzyl)amine. A primary hydroxy group in carbohydrates was effectively converted to the corresponding fluoride under microwave irradiation or at 100°C. Deoxyfluorination of hydroxy groups at the anomeric position proceeded at below room temperature, and glycosyl fluorides could be obtained in good yields. The reaction chemoselectively proceeded, and various protecting groups of carbohydrates can survive under the reaction conditions.
Deoxyfluorination of alcohols using N,N-diethyl-α,α-difluoro- (m-methylbenzyl)amine
Kobayashi, Shingo,Yoneda, Atushi,Fukuhara, Tsuyoshi,Hara, Shoji
, p. 6923 - 6930 (2007/10/03)
Deoxyfluorination of alcohols was carried out using N,N-diethyl-α, α-difluoro-(m-methylbenzyl)amine (DFMBA). Primary alcohols were effectively converted to fluorides under microwave irradiation or conventional heating. Deoxyfluorination of an anomeric hydroxy group in sugars by DFMBA proceeded at below room temperature and glycosyl fluorides could be obtained in good yields. The deoxyfluorination reaction chemoselectively proceeded and various protecting groups on the sugar can survive under the reaction conditions.
