85026-59-1Relevant articles and documents
Synthesis of 4a-Carba-d-lyxofuranose Derivatives and Their Evaluation as Inhibitors of GH38 α-Mannosidases
Zaji?ková, Mária,Monco?, Ján,?esták, Sergej,Kóňa, Juraj,Koó?, Miroslav,Bella, Maro?
, p. 1114 - 1124 (2019/01/24)
A synthetic approach to 4a-carba-d-lyxofuranose derivatives starting from d-lyxose is described. The protected 4a-carba-β-d-lyxofuranose was employed as the key intermediate for the synthesis of 4a-carba-d-lyxofuranose derivatives including novel 1-amino-1-deoxy-4a-carba-d-lyxofuranoses. Synthesized 4a-carba-d-lyxofuranoses were evaluated as inhibitors of GH38 α-mannosidases, namely, the Golgi (GMIIb) and lysosomal (LManII) α-mannosidases from Drosophila melanogaster and commercial Jack bean α-mannosidase (JBMan) from Canavalia ensiformis. The biochemical evaluation revealed that only 1-amino-1-deoxy-4a-carba-β-d-lyxofuranose exhibited reasonable inhibitory activity against GMIIb (IC50 = 200 μm). In addition, the results of biological evaluation were discussed by means of molecular modelling.
Synthesis of carba-NAD and the structures of its ternary complexes with SIRT3 and SIRT5
Szczepankiewicz, Bruce G.,Dai, Han,Koppetsch, Karsten J.,Qian, Dongming,Jiang, Fan,Mao, Cheney,Perni, Robert B.
, p. 7319 - 7329 (2012/11/13)
Carba-NAD is a synthetic compound identical to NAD except for one substitution, where an oxygen atom adjacent to the anomeric linkage bearing nicotinamide is replaced with a methylene group. Because it is inert in nicotinamide displacement reactions, carba-NAD is an unreactive substrate analogue for NAD-consuming enzymes. SIRT3 and SIRT5 are NAD-consuming enzymes that are potential therapeutic targets for the treatment of metabolic diseases and cancers. We report an improved carba-NAD synthesis, including a pyrophosphate coupling method that proceeds in approximately 60% yield. We also disclose the X-ray crystal structures of the ternary complexes of SIRT3 and SIRT5 bound to a peptide substrate and carba-NAD. These X-ray crystal structures provide critical snapshots of the mechanism by which human sirtuins function as protein deacylation catalysts.
Variable strategy toward carbasugars and relatives. 4. Viable access to (4a-carbapentofuranosyl)amines, (5a-carbahexopyranosyl)amines, and amino acids thereof
Rassu, Gloria,Auzzas, Luciana,Pinna, Luigi,Zambrano, Vincenzo,Zanardi, Franca,Battistini, Lucia,Marzocchi, Lucia,Acquotti, Domenico,Casiraghi, Giovanni
, p. 5338 - 5342 (2007/10/03)
A chiral, divergent synthesis of two carbafuranosylamines, 1 and 2, two carbapyranosylamines, 3 and 4, two carbafuranosylamino acids, 5 and 6, and two carbapyranosylamino acids, 7 and 8, has been achieved. Highlights of the procedure include the following: a diastereoselective crossed vinylogous Mukaiyama aldol coupling between N-(tert-butoxycarbonyl)-2-[(tert-butyldimethylsilyl)-oxy]pyrrole (TBSOP, 9) and 2,3-O-isopropylidene-D-glyceraldehyde (10) for the assembly of the target compound carbon backbone; a high-yielding silylative cycloaldolization that gives the cyclopentanoid and cyclohexanoid motifs; and a reductive or hydrolytic breakage of the lactam C(O)-N link to liberate the carbasugar and install the desired pseudo-anomeric amine and the hydroxymethyl or carboxyl functionalities. The sequences leading to trans-configured carbafuranosyl compounds 1 and 5 and carbapyranosyl compounds 3 and 7 were 12- and 13-step processes, with overall yields of 34%, 35%, 17%, and 16%. Cis-configured isomers 2, 4, 6, and 8 were obtained only in minor yields.