title: Chemo-enzymatic synthesis and glycosidase inhibitory properties of DAB and LAB derivatives.
abstract: A chemo-enzymatic strategy for the preparation of 2-aminomethyl derivatives of (2R,3R,4R)-2-(hydroxymethyl)pyrrolidine-3,4-diol (also called 1,4-dideoxy-1,4-imino-D-arabinitol, DAB) and its enantiomer LAB is presented. The synthesis is based on the enzymatic preparation of DAB and LAB followed by the chemical modification of their hydroxymethyl functionality to afford diverse 2-aminomethyl derivatives. This strategy leads to novel aromatic, aminoalcohol and 2-oxopiperazine DAB and LAB derivatives. The compounds were preliminarily explored as inhibitors of a panel of commercial glycosidases, rat intestinal disaccharidases and against Mycobacterium tuberculosis, the causative agent of tuberculosis. It was found that the inhibitory profile of the new products differed considerably from the parent DAB and LAB. Furthermore, some of them were active inhibiting the growth of M. tuberculosis.
authors: Dept Química Biológica y Modelización Molecular, Instituto de Química Avanzada de Cataluña, IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain.
authors: Alda Lisa
authors: AL
authors: Concia
authors: Livia
authors: L
authors: Gómez
authors: Jordi
authors: J
authors: Bujons
authors: Teodor
authors: T
authors: Parella
authors: Cristina
authors: C
authors: Vilaplana
authors: Pere Joan
authors: PJ
authors: Cardona
authors: Jesús
authors: J
authors: Joglar
authors: Pere
authors: P
authors: Clapés
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001089:Arabinose / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004186:Disaccharidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D050113:Imino Furanoses / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D051381:Rats; D013329:Structure-Activity Relationship; D013402:Sugar Alcohols / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D050113:Imino Furanoses; D013402:Sugar Alcohols; C058137:1,4-dideoxy-1,4-iminoarabinitol; D001089:Arabinose; D004186:Disaccharidases; D006026:Glycoside Hydrolases