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: Alda Lisa Concia, Livia Gómez, Jordi Bujons, Teodor Parella, Cristina Vilaplana, Pere Joan Cardona, Jesús Joglar, Pere Clapés
• Journal: Organic & biomolecular chemistry (Org Biomol Chem) Vol. 11 Issue 12 Pg. 2005-21 (Mar 28 2013) ISSN: 1477-0539 [Electronic] England
• PMID: 23381224 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Enzyme Inhibitors
• Imino Furanoses
• Sugar Alcohols
• 1,4-dideoxy-1,4-iminoarabinitol
• Arabinose
• Disaccharidases
• Glycoside Hydrolases

Topics

• Animals
• Anti-Bacterial Agents (chemistry, metabolism, pharmacology)
• Arabinose (chemistry, metabolism, pharmacology)
• Disaccharidases (antagonists & inhibitors, metabolism)
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (chemistry, metabolism, pharmacology)
• Glycoside Hydrolases (antagonists & inhibitors, chemistry, metabolism)
• Imino Furanoses (chemistry, metabolism, pharmacology)
• Intestinal Mucosa (metabolism)
• Intestines (enzymology)
• Microbial Sensitivity Tests
• Molecular Structure
• Mycobacterium tuberculosis (drug effects, growth & development)
• Rats
• Structure-Activity Relationship
• Sugar Alcohols (chemistry, metabolism, pharmacology)