Chemo-enzymatic synthesis and glycosidase inhibitory properties of DAB and LAB derivatives.

  title={Chemo-enzymatic synthesis and glycosidase inhibitory properties of DAB and LAB derivatives.},
  author={Alda Lisa Concia and L. G{\'o}mez and J. Bujons and T. Parella and C. Vilaplana and P. Cardona and J. Joglar and P. Clap{\'e}s},
  journal={Organic \& biomolecular chemistry},
  volume={11 12},
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… Expand
Inhibitory properties of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) derivatives acting on glycogen metabolising enzymes.
Results are consistent with a model in which these compounds bind to the subsite in the active centre of the enzymes that is normally occupied by the glucosyl residue which is transferred between donor and acceptor substrates. Expand
A common strategy towards the synthesis of 1,4-dideoxy-1,4-imino-l-xylitol, deacetyl (+)-anisomycin and amino-substituted piperidine iminosugars.
A strategy towards the synthesis of three different target molecules, namely 1,4-dideoxy-1, 4-imino-l-xylitol, deacetyl (+)-anisomycin and amino-substituted piperidine iminosugars, is reported from a common amino-vicinal diol intermediate derived from tri-O-benzyl-d-glucal. Expand
Casuarine stereoisomers from achiral substrates: chemoenzymatic synthesis and inhibitory properties.
The new ent-3-epi-casuarine is a strong inhibitor of α-d-glucosidase from rice and of rat intestinal sucrase and its enantiomer DAB and LAB were obtained from dihydroxyacetone and aminoethanol using D-fructose-6-phosphate aldolase and L-rhamnulose-1-ph phosphate a Aldolase catalysts, respectively. Expand
Inhibitor versus chaperone behaviour of d-fagomine, DAB and LAB sp(2)-iminosugar conjugates against glycosidases: A structure-activity relationship study in Gaucher fibroblasts.
A library of sp(2)-iminosugar conjugates derived from the piperidine iminosugar d-fagomine and the enantiomeric pyrrolidine iminougars DAB and LAB is generated, showing an unfavourable chaperone/inhibitor balance on disease-associated GCase mutants in cellulo. Expand
Expedient synthesis of C-aryl carbohydrates by consecutive biocatalytic benzoin and aldol reactions.
An expedient asymmetric "de novo" synthetic route to new aryl carbohydrate derivatives based on two sequential stereoselectively biocatalytic carboligation reactions is presented. Expand
Strategy for designing selective α-l-rhamnosidase inhibitors: Synthesis and biological evaluation of l-DMDP cyclic isothioureas.
These new mimics of l-rhamnose may affect other enzymes associated with the biochemistry of rhamnosed including enzymes involved in progression of tuberculosis. Expand
C-branched iminosugars: α-glucosidase inhibition by enantiomers of isoDMDP, isoDGDP, and isoDAB-L-isoDMDP compared to miglitol and miglustat.
L-IsoDMDP, prepared in 11 steps in an overall yield of 45% from d-lyxonolactone, is a potent specific competitive inhibitor of gut disaccharidases and is more effective in the suppression of hyperglycaemia in a maltose loading test than miglitol, a drug presently used in the treatment of late onset diabetes. Expand
l-Rhamnulose-1-phosphate and l-fuculose-1-phosphate aldolase mediated multi-enzyme cascade systems for nitrocyclitol synthesis
Abstract One-pot multistep stereoselective cascade reactions were implemented for the straightforward synthesis of various nitrocyclitols. Two kinases, an aldolase and a phosphatase were involved inExpand
Recent Developments in the Preparation of Carbohydrate Derivatives from Achiral Building Blocks by using Aldolases
The central role of carbohydrates in medicinal chemistry has stimulated intensive research in the last few years to develop simpler and more efficient routes for their preparation. Among them, routesExpand
Fructose-6-phosphate aldolases as versatile biocatalysts for nitrocyclitol syntheses
Efficient and stereoselective polyhydroxylated nitrocyclitol syntheses were performed via biocatalysed aldol reactions. The key step was based on a one-pot/one-enzyme cascade reaction process whereExpand


Synthesis and glycosidase inhibitory activities of 2-(aminoalkyl)pyrrolidine-3,4-diol derivatives.
Several 2-(aminomethyl)-and 2-(2-aminoethyl)-pyrrolidine-3,4-diol derivatives have been assayed for their inhibitory activities towards glycosidases. Good inhibitors of alpha-mannosidases must haveExpand
Effect of five-membered sugar mimics on mammalian glycogen-degrading enzymes and various glucosidases.
Salacinol showed a much more potent inhibitory activity toward maltase in Caco-2 cell model system than its de-sulfonated derivative, and was further a stronger inhibitor of human lysosomal alpha-glucosidase than the derivative, which indicates that the sulfate in the side chain plays an important role in the specificity of enzyme inhibition. Expand
Syntheses and Glycosidase Inhibitory Activities of 2‐(Aminomethyl)‐5‐(hydroxymethyl)pyrrolidine‐3,4‐diol Derivatives
New 2-(aminomethyl)-5-(hydroxymethyl)pyrrolidine-3,4-diol derivatives were synthesized from (5S)-5-[(trityloxy)methyl]pyrrolidin-2-one (6) (Schemes 1 and 2) and their inhibitory activities toward 25Expand
Efficient synthesis from d-lyxonolactone of 2-acetamido-1,4-imino-1,2,4-trideoxy-l-arabinitol LABNAc, a potent pyrrolidine inhibitor of hexosaminidases
The synthesis from d-lyxonolactone of 2-acetamido-1,4-imino-1,2,4-trideoxy-l-arabinitol LABNAc proceeded in an overall yield of 25%; the enantiomer, 2-acetamido-1,4-imino-1,2,4-trideoxy-d-arabinitolExpand
α-Rhamnosidase inhibitory activities of polyhydroxylated pyrrolidine
Abstract We designed and synthesized polyhydroxylated pyrrolidines 1 – 12 from l -tyrosine, l -phenylalanine, and d -tyrosine through iodine-mediated intramolecular cyclization followed byExpand
Functionalized pyrrolidines inhibit alpha-mannosidase activity and growth of human glioblastoma and melanoma cells.
Functionalized pyrrolidines have the potential to inhibit the growth of tumor cells and display selectivity for tumor cells when compared to normal cells. Expand
Nitrogen-in-the-ring pyranoses and furanoses: structural basis of inhibition of mammalian glycosidases.
Investigation of the contribution of epimerization, deoxygenation, and conformation to the potency of inhibition and specificity of mammalian glycosidases suggests that it superimposes well on the various glycosyl cations. Expand
Kinetic and functional characterization of 1,4-dideoxy-1, 4-imino-d-arabinitol: a potent inhibitor of glycogen phosphorylase with anti-hyperglyceamic effect in ob/ob mice.
DAB inhibited the hepatic glycogen breakdown in vivo and displayed an accompanying anti-hyperglycemic effect, which was most pronounced in obese mice, suggesting that inhibition of GP may offer a therapeutic principle in Type 2 diabetes. Expand
Occurrence of the alpha-glucosidase inhibitor 1,4-Dideoxy-1,4-imino-D-arabinitol and related iminopentitols in marine sponges.
This is the first report on the isolation and detection of 1 and 2 in marine invertebrates and the least active or inactive extracts showed no detectable imino pentitols. Expand
Dihydroxyacetone phosphate aldolase catalyzed synthesis of structurally diverse polyhydroxylated pyrrolidine derivatives and evaluation of their glycosidase inhibitory properties.
Molecular models of aldol products with iPr and iBu substituents and as complexes with the RhuA active site suggest that the anti adducts could be kinetically preferred, while the syn adductions would be the equilibrium products. Expand