Fluorinated Radicamine A and B: Synthesis and Glycosidase Inhibition

Abstract

Fluorinated derivatives of radicamine A and radicamine B have been synthesized from D-arabinose-derived cyclic nitrone. Structure-activity relationship studies showed that glycosidase inhibition of these fluorinated derivatives was sig-

Design, synthesis and glycosidase inhibition of DAB derivatives with C-4 peptide and dipeptide branches

“…4.4.1 (2R,3R,4R)-2,3-Bis(benzyloxy)-1-hydroxy-4-vinyl-pyrrolidine (19). To a solution of D-tartrate-derived nitrone 18 (4.46 g, 15.0 mmol) in dry THF (30 mL) was injected vinyl magnesium bromide (1.0 M in THF, 30.0 mL, 30.0 mmol) at 0 °C and stirred at room temperature for 2 h. After TLC showed completion of the conversion, the reaction was quenched with saturated aqueous NH 4 Cl (30 mL), diluted with water (50 mL), and extracted with EtOAc (3 × 30 mL).…”

“…For example, the α- C -1-alkyl-DABs ( 2 ) with long alkyl chains exhibited potent and selective inhibition against human β-glucocerebrosidase, 13 and broussonetines 3–6 which feature 13-carbon long chains containing various functional groups are potent β-glucosidase, β-galactosidase and β-mannosidase inhibitors. 14,15 While the introduction of an additional N -acetylaminomethyl group endowed compound 7 with potent and selective inhibition of β-HexNAcases, 16,17 the α-C-1-(hetero)aryl-DABs, such as radicamine A ( 8 ) 18 and imino- C -nucleoside 9 , showed potent and selective inhibition of α-glucosidase 19 and human purine nucleoside phosphorylase, 20 respectively. When the modification strategy was applied at the C-4 position, compounds 10–13 showed potent and specific α-glucosidase inhibition, 21 whereas the C-4 hydroxymethyl depleted C -arylated DABs 14 were powerful and selective human β-glucocerebrosidase inhibitors.…”

Stereoselective Production of Imino‐d‐ribitol and C‐Azanucleosides through Electrochemical C−H Functionalization

“…Furthermore, acidic cleavage conditions for the resulting N ‐hydroxy moiety (e. g. excess zinc and AcOH) induced anomeric epimerization which gave a diastereomeric mixture of α‐ and β‐anomers. Although hydrogenation using a Pd/C catalyst is a mild method for this use, [4f] the reduction‐sensitive functionalities, such as halogen or nitro substituents, are incompatible.…”

“…Some iminosugars possess strong inhibitory activity against various enzymes. For example, nojirimycin [2a–c] and radicamines A and B [2d–e] were found to be glycosidase inhibitors, and their derivatives have been developed as pharmaceutical candidates for diabetes treatment (Figure 1A).…”

Multivalent Pyrrolidine Iminosugars: Synthesis and Biological Relevance

“…A new α-glucosidase inhibitor based on LAB was reported by Kato et al in 2012, which showed huge potential in reducing elevated plasma glucose after food intake when tested in vivo with a carbohydrate load at doses approximately ten times lower than the required dose of miglitol [ 27 , 28 , 29 , 30 ]. In addition, Radicamines A and B have attracted extensive interest because of their potent inhibition of α-glucosidases and potential pharmaceutical applications [ 31 , 32 , 33 ]. Overall, ample evidence has established that iminosugars have anti-diabetic effects [ 34 , 35 , 36 , 37 , 38 ].…”