Design, synthesis and glycosidase inhibition of C-4 branched LAB and DAB derivatives

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

“…The combined organic layers were washed with brine, dried over MgSO 4 , concentrated in vacuo, and then purified by flash column chromatography (silica gel, petroleum ether/EtOAc 15 : 1) to afford compound 20 as a light yellow syrup (4.47 g, 10.1 mmol, 73% yield). Data for 20: [α] (21). A solution of compound 20 (1.12 g, 2.5 mmol) in MeOH (100 mL) at −60 °C was bubbled with O 3 until the solution became pale blue.…”

“…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. 9 The two series of C-4 modified derivatives of DAB (10, 11, 13 and 14) not only help understand the interaction modes of DAB derivatives with the corresponding enzymes, but also unveiled the potential of realizing more possibilities with further C-4 structural modifications (Fig.…”

Design and synthesis of iso-allo-DNJ and l-isoDALDP derivatives: pursuit of potent and selective inhibitors of α-glucosidase

“…2,3 Many other iminosugar derivatives, including N -substitution, C -branched, C -nucleoside, 1-azasugars and fluorinated iminosugars, have also found great potential in therapeutic applications concerning diabetes, cancer, viral infection and metabolic disorders associated with their potent glycosidase inhibitions. 3–5…”

Multivalent Pyrrolidine Iminosugars: Synthesis and Biological Relevance

“…For example, 2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine (DMDP, Figure 1 ), the first pyrrolidine iminosugar extracted from the leaves of Derris elliptica in 1976 [ 22 ], proved to be a potent glycosidase inhibitor; subsequently, its analogs were also found to have significant effects on glycosidases [ 23 , 24 , 25 ]. 1,4-Dideoxy-1,4-imino- d -arabinitol (DAB, Figure 1 ), isolated from the fruit of Angylocalyx boutiqueanus , exhibited strong inhibition of glycogen phosphorylase, and is currently being explored for the treatment of type II diabetes [ 26 , 27 ]. 1,4-Dideoxy-1,4-imino- l -arabinitol (LAB, Figure 1 ), the enantiomer of DAB, displayed more potent specific glycosidase inhibition.…”

“…1,4-Dideoxy-1,4-imino- l -arabinitol (LAB, Figure 1 ), the enantiomer of DAB, displayed more potent specific glycosidase inhibition. 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 ].…”