General synthesis and biological evaluation of α-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-α-C-glycosides)

Goujon, Jean-Yves; Gueyrard, David; Compain, Philippe; Martin, Olivier R.; Ikeda, Kyoko; Kato, Atsushi; Asano, Naoki

doi:10.1016/j.bmc.2004.12.043

Cited by 38 publications

(18 citation statements)

References 64 publications

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“…These com-pounds binding at the catalytic site can be regarded as oxocarbenium ion mimics. A "C-glycosyl" derivative of fagomine (Entry 4) showed no inhibition towards RMGPb [107], while a seven membered iminosugar analog (Entry 5) also had no effect on RMGPb [108]. In summary, most efficient inhibitors of the catalytic site can be found among N-acyl-N'--D-glucopyranosyl ureas, Nand C--D-glucopyranosyl heterocycles, and some iminosugars (especially DAB).…”

Section: Iminosugarsmentioning

confidence: 95%

New Inhibitors of Glycogen Phosphorylase as Potential Antidiabetic Agents

Somsák

Czifrák

Tóth

et al. 2008

CMC

141

132

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The protein glycogen phosphorylase has been linked to type 2 diabetes, indicating the importance of this target to human health. Hence, the search for potent and selective inhibitors of this enzyme, which may lead to antihyperglycaemic drugs, has received particular attention. Glycogen phosphorylase is a typical allosteric protein with five different ligand binding sites, thus offering multiple opportunities for modulation of enzyme activity. The present survey is focused on recent new molecules, potential inhibitors of the enzyme. The biological activity can be modified by these molecules through direct binding, allosteric effects or other structural changes. Progress in our understanding of the mechanism of action of these inhibitors has been made by the determination of high-resolution enzyme inhibitor structures (both muscle and liver). The knowledge of the three-dimensional structures of protein-ligand complexes allows analysis of how the ligands interact with the target and has the potential to facilitate structure-based drug design. In this review, the synthesis, structure determination and computational studies of the most recent inhibitors of glycogen phosphorylase at the different binding sites are presented and analyzed.

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Section: Iminosugarsmentioning

confidence: 95%

New Inhibitors of Glycogen Phosphorylase as Potential Antidiabetic Agents

Somsák

Czifrák

Tóth

et al. 2008

CMC

141

132

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“…93 Iminosugar-based aziridine 88 was found to be a versatile intermediate for the synthesis of fagomine C-glycoside derivatives. 58 The ring-opening of bicyclic aziridine 88 with various heteroatomic nucleophiles including thiols, amines, alcohols, carboxylates, and phosphates occurred in modest to very good yields and was found to be completely regioselective (Scheme 63).…”

Section: Iminosugar C-glycoside Building Blocksmentioning

confidence: 98%

“…55 A loss of diastereoselectivity is observed in the absence of an alkoxy group at C-3, as judged by the cyclization of 3-deoxy heptenitol 53 (Scheme 32). 58 Ganem et al utilized a cyclization promoted by mercury(II) salts to form the C5-N bond in iminosugar C-glycosides 55 and 57 (Scheme 33). 59 In this case, the degree of stereoselectivity was found to be strongly dependent on the configuration at C-1 of the starting material.…”

Section: Electrophile-induced Cyclization Of Aminoalkenesmentioning

confidence: 99%

Tactics and strategies for the synthesis of iminosugar C-glycosides: a review

Compain

Chagnault

Martin

2009

Tetrahedron: Asymmetry

Self Cite

160

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“…Piperidine 1,2‐dideoxy‐azasugars represent a small but important niche in the fields of azasugar chemistry and azasugar bioactivity 1b,7b,11. Thus, 1,2,5‐trideoxy‐1,5‐imino‐ D ‐arabinitol ( I ) (fagomine in Figure 1) was first isolated in 1974 from buckwheat seeds14 and recently was found to have a potent antihyperglycemic effect in streptozocin‐induced diabetic mice and to potentiate markedly immunoreactive insulin release 15.…”

Section: Introductionmentioning

confidence: 99%

Glycals in Organic Synthesis: A Systematic Strategy for the Preparation of Uncommon Piperidine 1,2‐Dideoxy‐L‐azasugars and 2‐Deoxy‐1,5‐anhydro‐L‐hexitols

et al. 2007

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A systematic synthetic strategy has been developed for producing uncommon piperidine 1,2-dideoxy-L-azasugars. This method involves the formation of open intermediates such as 2, 7, and 10 easily by ring-opening of D-glycals with aqueous mercury(II) acetate/sodium borohydride. A concise sequence of regioselective amination and cyclization reactions then allowed us to prepare the cyclic compounds 5a and 5b, L enantiomers of naturally occurring fagomine congeners such as 3-epi-fagomine (II) and 3,4-di-epi-fagomine (III), from Dglucal and D-galactal, respectively. The unnatural 3,4-di-epi-6-deoxyfagomine 9 was obtained from L-rhamnal by the

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General synthesis and biological evaluation of α-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-α-C-glycosides)

Cited by 38 publications

References 64 publications

New Inhibitors of Glycogen Phosphorylase as Potential Antidiabetic Agents

New Inhibitors of Glycogen Phosphorylase as Potential Antidiabetic Agents

Tactics and strategies for the synthesis of iminosugar C-glycosides: a review

Glycals in Organic Synthesis: A Systematic Strategy for the Preparation of Uncommon Piperidine 1,2‐Dideoxy‐L‐azasugars and 2‐Deoxy‐1,5‐anhydro‐L‐hexitols

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