A General Synthesis of Iminosugars

McDonnell, Ciaran; Cronin, Linda; O'Brien, Julie L.; Murphy, Paul V.

doi:10.1021/jo035763u

Cited by 54 publications

(14 citation statements)

References 27 publications

(26 reference statements)

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“…Inhibition of a-glucosidase Our previous study had shown that the triazole derivative 2 was a more potent inhibitor of the a-glucosidase from Bacillus stearothermophilus than 1-deoxynojirimycin 1 [For the synthesis of 1 and DNJ see (5,13,14)]. The alkyne-containing derivatives 3-5, structural analogues of 2, had been prepared as intermediates during the synthesis of 2 and related compounds.…”

Section: Resultsmentioning

confidence: 99%

Biological study of the Angiogenesis Inhibitor N‐(8‐(3‐ethynylphenoxy)octyl‐1‐deoxynojirimycin

2010

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The a-glucosidase inhibitors N-methyl-1-deoxynojirimycin (MDNJ) and castanospermine have been shown to inhibit angiogenesis. A hybrid of 1-deoxynojirimycin (DNJ) and an aryl-1,2,3-triazole, which inhibits both an a-glucosidase and methionine aminopeptidase-2 (MetAP2), displayed properties associated with inhibition of angiogenesis (Bioorg. Med. Chem., 16, 2008, 6333-7). The biological evaluation of a structural analogue N-(8-(3-ethynylphenoxy)octyl-1-deoxynojirimycin is described herein. Although this alkyne derivative did not inhibit MetAP2, it inhibited a bacterial a-glucosidase, altered bovine aortic endothelial cell (BAEC) surface oligosaccharide expression and inhibited BAEC proliferation by inducing G1 phase cell cycle arrest. Experiments showed G1 arrest was attributable to the a-glucosidase inhibitor inducing an increase in p27Kip1 expression and high phosphorylation of ERK1 ⁄ 2 without a reduction in cyclin D1. The DNJ derivative (0.1 mM) prevented capillary tube formation from bovine aortic endothelial cells, whereas DNJ or other analogues were unable to inhibit tube formation at the same concentration. Stress fiber assembly in bovine aortic endothelial cells was abolished, and BAEC migration was inhibited indicating the inhibition of tube formation by this derivative is partially a result of a reduction in cell motility. The agent also caused a reduction in secretion of MMP-2 from bovine aortic endothelial cells. Therefore, the new a-glucosidase inhibitor has a different mechanism by which it inhibits angiogenesis in vitro when compared with deoxynojirimycin, the deoxynojirimycin -triazole hybrid, N-methyl-1-deoxynojirimycin and castanospermine.

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Section: Resultsmentioning

confidence: 99%

Biological study of the Angiogenesis Inhibitor N‐(8‐(3‐ethynylphenoxy)octyl‐1‐deoxynojirimycin

2010

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“…Allyl C-galactopyranoside (1a), [28] Cmannopyranoside (1b), [28] C-glucopyranoside (1c), [28] and 2-acetamido-2-deoxy-C-glucopyranoside (1d), [29] galactose derived alkene 6, [30] and the methylene exo-glycals 8 [31] and 10 [32] were prepared as previously reported. 1 H NMR (300 and 400 MHz), 13 C NMR (75 and 100 MHz), and 31 P NMR (127 and 162 MHz) spectra were recorded in CDCl 3 solutions at room temperature unless otherwise specified.…”

Section: Methodsmentioning

confidence: 99%

Efficiency of the Free‐Radical Hydrophosphonylation of Alkenes: The Photoinduced Reaction of Dimethyl H‐Phosphonate with Enopyranoses as an Exemplary Case

2013

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Free‐radical hydrophosphonylation of alkenes by H‐phosphonates has been reported by other groups to occur under harsh conditions. On the other hand, we demonstrate in this paper that the hydrophosphonylation of alkene functionalized carbohydrates (enopyranoses) by dimethyl H‐phosphonate can be carried out with high efficiency under neutral conditions at room temperature and with short reaction times using UV/Vis light irradiation in the presence of a suitable photoinitiator. Indeed, a range of structurally different allyl C‐glycosides and exo‐glycals were transformed into the corresponding glycosylalkyl phosphonates that were isolated in excellent yields (88–98 %), except for one case (45 %). A mechanism similar to that of the free‐radical photoinduced hydrothiolation of alkenes is proposed.

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“…A catalytic reductive cascade reaction from 5 led to the formation of 6 (Scheme 1). [31] This approach was used in a general synthesis of iminosugars, [32] and this has included the development of a synthesis of castanospermine and 1-epicastanospermine. [33] Scheme 1.…”

Section: Synthesis Of Non-peptide Peptidomimeticsmentioning

confidence: 99%

Peptidomimetics, Glycomimetics and Scaffolds from Carbohydrate Building Blocks

Murphy

2007

Eur J Org Chem

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Saccharides, due to their high density of functional groups and availability as chiral building blocks are scaffolds for bioactive compound discovery. Pyranosides and iminosugar‐based peptidomimetics have been synthesised as ligands for somatostatin receptors and HIV protease. The synthesis of polyhydroxylated macrolides related to natural products and cyclophanes has been achieved from carbohydrate fragments with a view to investigation of their potential as scaffolds. In addition, the trajectory of aromatic systems grafted to saccharides have been studied and this has led to the synthesis of probes for the study of carbohydrate protein interactions. These compounds include geometrically diverse bivalent glycomimetics derived from scaffolds that are hybrids of sugars and aromatic groups. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

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A General Synthesis of Iminosugars

Cited by 54 publications

References 27 publications

Biological study of the Angiogenesis Inhibitor N‐(8‐(3‐ethynylphenoxy)octyl‐1‐deoxynojirimycin

Biological study of the Angiogenesis Inhibitor N‐(8‐(3‐ethynylphenoxy)octyl‐1‐deoxynojirimycin

Efficiency of the Free‐Radical Hydrophosphonylation of Alkenes: The Photoinduced Reaction of Dimethyl H‐Phosphonate with Enopyranoses as an Exemplary Case

Peptidomimetics, Glycomimetics and Scaffolds from Carbohydrate Building Blocks

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