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Kleban, Martin; Hilgers, Petra; Greul, Jörg N.; Kugler, Rolf; Li, Jing; Picasso, Sylviane; Vogel, Pierre; Jäger, Volker

doi:10.1002/1439-7633(20010504)2:5<365::aid-cbic365>3.3.co;2-d

Cited by 10 publications

(23 citation statements)

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“…8 The synthesis and biological evaluation of a small number of Mannostatin analogs has revealed that the basicity of the primary amine and the neighboring cis-diol are essential for inhibitory activity. [20][21][22][23][24][25][26] While interest in mannostatin A continues to grow, the mode of inhibition of this compound is not well understood. In this respect, its carbocyclic structure represents a significant departure from common alkaloid-based glycosidase inhibitors, and it is unclear whether mannostatin resembles either D-mannose or the mannosyl oxacarbenium ion.…”

Section: Introductionmentioning

confidence: 99%

Structural Basis of the Inhibition of Golgi α-Mannosidase II by Mannostatin A and the Role of the Thiomethyl Moiety in Ligand−Protein Interactions

et al. 2006

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The X-ray crystal structures of mannose trimming enzyme Drosophila Golgi α-mannosidase II (dGMII) complexed with the inhibitors mannostatin A (1) and an N-benzyl analog (2) have been determined. Molecular dynamics simulations and NMR studies have shown that the five-membered ring of mannostatin A is rather flexible occupying pseudo-rotational itineraries between 2 T 3 and 5 E, and 2 T 3 and 4 E. In the bound state, mannostatin A adopts a 2 T 1 twist envelope conformation, which is not significantly populated in solution. Possible conformations of the mannosyl oxacarbenium ion and an enzyme-linked intermediate have been compared to the conformation of mannostatin A in the co-crystal structure with dGMII. It has been found that mannostatin A best mimics the covalent linked mannosyl intermediate, which adopts a 1 S 5 skew boat conformation. The thiomethyl group, which is critical for high affinity, superimposes with the C-6 hydroxyl of the covalent linked intermediate. This functionality is able to make a number of additional polar and non-polar interactions increasing the affinity for dGMII. Furthermore, the X-ray structures show that the environment surrounding the thiomethyl group of 1 is remarkably similar to the arrangements around the methionine residues in the protein. Collectively, our studies contradict the long held view that potent inhibitors of glycosidases mimic an oxacarbenium ion like transition state.

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Section: Introductionmentioning

confidence: 99%

Structural Basis of the Inhibition of Golgi α-Mannosidase II by Mannostatin A and the Role of the Thiomethyl Moiety in Ligand−Protein Interactions

et al. 2006

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“…[23] Iodosugar 6, upon treatment with Zn dust in MeOH in the presence of a catalytic amount of cyanocobalamin at room temperature, yielded cyclic hemiacetal 5 (as an α/β mixture). [24] Its Wittig methylenation with methyltriphenylphosphonium bromide in the presence of tBuOK afforded diene 4 (Scheme 2). Oxidation of the allylic alcohol in 4 was attempted by using oxidizing agents like MnO 2 , PCC, and PDC, but in each case, decomposition of the starting material was mainly observed with formation of the desired product in very poor yield (5-10 %).…”

Section: Resultsmentioning

confidence: 99%

Diethylaluminum Iodide Promoted Morita–Baylis–Hillman Reaction of D‐Glucose‐Derived Densely O‐Functionalized Cyclopentenone: Route to α‐C‐Branched Densely Functionalized Cyclic Enones

Ghosal¹,

Ajay²,

Bajpai³

et al. 2012

Eur J Org Chem

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Morita–Baylis–Hillman (MBH) reaction of D‐glucose‐derived highly O‐functionalized cyclopentenone is described for the first time. The MBH reaction of cyclopentenone with different aldehydes in the presence of diethylaluminum iodide proceeded smoothly in moderate to good yields. Promoters such as organic, inorganic, or Lewis bases and an aqueous medium are not suitable conditions for the MBH reaction of highly O‐functionalized cyclopentenones with aldehydes.

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“…Although the cyclization of oxime ethers toward the synthesis of aminocyclitols is known in the literature, 15 to the best of our knowledge, the iodocyclization of the sugar derived oxime ethers of type 1c to their corresponding THFs has not yet been reported. Herein, we report the full results of iodocyclization of oximes 4, 5, 6, and 16 to obtain new tetrasubstituted THFs 7a-d, 8a-c, 9a,b, and 17a,b, respectively.…”

Section: Introductionmentioning

confidence: 99%

An iodocyclization approach toward diastereoselective synthesis of highly functionalized tetrasubstituted tetrahydrofurans with 2,5-trans and 2,5-cis relationships from pyranoside derived acyclic oximes

Kumar

Gauniyal

Shaw

2007

Tetrahedron: Asymmetry

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Cited by 10 publications

References 0 publications

Structural Basis of the Inhibition of Golgi α-Mannosidase II by Mannostatin A and the Role of the Thiomethyl Moiety in Ligand−Protein Interactions

Structural Basis of the Inhibition of Golgi α-Mannosidase II by Mannostatin A and the Role of the Thiomethyl Moiety in Ligand−Protein Interactions

Diethylaluminum Iodide Promoted Morita–Baylis–Hillman Reaction of D‐Glucose‐Derived Densely O‐Functionalized Cyclopentenone: Route to α‐C‐Branched Densely Functionalized Cyclic Enones

An iodocyclization approach toward diastereoselective synthesis of highly functionalized tetrasubstituted tetrahydrofurans with 2,5-trans and 2,5-cis relationships from pyranoside derived acyclic oximes

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