β-Mannosidase and β-hexosaminidase inhibitors: synthesis of 1,2-bis-epi-valienamine and 1-epi-2-acetamido-2-deoxy-valienamine from d-mannose

Ramstadius, Clinton; Hekmat, Omid; Eriksson, Lars; Stålbrand, Henrik; Cumpstey, Ian

doi:10.1016/j.tetasy.2009.02.016

Cited by 20 publications

(5 citation statements)

References 57 publications

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“…1,2-Bisepi-valienamine 153 acts as a -mannosidase [321] inhibitor whereas 2-acetamido-2-deoxy-1-epi-valienamine 154 has been shown [322] to inhibit various -hexosaminidases, enzymes involved in the hydrolysis of terminal N-acetyl-D-hexosamine residues in N-acetyl--D-hexosaminides [323][324][325].…”

Section: International Journal Of Carbohydrate Chemistrymentioning

confidence: 99%

Biosynthesis and Biological Activity of Carbasugars

Roscales

Plumet

2016

International Journal of Carbohydrate Chemistry

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The first synthesis of carbasugars, compounds in which the ring oxygen of a monosaccharide had been replaced by a methylene moiety, was described in 1966 by Professor G. E. McCasland's group. Seven years later, the first true natural carbasugar (5a-carba-R-D-galactopyranose) was isolated from a fermentation broth of Streptomyces sp. MA-4145. In the following decades, the chemistry and biology of carbasugars have been extensively studied. Most of these compounds show interesting biological properties, especially enzymatic inhibitory activities, and, in consequence, an important number of analogues have also been prepared in the search for improved biological activities. The aim of this review is to give coverage on the progress made in two important aspects of these compounds: the elucidation of their biosynthesis and the consideration of their biological properties, including the extensively studied carbapyranoses as well as the much less studied carbafuranoses.

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Section: International Journal Of Carbohydrate Chemistrymentioning

confidence: 99%

Biosynthesis and Biological Activity of Carbasugars

Roscales

Plumet

2016

International Journal of Carbohydrate Chemistry

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“…Few studies have been reported for amination reactions of cyclopropylmethylcarbocation. ,, The reason for that could be the limited range of amine nucleophiles compatible with acidic conditions typically used to initiate the reaction. Previously, we as well as others have demonstrated that bis-imidates are convenient systems for amination of carbocations. In bis-imidates, one of the imidates serves as the leaving group when activated with an acid catalyst while the other acts as an N- nucleophile.…”

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confidence: 90%

Tetrahydro-1,3-oxazepines via Intramolecular Amination of Cyclopropylmethyl Cation

2015

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An efficient synthesis of tetrahydro-1,3-oxazepines was developed involving the regioselective intramolecular amination of cyclopropylmethyl cation. The cation was generated by the abstraction of one imidate group in bis-imidate bearing a carbocation-stabilizing substituent. Using 1,1,2,3-tetrasubstituted cyclopropane substrates, highly diastereoselective intramolecular amination to trans-tetrahydro-1,3-oxazepines was achieved. The resulting tetrahydro-1,3-oxazepines were transformed to the homoallylamine derivatives in high yields.

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“…Valienamine ( 7), an essential unit in many commercial glucosidase inhibitors such as 6 and acarbose, is a potent inhibitor itself. Other closely related aminosugars such as trehazolin (8) (Liebl et al, 2010;El Nemr and El Ashry, 2011) and kirkamide (9) (Sieber et al, 2020) share similar abilities to inhibit Treh, while the C6 epimer of valienamine, epi-valienamine is an inhibitor for various hexosaminidases (Scaffidi et al, 2007) and mannosidases (Ramstadius et al, 2009). The latter has potential as a therapeutic treatment for Gaucher disease (Lin et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…The leaving groups were introduced toward the end using a nucleophilic aromatic substitution (Beenakker et al, 2017). Compounds 3, 4, 5, and 6 and their derivatives have been synthesized by various groups (Knapp et al, 1992;Kapferer et al, 1999;Scaffidi et al, 2007) using similar approaches starting with glucose or mannose scaffolds (Ramstadius et al, 2009). Oligosaccharides such as adiposins (4) and acarbose (Ogawa et al, 1985;Shibata and Ogawa, 1989) have been obtained using common glycosylation methods (Mcauliffe et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of C7/C8-cyclitols and C7N-aminocyclitols from maltose and X-ray crystal structure of Streptomyces coelicolor GlgEI V279S in a complex with an amylostatin GXG–like derivative

Thanvi

Jayasinghe²,

Kapil³

et al. 2022

Front. Chem.

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C7/C8-cyclitols and C7N-aminocyclitols find applications in the pharmaceutical sector as α-glucosidase inhibitors and in the agricultural sector as fungicides and insecticides. In this study, we identified C7/C8-cyclitols and C7N-aminocyclitols as potential inhibitors of Streptomyces coelicolor (Sco) GlgEI-V279S based on the docking scores. The protein and the ligand (targets 11, 12, and 13) were prepared, the states were generated at pH 7.0 ± 2.0, and the ligands were docked into the active sites of the receptor via Glide™. The synthetic route to these targets was similar to our previously reported route used to obtain 4-⍺-glucoside of valienamine (AGV), except the protecting group for target 12 was a p-bromobenzyl (PBB) ether to preserve the alkene upon deprotection. While compounds 11–13 did not inhibit Sco GlgEI-V279S at the concentrations evaluated, an X-ray crystal structure of the Sco GlgE1-V279S/13 complex was solved to a resolution of 2.73 Å. This structure allowed assessment differences and commonality with our previously reported inhibitors and was useful for identifying enzyme–compound interactions that may be important for future inhibitor development. The Asp 394 nucleophile formed a bidentate hydrogen bond interaction with the exocyclic oxygen atoms (C(3)-OH and C(7)-OH) similar to the observed interactions with the Sco GlgEI-V279S in a complex with AGV (PDB:7MGY). In addition, the data suggest replacing the cyclohexyl group with more isosteric and hydrogen bond–donating groups to increase binding interactions in the + 1 binding site.

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β-Mannosidase and β-hexosaminidase inhibitors: synthesis of 1,2-bis-epi-valienamine and 1-epi-2-acetamido-2-deoxy-valienamine from d-mannose

Cited by 20 publications

References 57 publications

Biosynthesis and Biological Activity of Carbasugars

Biosynthesis and Biological Activity of Carbasugars

Tetrahydro-1,3-oxazepines via Intramolecular Amination of Cyclopropylmethyl Cation

Synthesis of C7/C8-cyclitols and C7N-aminocyclitols from maltose and X-ray crystal structure of Streptomyces coelicolor GlgEI V279S in a complex with an amylostatin GXG–like derivative

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