Halogenated d-xylono-δ-lactams: synthesis and enzyme inhibition study

Bhuma, Naresh; Vangala, Madhuri; Nair, Roopa J.; Sabharwal, Sushma G.; Dhavale, Dilip D.

doi:10.1016/j.carres.2014.10.023

Cited by 12 publications

(5 citation statements)

References 47 publications

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“…3-Oxo-α- d -glucofuranose 1 was converted to 2 as per reported protocol. , Treatment of 2 with KF and HCl·H 2 N-Val-OMe, using DBU in t -BuOH afforded 3-( S )-fluoro-Val-OMe 3 in 52% yield (Scheme ). Deprotection of 5,6-acetonide functionality with 60% AcOH afforded a 5,6-diol 4 that on treatment with NaIO 4 , followed by reaction with NaBH 4 , afforded alcohol 5 .…”

Section: Resultsmentioning

confidence: 99%

Acyclic αγα-Tripeptides with Fluorinated- and Nonfluorinated-Furanoid Sugar Framework: Importance of Fluoro Substituent in Reverse-Turn Induced Self-Assembly and Transmembrane Ion-Transport Activity

et al. 2017

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Acyclic αγα-tripeptides derived from fluorinated-furanoid sugar amino acid frameworks act as reverse-turn inducers with a U-shaped conformation, whereas the corresponding nonfluorinated αγα-tripeptides show random peptide conformations. The NMR studies showed the presence of bifurcated weak intramolecular hydrogen bonding (F···HN) and N···F charge-dipole attraction compel the amide carbonyl groups to orient antiperiplanar to the C-F bond, thus, demonstrating the role of the fluorine substituent in stabilizing the U-shaped conformation. The NOESY data indicate that the U-shaped tripeptides self-assembly formation is stabilized by the intermolecular hydrogen bonding between C═O···HN with antiparallel orientation. This fact is supported by ESI-MS data, which showed mass peaks up to the pentameric self-assembly, even in the gas phase. The morphological analysis by FE-SEM, on solid samples, showed arrangement of fibers into nanorods. The antiparallel self-assembled pore of the fluorinated tripeptides illustrates the selective ion-transport activity. The experimental findings were supported by DFT studies.

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Section: Resultsmentioning

confidence: 99%

Acyclic αγα-Tripeptides with Fluorinated- and Nonfluorinated-Furanoid Sugar Framework: Importance of Fluoro Substituent in Reverse-Turn Induced Self-Assembly and Transmembrane Ion-Transport Activity

et al. 2017

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“…Targeting towards the synthesis of spiro-bislactams, the azido compound 15 was treated with TFA-H 2 O (5 : 1) at 0 C to rt for 24 h that afforded g-d-spiro-[5.4]-bis-lactam 3 as a white solid in 87% yield. This reaction involves in situ hydrolysis of the 1,2-acetonide functionality and the concomitant Schmidt-Boyer rearrangement 21 to give 3 in one pot. The 1 H-NMR spectrum of compound 3 showed 9a as doublet of doublet with coupling constants of 12.0 and 10.0 Hz while; 9e showed doublet of doublet with coupling constants of 12.0 and 6.0 Hz.…”

Section: Resultsmentioning

confidence: 99%

Diazaspiro-iminosugars and polyhydroxylated spiro-bislactams: synthesis, glycosidase inhibition and molecular docking studies

et al. 2015

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Synthesis of a new class of iminosugars 1-4 has been reported. The Jocic-Reeve and Corey-Link approach with a-D-glucofuranos-3-ulose 5 afforded 3-azidoaldehyde 7 that was converted to the g-lactam 9.Reductive aminocyclisation and Schmidt-Boyer reactions were used to get spiro-iminosugars 1-4 which showed selective and potent glycosidase inhibitory activities. Molecular docking studies support the activity data.

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“…For example, castanospermine IIa is known to be an immunosuppressive agent, while replacement of C-1 hydroxyl functionality in IIa with hydroxymethyl substituent having (1 S ) IIb and (1 R ) IIc configuration showed significant immunostimulating properties by up-regulation of T H1 /T H2 cytokine ratio (IL-6 and IL-4) with their excellent cell proliferating activity without showing any inhibition toward the glycosidase enzymes . In the continuation of our interest in this area, we now report synthesis of hitherto unknown quaternary indolizidines 1a , 2a , 3a and indolizidone iminosugars 1b , 1c , 2b , and 3b (Figure ), wherein hydroxymethyl group is present at the ring junction C8a. These castanospermine analogues showed good immunopotentiating activity as compared to the parent castanospermine IIa as well as moderate to potent glycosidase inhibitory activity against various enzymes under study.…”

Section: Introductionmentioning

confidence: 90%

Quaternary Indolizidine and Indolizidone Iminosugars as Potential Immunostimulating and Glycosidase Inhibitory Agents: Synthesis, Conformational Analysis, Biological Activity, and Molecular Docking Study

et al. 2015

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New quaternary indolizidine iminosugars, with hydroxymethyl group at the ring junction, namely, C-8a-hydroxymethyl-1-deoxycastanospermine congeners 1a, 2a, 3a and their 3-oxo analogs 1b, 2b, and 3b were synthesized by using intramolecular reductive aminocyclization/lactamization of d-mannose/D-glucose derived C5-γ-azido esters as a key step wherein both the rings of the indolizidine skeleton were built up in one pot following the cascade reaction pathway. The conformations ((5)C8 or (8)C5) of 1-3 were assigned on the basis of the (1)H NMR studies. All compounds were found to be potent inhibitors of various glycosidase enzymes with Ki and IC50 values in the micromolar/nanomolar concentration range and further substantiated by molecular docking studies. The effect of synthesized iminosugars 1-3 on the cytokine secretion of IL-4, IL-6, and IFN-γ was evaluated. All compounds were found to be TH1 bias increasing the TH1/TH2 cytokines ratio (IL-6 and IL-4) indicating their potency as immunostimulating agents. Our study suggests that immunomodulatory activity of indolizidine iminosugars can be tuned by minor structural/stereochemical alterations.

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Halogenated d-xylono-δ-lactams: synthesis and enzyme inhibition study

Cited by 12 publications

References 47 publications

Acyclic αγα-Tripeptides with Fluorinated- and Nonfluorinated-Furanoid Sugar Framework: Importance of Fluoro Substituent in Reverse-Turn Induced Self-Assembly and Transmembrane Ion-Transport Activity

Acyclic αγα-Tripeptides with Fluorinated- and Nonfluorinated-Furanoid Sugar Framework: Importance of Fluoro Substituent in Reverse-Turn Induced Self-Assembly and Transmembrane Ion-Transport Activity

Diazaspiro-iminosugars and polyhydroxylated spiro-bislactams: synthesis, glycosidase inhibition and molecular docking studies

Quaternary Indolizidine and Indolizidone Iminosugars as Potential Immunostimulating and Glycosidase Inhibitory Agents: Synthesis, Conformational Analysis, Biological Activity, and Molecular Docking Study

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