Creation of quaternary stereocentres: synthesis of new polyhydroxylated indolizidines

Langlois, Nicole; Nguyen, Bao Khanh Le; Retailleau, Pascal; Tarnus, Céline; Salomon, Emmanuel

doi:10.1016/j.tetasy.2005.11.017

Cited by 21 publications

(6 citation statements)

References 22 publications

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“…20 The bridgehead hydroxymethyl salts 70 and 71 were weak inhibitors of a-glucosidases (IC 50 0.57 and 0.59 mM, respectively); and 70 also inhibited b-galactosidase (IC 50 0.56 mM). 21 The lactone 72, also a likely precursor of hydroxymethyl variants of castanospermine, was synthesised by methodology involving nitrone cycloadditions, 22 but was not developed further. Finally, the interesting hexahydroxylated perhydroazaazulene 73, a ring homologue of castanospermine, showed 38% and 65% inhibition of bovine liver b-galactosidase and Rhizopus mould amyloglucosidase, respectively, at a concentration of 1 mM.…”

Section: Castanospermine and Related Compoundsmentioning

confidence: 99%

Indolizidine and quinolizidine alkaloids

2008

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This review covers the isolation, structure determination, synthesis, chemical transformations and biological activity of indolizidine and quinolizidine alkaloids. Included in the review are the hydroxylated indolizidines lentiginosine, swainsonine, castanospermine and their analogues; alkaloids from animal sources, including arthropods and amphibians; alkaloids from the genera Polygonatum, Prosopis and Poranthera; phenanthroindolizidine and phenanthroquinolizidine alkaloids; Nuphar alkaloids; lupine alkaloids; and alkaloids from marine sources. 130 references are cited.

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Section: Castanospermine and Related Compoundsmentioning

confidence: 99%

Indolizidine and quinolizidine alkaloids

2008

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“…Thus, reduction of 12 and 13 with alane (AlH 3 ) gave after silica gel purification 1 and 2 in 92% and 95% yield, respectively. 17 This route provides enantiomerically pure 1-azabicyclo[4.3.0]nonane.…”

Section: Resultsmentioning

confidence: 99%

Studies towards the construction of quaternary indolizidines by [2,3]-sigmatropic rearrangement cocatalyzed by ionic liquid

Durán-Lara¹,

Shankaraiah²,

Geraldo³

et al. 2009

J. Braz. Chem. Soc.

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Uma abordagem enantiosseletiva eficiente para a preparação de centros quaternários a partir da prolina 5 foi desenvolvida através do rearranjo [2,3]-sigmatrópico de Stevens, co-catalisado por líquido iônico. O rearranjo sigmatrópico foi estereoespecífico porque as migrações- [2,3] foram restritas à mesma face e a estereosseletividade surgiu na etapa preliminar da N-alquilação em 8. O método mostrou melhores rendimentos do que os descritos na literatura. O uso de hexafluorofostato de 1-butil-3-metilimidazólio mostrou uma melhora nos rendimentos do rearranjo de Stevens devido a possível estabilização e/ou ativação das espécies zuiteriônicas em solução, pelo líquido iônico. Diversas indolizidinas foram sintetizadas a partir do derivado (S)-5 da prolina quaternária.An efficient enantioselective approach for preparation of quaternary centers from proline 5 building block has been developed through [2,3]-sigmatropic Stevens rearrangement co-catalyzed by ionic liquid. The sigmatropic rearrangement was stereospecific because the [2,3]-migrations were restricted to the same face, and the stereoselectivity arose from the previous N-alkylation step in 8. The approach showed better yields than described in literature. The use of 1-butyl-3-methylimidazolium hexafluorophosphate showed an improvement in the yields of the Stevens rearrangement due to a possible stabilization and/or activatation of zwiterionic species in solution by the ionic liquid. Several indolizidine moieties were synthesized from quaternary proline derivative (S)-5.

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“…To achieve this, Langlois et al used methodology that involves nucleophilic addition to N-acyliminium ions followed by ring-closure metathesis. 22 Santos et al used 2,3-sigmatropic rearrangement of (S)-allylproline derivative to construct quaternary stereocenter bearing the nitrogen atom. 23 Recently, we have developed a methodology for the construction of a quaternary carbon, bearing the nitrogen atom and formyl group (chemical equivalent to −CH 2 OH), using the Jocic−Reeve and Corey−Link type reaction with C-5 keto hexoses that leads to the formation of sugar α-azidoaldehyde (A) which gives an access for the synthesis of α-geminal dihydroxymethyl piperdine and pyrrolidine iminosugars.…”

Section: ■ Introductionmentioning

confidence: 99%

“…For example, Liu and Johnson et al synthesized C-5 hydroxymethyl 1-deoxycastanospermine derivative which showed potent α-glucosidase inhibitory activity. Pandey et al reported C-8 hydroxymethyl substituted 1-deoxycastanospermine which showed moderate inhibitory activity against β-glucosidase, while only two reports in which hydroxymethyl group is at the ring junction IVa , b are known so far, from Langlois and Santos groups, which were found to be moderate α-/β-galactosidase inhibitors.…”

Section: Introductionmentioning

confidence: 99%

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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Creation of quaternary stereocentres: synthesis of new polyhydroxylated indolizidines

Cited by 21 publications

References 22 publications

Indolizidine and quinolizidine alkaloids

Indolizidine and quinolizidine alkaloids

Studies towards the construction of quaternary indolizidines by [2,3]-sigmatropic rearrangement cocatalyzed by ionic liquid

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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