The Development of an Aza-C-Glycoside Library Based on a Tandem Staudinger/Aza-Wittig/Ugi Three-Component Reaction

T. Wennekes; K.M. Bonger; K. Vogel; S.A. van den Berg; A. Strijland; W.E. Donker-Koopman; J. Aerts; A. van der Marel; H.S. Overkleeft

doi:10.1002/ejoc.201200923

The Development of an Aza-C-Glycoside Library Based on a Tandem Staudinger/Aza-Wittig/Ugi Three-Component Reaction

T. Wennekes, K.M. Bonger, K. Vogel, S.A. van den Berg, A. Strijland, W.E. Donker-Koopman, J. Aerts, A. van der Marel, H.S. Overkleeft

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

We report the tandem Staudinger/aza-Wittig/Ugi three-component reaction mediated synthesis of a 64-member compound library of aza-C-glycosides. The library is composed of four pyrrolidine and three piperidine scaffolds, onto which a number of functional groups is grafted to form seven sublibraries. Variation in the library is achieved by transformation of two pentoses and a hexose into the corresponding 4-azidopentanal and 5-azidohexanal derivatives as precursors for the Staudinger/aza-Wittig process. Further variation is achieved by using different isocyanides as well as protective- and functional-group manipulations on the fully protected Ugi-3CR intermediates. Preliminary biological evaluation of the compound library revealed several low micromolar inhibitors of human acid glucosylceramidase

Original language	English
Pages (from-to)	6420-6454
Journal	European Journal of Organic Chemistry
Volume	2012
Issue number	32
DOIs	https://doi.org/10.1002/ejoc.201200923
Publication status	Published - 2012

Keywords

ugi 4-component condensation
gaucher-disease
multicomponent reactions
nonlysosomal glucosylceramidase
functionalized pyrrolidines
pharmacological chaperones
n-butyldeoxynojirimycin
combinatorial libraries
bicyclic scaffolds
storage disorders

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10.1002/ejoc.201200923

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Wennekes, T., Bonger, K. M., Vogel, K., van den Berg, S. A., Strijland, A., Donker-Koopman, W. E., Aerts, J., van der Marel, A., & Overkleeft, H. S. (2012). The Development of an Aza-C-Glycoside Library Based on a Tandem Staudinger/Aza-Wittig/Ugi Three-Component Reaction. European Journal of Organic Chemistry, 2012(32), 6420-6454. https://doi.org/10.1002/ejoc.201200923

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title = "The Development of an Aza-C-Glycoside Library Based on a Tandem Staudinger/Aza-Wittig/Ugi Three-Component Reaction",

abstract = "We report the tandem Staudinger/aza-Wittig/Ugi three-component reaction mediated synthesis of a 64-member compound library of aza-C-glycosides. The library is composed of four pyrrolidine and three piperidine scaffolds, onto which a number of functional groups is grafted to form seven sublibraries. Variation in the library is achieved by transformation of two pentoses and a hexose into the corresponding 4-azidopentanal and 5-azidohexanal derivatives as precursors for the Staudinger/aza-Wittig process. Further variation is achieved by using different isocyanides as well as protective- and functional-group manipulations on the fully protected Ugi-3CR intermediates. Preliminary biological evaluation of the compound library revealed several low micromolar inhibitors of human acid glucosylceramidase",

keywords = "ugi 4-component condensation, gaucher-disease, multicomponent reactions, nonlysosomal glucosylceramidase, functionalized pyrrolidines, pharmacological chaperones, n-butyldeoxynojirimycin, combinatorial libraries, bicyclic scaffolds, storage disorders",

author = "T. Wennekes and K.M. Bonger and K. Vogel and {van den Berg}, S.A. and A. Strijland and W.E. Donker-Koopman and J. Aerts and {van der Marel}, A. and H.S. Overkleeft",

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AU - Vogel, K.

AU - van den Berg, S.A.

AU - Strijland, A.

AU - Donker-Koopman, W.E.

AU - Aerts, J.

AU - van der Marel, A.

AU - Overkleeft, H.S.

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AB - We report the tandem Staudinger/aza-Wittig/Ugi three-component reaction mediated synthesis of a 64-member compound library of aza-C-glycosides. The library is composed of four pyrrolidine and three piperidine scaffolds, onto which a number of functional groups is grafted to form seven sublibraries. Variation in the library is achieved by transformation of two pentoses and a hexose into the corresponding 4-azidopentanal and 5-azidohexanal derivatives as precursors for the Staudinger/aza-Wittig process. Further variation is achieved by using different isocyanides as well as protective- and functional-group manipulations on the fully protected Ugi-3CR intermediates. Preliminary biological evaluation of the compound library revealed several low micromolar inhibitors of human acid glucosylceramidase

KW - ugi 4-component condensation

KW - gaucher-disease

KW - multicomponent reactions

KW - nonlysosomal glucosylceramidase

KW - functionalized pyrrolidines

KW - pharmacological chaperones

KW - n-butyldeoxynojirimycin

KW - combinatorial libraries

KW - bicyclic scaffolds

KW - storage disorders

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DO - 10.1002/ejoc.201200923

M3 - Article

SN - 1434-193X

VL - 2012

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JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

IS - 32

ER -

The Development of an Aza-C-Glycoside Library Based on a Tandem Staudinger/Aza-Wittig/Ugi Three-Component Reaction

Abstract

Keywords

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