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; Rjbhn van den Berg; A. Strijland; W. E. Donker-Koopman; Johannes M F G Aerts; G. 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, Rjbhn van den Berg, A. Strijland, W. E. Donker-Koopman, Johannes M F G Aerts, G. A. van der Marel, H. S. Overkleeft^*

^*Corresponding author for this work

Leiden University

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

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
Externally published	Yes

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Wennekes, T., Bonger, K. M., Vogel, K., van den Berg, R., Strijland, A., Donker-Koopman, W. E., Aerts, J. M. F. G., van der Marel, G. 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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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.",

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

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doi = "10.1002/ejoc.201200923",

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AU - Wennekes, T.

AU - Bonger, K. M.

AU - Vogel, K.

AU - van den Berg, Rjbhn

AU - Strijland, A.

AU - Donker-Koopman, W. E.

AU - Aerts, Johannes M F G

AU - van der Marel, G. A.

AU - Overkleeft, H. S.

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N2 - 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.

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.

U2 - 10.1002/ejoc.201200923

DO - 10.1002/ejoc.201200923

M3 - Article

SN - 0075-4617

VL - 2012

SP - 6420

EP - 6454

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

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