Generation of a Heteropolycyclic and sp3-Rich Scaffold for Library Synthesis from a Highly Diastereoselective Petasis/Diels–Alder and ROM–RCM Reaction Sequence

Thomas Flagstad; Carlos M.G. Azevedo; Nikolaj S. Troelsen; Geanna K. Min; Yohan Macé; Anthony Willaume; Rachel Guilleux; Mélanie Velay; Karine Bonnet; Remy Morgentin; Thomas E. Nielsen; Mads H. Clausen

doi:10.1002/ejoc.201801551

Generation of a Heteropolycyclic and sp³-Rich Scaffold for Library Synthesis from a Highly Diastereoselective Petasis/Diels–Alder and ROM–RCM Reaction Sequence

Thomas Flagstad, Carlos M.G. Azevedo, Nikolaj S. Troelsen, Geanna K. Min, Yohan Macé, Anthony Willaume, Rachel Guilleux, Mélanie Velay, Karine Bonnet, Remy Morgentin, Thomas E. Nielsen^*, Mads H. Clausen

^*Corresponding author for this work

2 Citations (Scopus)

Abstract

Efficient access to diverse screening compounds with desirable, lead-like properties can be a bottleneck in early drug discovery and chemical biology. Herein we present an efficient, rapid route to three structurally distinct classes of compounds (A–C) from a single precursor, which in turn is available through a one-pot Petasis 3-component reaction/Diels–Alder cascade reaction. We demonstrate the versatility of the approach through the synthesis of 35 exemplary compounds from the three classes, as well as by the production of 2188 final compounds, which have been included in the Joint European Compound Library of the European Lead Factory.

Original language	English
Journal	European Journal of Organic Chemistry
Volume	2019
Issue number	5
Pages (from-to)	1061-1076
ISSN	1434-193X
DOIs	https://doi.org/10.1002/ejoc.201801551
Publication status	Published - 7 Feb 2019

Keywords

Cycloaddition
Drug discovery
Heterocycles
Library synthesis

Access to Document

10.1002/ejoc.201801551

Cite this

Flagstad, T., Azevedo, C. M. G., Troelsen, N. S., Min, G. K., Macé, Y., Willaume, A., Guilleux, R., Velay, M., Bonnet, K., Morgentin, R., Nielsen, T. E., & Clausen, M. H. (2019). Generation of a Heteropolycyclic and sp³-Rich Scaffold for Library Synthesis from a Highly Diastereoselective Petasis/Diels–Alder and ROM–RCM Reaction Sequence. European Journal of Organic Chemistry, 2019(5), 1061-1076. https://doi.org/10.1002/ejoc.201801551

Generation of a Heteropolycyclic and sp³-Rich Scaffold for Library Synthesis from a Highly Diastereoselective Petasis/Diels–Alder and ROM–RCM Reaction Sequence. / Flagstad, Thomas; Azevedo, Carlos M.G.; Troelsen, Nikolaj S. et al.
In: European Journal of Organic Chemistry, Vol. 2019, No. 5, 07.02.2019, p. 1061-1076.

Research output: Contribution to journal › Journal article › Research › peer-review

Flagstad, T, Azevedo, CMG, Troelsen, NS, Min, GK, Macé, Y, Willaume, A, Guilleux, R, Velay, M, Bonnet, K, Morgentin, R, Nielsen, TE & Clausen, MH 2019, 'Generation of a Heteropolycyclic and sp³-Rich Scaffold for Library Synthesis from a Highly Diastereoselective Petasis/Diels–Alder and ROM–RCM Reaction Sequence', European Journal of Organic Chemistry, vol. 2019, no. 5, pp. 1061-1076. https://doi.org/10.1002/ejoc.201801551

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abstract = "Efficient access to diverse screening compounds with desirable, lead-like properties can be a bottleneck in early drug discovery and chemical biology. Herein we present an efficient, rapid route to three structurally distinct classes of compounds (A–C) from a single precursor, which in turn is available through a one-pot Petasis 3-component reaction/Diels–Alder cascade reaction. We demonstrate the versatility of the approach through the synthesis of 35 exemplary compounds from the three classes, as well as by the production of 2188 final compounds, which have been included in the Joint European Compound Library of the European Lead Factory.",

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AU - Azevedo, Carlos M.G.

AU - Troelsen, Nikolaj S.

AU - Min, Geanna K.

AU - Macé, Yohan

AU - Willaume, Anthony

AU - Guilleux, Rachel

AU - Velay, Mélanie

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