Journal article
Tyler A. Davis, A. Vilgelm, A. Richmond, J. N. Johnston
2014
2014
Semantic Scholar
DOI
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APA
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Davis, T. A., Vilgelm, A., Richmond, A., & Johnston, J. N. (2014). Preparation of (‐)‐Nutlin‐3 Using Enantioselective Organocatalysis at Decagram Scale.
Chicago/Turabian
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Davis, Tyler A., A. Vilgelm, A. Richmond, and J. N. Johnston. “Preparation of (‐)‐Nutlin‐3 Using Enantioselective Organocatalysis at Decagram Scale.” (2014).
MLA
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Davis, Tyler A., et al. Preparation of (‐)‐Nutlin‐3 Using Enantioselective Organocatalysis at Decagram Scale. 2014.
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@article{tyler2014a,
title = {Preparation of (‐)‐Nutlin‐3 Using Enantioselective Organocatalysis at Decagram Scale.},
year = {2014},
author = {Davis, Tyler A. and Vilgelm, A. and Richmond, A. and Johnston, J. N.}
}
Abstract
Chiral nonracemic cis-4,5-bis(aryl)imidazolines have emerged as a powerful platform for the development of cancer chemotherapeutics, stimulated by the Hoffmann-La Roche discovery that Nutlin-3 can restore apoptosis in cells with wild-type p53. The lack of efficient methods for the enantioselective synthesis of cis-imidazolines, however, has limited their more general use. Our disclosure of the first enantioselective synthesis of (−)-Nutlin-3 provided a basis to prepare larger amounts of this tool used widely in cancer biology. Key to the decagram-scale synthesis described here was the discovery of a novel bis(amidine) organocatalyst that provides high enantioselectivity at warmer reaction temperature (−20 °C) and low catalyst loadings. Further refinements to the procedure led to the synthesis of (−)-Nutlin-3 in a 17 g batch and elimination of all but three chromatographic purifications.
