Hexafluoroisopropanol-Induced Facial Selectivity in a Hindered Diels–Alder Reaction

David J. P. Kornfilt; Brian T. Chamberlain; Isabelle Chataigner; Riccardo Spezia; Florence F. Wagner

doi:10.1055/a-2016-4548

Synthesis, Table of Contents

Synthesis 2023; 55(13): 2047-2052
DOI: 10.1055/a-2016-4548

paper

Hexafluoroisopropanol-Induced Facial Selectivity in a Hindered Diels–Alder Reaction

David J. P. Kornfilt ‡

^aCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA

,

Brian T. Chamberlain‡

^aCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA

,

Isabelle Chataigner

^bSorbonne Université, CNRS, Laboratoire de Chimie Théorique, LCT, 75005 Paris, France

^cNormandie Université, UNIROUEN, CNRS, INSA Rouen, COBRA Laboratory, 76000 Rouen, France

,

Riccardo Spezia

^bSorbonne Université, CNRS, Laboratoire de Chimie Théorique, LCT, 75005 Paris, France

,

Florence F. Wagner∗

^aCenter for the Development of Therapeutics, Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA

› Author Affiliations

Abstract

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Abstract

BRD4780 is a small molecule that can selectively clear mutant MUC1-fs protein in mucin kidney disease models. Prior syntheses of BRD4780 were unsuitable for preparation on large scale. In this manuscript, HFIP is described as a unique solvent that allowed the key Diels–Alder reaction to proceed with >20:1 endo diastereoselectivity, enabling the kg-scale preparation of BRD4780 for further studies.

Key words

Diels–Alder reaction - nitroalkene - BRD4780 - mucin-1 kidney disease - HFIP

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References

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