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

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

a   Center for the Development of Therapeutics, Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA
,
Brian T. Chamberlain
a   Center for the Development of Therapeutics, Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA
,
Isabelle Chataigner
b   Sorbonne Université, CNRS, Laboratoire de Chimie Théorique, LCT, 75005 Paris, France
c   Normandie Université, UNIROUEN, CNRS, INSA Rouen, COBRA Laboratory, 76000 Rouen, France
,
Riccardo Spezia
b   Sorbonne Université, CNRS, Laboratoire de Chimie Théorique, LCT, 75005 Paris, France
,
Florence F. Wagner
a   Center for the Development of Therapeutics, Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA
› Institutsangaben
This work was funded by the Slim Initiative for Genomic Medicine in the Americas (SIGMA), a collaboration of the Broad Institute with the Carlos Slim Foundation.


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.

Supporting Information



Publikationsverlauf

Eingereicht: 14. Dezember 2022

Angenommen nach Revision: 19. Januar 2023

Accepted Manuscript online:
19. Januar 2023

Artikel online veröffentlicht:
20. März 2023

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