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
› Author AffiliationsThis 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.
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.
5
Corsello SM,
Bittker JA,
Liu Z,
Gould J,
McCarren P,
Hirschman JE,
Johnston SE,
Vrcic A,
Wong B,
Khan M,
Asiedu J,
Narayan R,
Mader CC,
Subramanian A,
Golub TR.
Nat. Med. 2017; 23: 405
6
Dvela-Levitt M,
Kost-Alimova M,
Emani M,
Kohnert E,
Thompson R,
Sidhom EH,
Rivadeneira A,
Sahakian N,
Roignot J,
Papagregoriou G,
Montesinos MS,
Clark AR,
McKinney D,
Gutierrez J,
Roth M,
Ronco L,
Elonga E,
Carter TA,
Gnirke A,
Melanson M,
Hartland K,
Wieder N,
Hsu JC,
Deltas C,
Hughey R,
Bleyer AJ,
Kmoch S,
Živná M,
Barešova V,
Kota S,
Schlondorff J,
Heiman M,
Alper SL,
Wagner F,
Weins A,
Golub TR,
Lander ES,
Greka A.
Cell 2019; 178: 521-535.e23
