1037210-08-4Relevant articles and documents
Development of a Multi Kilogram-Scale, Tandem Cyclopropanation Ring-Expansion Reaction en Route to Hedgehog Antagonist IPI-926
Austad, Brian C.,Hague, Andrew B.,White, Priscilla,Peluso, Stéphane,Nair, Somarajan J.,Depew, Kristopher M.,Grogan, Michael J.,Charette, André B.,Yu, Lin-Chen,Lory, Caroline D.,Grenier, Louis,Lescarbeau, André,Lane, Benjamin S.,Lombardy, Richard,Behnke, Mark L.,Koney, Nii,Porter, James R.,Campbell, Matthew J.,Shaffer, Jeanne,Xiong, Jimin,Helble, Joseph C.,Foley, Michael A.,Adams, Julian,Castro, Alfredo C.,Tremblay, Martin R.
, p. 786 - 798 (2016/05/19)
The formation of the d-homocyclopamine ring system in IPI-926 is the key step in its semisynthesis and proceeds via a chemoselective cyclopropanation followed by a stereoselective acid-catalyzed carbocation rearrangement. In order to perform large-scale cyclopropanation reactions, we developed new iodomethylzinc bis(aryl)phosphate reagents that were found to be both effective and safe. These soluble reagents can be prepared under mild conditions and are stable during the course of the reaction. Importantly, they have favorable energetics relative to other cyclopropanating agents such as EtZnCH2I. Herein, we describe the process optimization studies that led to successful large-scale production of the d-homocyclopamine core necessary for IPI-926.
HETEROCYCLIC CYCLOPAMINE ANALOGS AND METHODS OF USE THEREOF
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Page/Page column 28-29, (2008/12/08)
The present invention relates to steroidal alkaloid-like compounds that can be used in the treatment of hedgehog pathway related disorders, particularly cancer.
