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Bioactive Indanes: Proof Of Concept Study For Enantioselective Synthetic Routes To Ph46a, A New Potential Anti-Inflammation Agent, Tao Zhang, Gaia Scalabrino, Neil Frankish, Helen Sheridan
Bioactive Indanes: Proof Of Concept Study For Enantioselective Synthetic Routes To Ph46a, A New Potential Anti-Inflammation Agent, Tao Zhang, Gaia Scalabrino, Neil Frankish, Helen Sheridan
Articles
PH46A is a single enantiomer and a member of the 1,2-indane dimer family. It has two contiguous stereogenic centers with S,S configurations, one of which being a quaternary center, which has been developed as a clinical candidate for the treatment of inflammatory and autoimmune conditions. The current synthetic route to PH46A involves the generation of an unwanted enantiomer (R,R)-7, thus reducing the final yield significantly. Therefore, we have investigated potential alternatives to improve the efficiency of this synthesis. The first phase of the study has demonstrated proof of principle for a chiral alkylation of ketone 3 using phase-transfer …
Investigation Of The Stereoselective Synthesis Of The Indane Dimer Ph46a, A New Potential Anti-Inflammatory Agent, Graham R. Cumming, Tao Zhang, Gaia Scalabrino, Neil Frankish, Helen Sheridan
Investigation Of The Stereoselective Synthesis Of The Indane Dimer Ph46a, A New Potential Anti-Inflammatory Agent, Graham R. Cumming, Tao Zhang, Gaia Scalabrino, Neil Frankish, Helen Sheridan
Articles
PH46A, belonging to a class of 1,2-Indane dimers, has been developed by our research group as a potential therapeutic agent for the treatment of inflammatory and autoimmune diseases. The initial synthetic route to PH46A gave a low overall yield, due in large part to the generation of undesired diastereoisomer 5 and the unwanted enantiomer (R,R)-8 during the synthesis. The aim of this work was to carry out a comprehensive investigation into the stereoselective synthesis of PH46A. Significant progress was made on the ketone reduction step, where the use of triisobutylaluminum [TiBA, Al(iBu)3] afforded high selectivity for …