Document Type
Article
Rights
Available under a Creative Commons Attribution Non-Commercial Share Alike 4.0 International Licence
Disciplines
1.4 CHEMICAL SCIENCES, 1.6 BIOLOGICAL SCIENCES
Abstract
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 the target diastereoisomer (rac)-6, compared to the unfavorable ratio obtained using a previous process. This enabled a multikilo scale synthesis of PH46A in a GMP environment. Further, a brief proof-of-principle investigation was carried out using an achiral phase transfer catalyst (PTC) for alkylation at the methine carbon of the parent indanone.
DOI
https://doi.org/10.1021/acs.oprd.7b00258
Recommended Citation
Cumming, G., Zhang, T., Scalabrino, G., Frankish, N. and Sheridan, H. (2017). Investigation of the Stereoselective Synthesis of the Indane Dimer PH46A, a New Potential Anti-inflammatory Agent. Journal of Organic Process Research & Development 21, pp.1972-1979. doi:10.1021/acs.oprd.7b00258
Funder
The Wellcome Trust UK, Enterprise Ireland
Publication Details
Journal of Organic Research & Development