| Autor: |
Wright BA; Department of Chemistry, University of California, Berkeley, California 94720, United States., Matviitsuk A; Janssen Research and Development, San Diego, California 92121, United States., Black MJ; Department of Chemistry, University of California, Berkeley, California 94720, United States., García-Reynaga P; Janssen Research and Development, San Diego, California 92121, United States., Hanna LE; Janssen Research and Development, San Diego, California 92121, United States., Herrmann AT; Janssen Research and Development, San Diego, California 92121, United States., Ameriks MK; Janssen Research and Development, San Diego, California 92121, United States., Sarpong R; Department of Chemistry, University of California, Berkeley, California 94720, United States., Lebold TP; Janssen Research and Development, San Diego, California 92121, United States. |
| Abstrakt: |
Azabicyclo[2.1.1]hexanes (aza-BCHs) and bicyclo[1.1.1]pentanes (BCPs) have emerged as attractive classes of sp 3 -rich cores for replacing flat, aromatic groups with metabolically resistant, three-dimensional frameworks in drug scaffolds. Strategies to directly convert, or "scaffold hop", between these bioisosteric subclasses through single-atom skeletal editing would enable efficient interpolation within this valuable chemical space. Herein, we describe a strategy to "scaffold hop" between aza-BCH and BCP cores through a nitrogen-deleting skeletal edit. Photochemical [2+2] cycloadditions, used to prepare multifunctionalized aza-BCH frameworks, are coupled with a subsequent deamination step to afford bridge-functionalized BCPs, for which few synthetic solutions currently exist. The modular sequence provides access to various privileged bridged bicycles of pharmaceutical relevance. |
