| Autor: |
Srinivasulu V; Sharjah Institute for Medical Research, University of Sharjah, P.O. Box 27272, Sharjah, UAE., Schilf P; Lübeck Institute of Experimental Dermatology, University of Lübeck, Ratzeburger Allee 160 23538, Lübeck, Germany., Ibrahim S; Lübeck Institute of Experimental Dermatology, University of Lübeck, Ratzeburger Allee 160 23538, Lübeck, Germany. Saleh.Ibrahim@uksh.de., Khanfar MA; Department of Chemistry, University of Jordan, 11942, Amman, Jordan., Sieburth SM; Department of Chemistry, Temple University, 201 Beury Hall, Philadelphia, PA, 19122, USA., Omar H; Sharjah Institute for Medical Research, University of Sharjah, P.O. Box 27272, Sharjah, UAE.; College of Pharmacy, University of Sharjah, P.O. Box, 27272, Sharjah, UAE.; Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt., Sebastian A; Sharjah Institute for Medical Research, University of Sharjah, P.O. Box 27272, Sharjah, UAE., AlQawasmeh RA; Department of Chemistry, University of Jordan, 11942, Amman, Jordan., O'Connor MJ; New York University, Abu Dhabi, P.O. Box 129188, Saadiyat Island, Abu Dhabi, UAE., Al-Tel TH; Sharjah Institute for Medical Research, University of Sharjah, P.O. Box 27272, Sharjah, UAE. taltal@sharjah.ac.ae.; College of Pharmacy, University of Sharjah, P.O. Box, 27272, Sharjah, UAE. taltal@sharjah.ac.ae. |
| Abstrakt: |
Octahydroindolo[2,3-a]quinolizine ring system forms the basic framework comprised of more than 2000 distinct family members of natural products. Despite the potential applications of this privileged substructure in drug discovery, efficient, atom-economic and modular strategies for its assembly, is underdeveloped. Here we show a one-step build/couple/pair strategy that uniquely allows access to diverse octahydroindolo[2,3-a]quinolizine scaffolds with more than three contiguous chiral centers and broad distribution of molecular shapes via desymmetrization of the oxidative-dearomatization products of phenols. The cascade demonstrates excellent diastereoselectivity, and the enantioselectivity exceeded 99% when amino acids are used as chiral reagents. Furthermore, two diastereoselective reactions for the synthesis of oxocanes and piperazinones, is reported. Phenotypic screening of the octahydroindolo[2,3-a]quinolizine library identifies small molecule probes that selectively suppress mitochondrial membrane potential, ATP contents and elevate the ROS contents in hepatoma cells (Hepa1-6) without altering the immunological activation or reprogramming of T- and B-cells, a promising approach to cancer therapy. |
