Natural product and natural product-like molecules continue to be important for the development of pharmaceutical agents, as molecules in this class play a vital role in the pipeline for new therapeutics. Among these, tetracyclic terpenoids are privileged, with >100 being FDA-approved drugs. Despite this significant pharmaceutical success, there remain considerable limitations to broad medicinal exploitation of the class due to lingering scientific challenges associated with compound availability. Here, we report a concise asymmetric route to forging natural and unnatural (enantiomeric) C19 and C20 tetracyclic terpenoid skeletons suitable to drive medicinal exploration. While efforts have been focused on establishing the chemical science, early investigations reveal that the emerging chemical technology can deliver compositions of matter that are potent and selective agonists of the estrogen receptor beta, and that are selectively cytotoxic in two different glioblastoma cell lines (U251 and U87).
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Date of publication: 4 June 2019; Nature Communications 10; Article number: 2448
Author information: Wan Shin Kim (1); Zachary A. Shalit (1); Sidney M. Nguyen (2); Emmalie Schoepke (3); Alan Eastman (4); Thomas P. Burris (3); Arti B. Gaur (2); & Glenn C. Micalizio (1)
(1) Dartmouth College, Department of Chemistry, Burke Laboratory, Hanover, NH 03755, USA
(2) Dartmough College, Geisel School of Medicine, Department of Neurology, Lebanon, NH 03756, USA
(3) Center for Clinical Pharmacology, Washington University School of Medicine and St. Louis College of Pharmacy, St. Louis, MO 63110, USA
(4) Dartmouth College, Geisel School of Medicine, Department of Molecular and Systems Biology, Lebanon, NH 03746, USA