title: Small-molecule diversity using a skeletal transformation strategy.
abstract: [reaction: see text] We describe a short synthetic sequence resulting in >4000 skeletally diverse small molecules that have three distinct skeletal frameworks among other unique structural features. The sequence entails skeletal transformations pioneered by Winterfeldt and co-workers. We use epoxide ring openings and subsequent functionalizations that provide, e.g., spirocyclic oxazolidines, Lewis acid catalyzed Diels-Alder reactions of a steroid-derived diene that afford stable and isolable ring B adducts, and subsequent retro-Diels-Alder fragmentations that yield 14-membered paracyclophanes.
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02138, USA.
authors.forename: Nilesh
authors.initials: N
authors.lastname: Kumar
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kiuchi
authors.forename: John A
authors.initials: JA
authors.lastname: Tallarico
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Schreiber
mesh_terms: D002384:Catalysis; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003500:Cyclization; D007202:Indicators and Reagents; D015394:Molecular Structure; D011084:Polycyclic Aromatic Hydrocarbons / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D007202:Indicators and Reagents; D011084:Polycyclic Aromatic Hydrocarbons