Small-molecule diversity using a skeletal transformation strategy.
[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.
Kumar
Nilesh
N
Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02138, USA.
Kiuchi
Masatoshi
M
Tallarico
John A
JA
Schreiber
Stuart L
SL
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*
D007202:Indicators and Reagents; D011084:Polycyclic Aromatic Hydrocarbons