Fluorous-enhanced multicomponent reactions for making drug-like library scaffolds.
Multicomponent reactions (MCRs) generate multiple bonds in a single reaction process, which is highly efficient to construct relatively complex molecules. Conducting post-MCR modification reactions further increases the molecular complexity and diversity. MCR has become a powerful approach to make drug-like molecules in lead generation chemistry. In fluorous MCR (F-MCR), one of the starting materials is attached to a fluorous tag and used as the limiting agent. After the MCR, the fluorous component is fished out from the reaction mixture and used for post-MCR modifications. The fluorous tag can be finally removed in traceless fashion by displacement or cyclization reactions. Unique fluorous technology such as fluorous solid-phase extraction (F-SPE) facilitates the separation process. Other techniques such as microwave irradiation and plate-to-plate SPE can also be used to make the F-MCR even more efficient. Syntheses of unique heterocyclic and natural product-like library scaffolds using Ugi/de-Boc/cyclization, MCR/Suzuki coupling, and [3+2] cycloaddition/de-tag/cyclization protocols are described in this paper.
Zhang
Wei
W
Fluorous Technologies, Inc., University of Pittsburgh Applied Research Center, 970 William Pitt Way, Pittsburgh, Pennsylvania 15238, USA. w.zhang@fluorous.com
D002625:Chemistry, Organic / Q000379:methods; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D005456:Fluorescent Dyes; D015335:Molecular Probes; D009930:Organic Chemicals / Q000138:chemical synthesis*; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis
D005456:Fluorescent Dyes; D015335:Molecular Probes; D009930:Organic Chemicals; D004364:Pharmaceutical Preparations