Application of a Catalytic Asymmetric Povarov Reaction using Chiral Ureas to the Synthesis of a Tetrahydroquinoline Library

作者：Gerard Baudouin; O'Shea Morgan Welzel; Donckele Etienne; Kesavan Sarathy; Akella Lakshmi B; Xu Hao; Jacobsen Eric N; Marcaurelle Lisa A^*

来源：ACS Combinatorial Science, 2012, 14(11): 621-630.

DOI：10.1021/co300098v

• Povarov reaction
• chiral urea
• tetrahydroquinoline
• asymmetric
• solid-phase

A 2328-membered library of 2,3,4-trisubstituted tetrahydroquinolines was produced using a combination of solution- and solid-phase synthesis techniques. A tetrahydroquinoline (THQ) scaffold was prepared via an asymmetric Povarov reaction using cooperative catalysis to generate three contiguous stereogenic centers. A matrix of 4 stereoisomers of the THQ scaffold was prepared to enable the development of stereo/structure-activity relationships (SSAR) upon biological testing. A sparse matrix design strategy was employed to select library members to be synthesized with the goal of generating a diverse collection of tetrahydroquinolines with physicochemical properties suitable for downstream discovery.

• 出版日期2012-11