You are here

ACS Comb Sci DOI:10.1021/co300098v

Application of a catalytic asymmetric Povarov reaction using chiral ureas to the synthesis of a tetrahydroquinoline library.

Publication TypeJournal Article
Year of Publication2012
AuthorsGerard, B, O'Shea, MWelzel, Donckele, E, Kesavan, S, Akella, LB, Xu, H, Jacobsen, EN, Marcaurelle, LA
JournalACS Comb Sci
Volume14
Issue11
Pages621-30
Date Published2012 Nov 12
ISSN2156-8944
KeywordsCatalysis, Feasibility Studies, Quinolones, Stereoisomerism, Structure-Activity Relationship, Urea
Abstract

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.

DOI10.1021/co300098v
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/23088641?dopt=Abstract

Alternate JournalACS Comb Sci
PubMed ID23088641
PubMed Central IDPMC3577964
Grant ListU54 RL1CA133834 / CA / NCI NIH HHS / United States
UL1DE019585 / DE / NIDCR NIH HHS / United States
RL1HG004671 / HG / NHGRI NIH HHS / United States
UL1 DE019585 / DE / NIDCR NIH HHS / United States
RL1GM084437 / GM / NIGMS NIH HHS / United States
P50 GM069721 / GM / NIGMS NIH HHS / United States
RL1 GM084437 / GM / NIGMS NIH HHS / United States
RL1 HG004671 / HG / NHGRI NIH HHS / United States
RL1 CA133834 / CA / NCI NIH HHS / United States