Dihydroquinine

Organocatalytic Enantioselective Conjugate Addition of Nitromethane to Benzylidene-2-Benzoyl Acetate: Asymmetric Synthesis of ABT - 627, an Endothelin Receptor Antagonist.[Pubmed:32195223]

Front Chem. 2020 Mar 5;8:135.

First catalytic and enantioselective conjugate addition of nitromethane to benzylidene-2-benzoyl acetate has been developed using Dihydroquinine derived squaramide catalyst with moderate to high selectivities. Asymmetric total synthesis of ABT-627, a potent ETA receptor antagonist is accomplished utilizing the developed method in overall 15.7% yield.

Organocatalyzed asymmetric tandem conjugate addition-protonation of isocyanoacetates to 2-chloroacrylonitrile.[Pubmed:30575842]

Org Biomol Chem. 2019 Jan 16;17(3):639-645.

An efficient organocatalytic asymmetric tandem conjugate addition-protonation of alpha-substituted isocyanoacetates to 2-chloroacrylonitrile catalyzed by Dihydroquinine-derived thiourea has been investigated, affording the corresponding adducts with two non-adjacent tertiary-quaternary stereocenters in excellent yields (up to 99%) along with good to excellent diastereo- and enantioselectivities (up to 20 : 1 dr, up to 95% ee) under mild conditions. The adduct can also be transformed into chiral gamma-lactam by synthetic transformations.

Catalytic Enantio- and Diastereoselective Mannich Addition of TosMIC to Ketimines.[Pubmed:30246415]

Chemistry. 2018 Dec 3;24(67):17660-17664.

Chiral amines bearing a stereocenter in the alpha position are ubiquitous compounds with many applications in the pharmaceutical and agrochemical sectors, as well as in catalysis. Catalytic asymmetric Mannich additions represent a valuable method to access such compounds in enantioenriched form. This work reports the first enantio- and diastereoselective addition of commercially available p-toluenesulfonylmethyl isocyanide (TosMIC) to ketimines, affording 2-imidazolines bearing two contiguous stereocenters, one of which is fully-substituted, with high yields and excellent stereocontrol. The reaction, catalyzed by silver oxide and a Dihydroquinine-derived N,P-ligand, is broad in scope, operationally simple, and scalable. Derivatization of the products provides enantioenriched vicinal diamines, precursors to NHC ligands and sp(3) -rich heterocyclic scaffolds. Computations are used to understand catalysis and rationalize stereoselectivity.

Quantitative determination of major alkaloids in Cinchona bark by Supercritical Fluid Chromatography.[Pubmed:29699870]

J Chromatogr A. 2018 Jun 15;1554:117-122.

Chinoline alkaloids found in Cinchona bark still play an important role in medicine, for example as antimalarial and antiarrhythmic drugs. For the first time Supercritical Fluid Chromatography has been utilized for their separation. Six respective derivatives (dihydroquinidine, Dihydroquinine, quinidine, quinine, cinchonine and cinchonidine) could be resolved in less than 7min, and three of them quantified in crude plant extracts. The optimum stationary phase showed to be an Acquity UPC(2) Torus DEA 1.7mum column, the mobile phase comprised of CO2, acetonitrile, methanol and diethylamine. Method validation confirmed that the procedure is selective, accurate (recovery rates from 97.2% to 103.7%), precise (intra-day /=0.999); at 275nm the observed detection limits were always below 2.5mug/ml. In all of the samples analyzed cinchonine dominated (1.87%-2.30%), followed by quinine and cinchonidine. Their total content ranged from 4.75% to 5.20%. These values are in good agreement with published data, so that due to unmatched speed and environmental friendly character SFC is definitely an excellent alternative for the analysis of these important natural products.