ABSTRACT
We report a new thiourea-Brønsted acid cooperative catalytic system for the enantioselective cyanosilylation of aldehydes with yields up to 90% and enantioselectivities up to 88%. The addition of an achiral acid was found to be crucial for high asymmetric induction. Mechanistic investigations using a combination of NMR, ESI-MS, and density functional theory computations (including solvent corrections) at the M06/6-31G(d,p) level of theory suggest that the key catalytic species results from the cooperative interaction of bifunctional thioureas and an achiral acid that form well-defined chiral hydrogen-bonding environments.
Subject(s)
Acids/chemistry , Aldehydes/chemistry , Cyanides/chemistry , Nitriles/chemical synthesis , Thiourea/chemistry , Trimethylsilyl Compounds/chemistry , Catalysis , Molecular Structure , Nitriles/chemistry , StereoisomerismABSTRACT
In this study, we used the single cell gel electrophoresis (SCGE) assay and the micronucleus (MN) test to investigate the DNA damaging effects and the antigenotoxic potencies of three structurally related ITCs in human HepG2 cells. The results show that all three ITCs possess the characteristic of a "Janus" compound, i.e., they exert both significant genotoxicity and antigenotoxicity, depending on the concentrations used in the test systems applied. Regression line analysis of the results derived by SCGE analysis showed genotoxic potency of the ITCs in the following order: 3-methylthiopropyl ITC (MTPITC) > 4-methylthiobutyl ITC (MTBITC) > 5-methylthiopentyl ITC (MTPeITC); however, this order in genotoxic potency was not confirmed by MN analysis. Additionally, the MN test showed significant mutagenicity of the test substances at higher concentrations when compared with the SCGE assay. Twenty-four hour-treatment of the cells with the ITCs, followed by a 1-hr recovery period, showed significant DNA repair in the SCGE assay at a concentration > or =10 microM MTPITC, > or =3 microM MTBITC, and > or =0.1 microM MTPeITC, respectively. In antigenotoxicity studies, the most effective concentration of MTPITC and MTPeITC toward B(a)P-induced DNA damage was 0.1 muM in both test systems. MTBITC suppressed MN formation in B(a)P-treated cells to the background level at a concentration of 1 muM. The ambivalent character of the ITCs under studymust be further clarified, especially in the possiblecontext of high dose therapeutic applications.
Subject(s)
Anticarcinogenic Agents/pharmacology , DNA Damage , DNA Repair , Isothiocyanates/pharmacology , Micronuclei, Chromosome-Defective/chemically induced , Mutagens/pharmacology , Anticarcinogenic Agents/chemistry , Anticarcinogenic Agents/isolation & purification , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Comet Assay , Dose-Response Relationship, Drug , Humans , Isothiocyanates/chemistry , Isothiocyanates/isolation & purification , Micronucleus Tests , Molecular Structure , Mutagens/chemistry , Mutagens/isolation & purification , Plants, Edible/chemistry , Regression Analysis , Structure-Activity RelationshipABSTRACT
We present a mild and efficient method for the completely regioselective alcoholysis of styrene oxides utilizing a cooperative Brønsted acid-type organocatalytic system comprised of mandelic acid (1 mol %) and N,N'-bis-[3,5-bis-(trifluoromethyl)phenyl]-thiourea (1 mol %). Various styrene oxides are readily transformed into their corresponding beta-alkoxy alcohols in good to excellent yields at full conversion. Simple aliphatic and sterically demanding, as well as unsaturated and acid-sensitive alcohols can be employed.
