Piotr Łyżwa

Asymmetric addition of dialkyl phosphite and diamido phosphite anions to chiral, enantiopure sulfinimines: a new, convenient route to enantiomeric α-aminophosphonic acids

Abstract Lithium or sodium dialkyl phosphites and diamido phosphites 3 undergo addition to (+)-(S)-benzylidene-p-toluenesulfinamide 2 affording N-sulfinyl-α-aminophosphonates 4 in a diastereoisomeric ratio from 63:37 to 94:6. The major diastereoisomers formed in addition of lithium dimethyl phosphite 3a and lithium bis-diethylamido phosphite 3e to (+)-(S)- 2 were separated and converted into enantiopure (+)-(R)- and (−)-(S)-α-aminobenzyl phosphonic acids 5 , respectively.

New procedures for the resolution of chiral tert-butylphenylphosphine oxide and some of its reactions

Abstract Racemic t -butylphenylphosphine oxide was resolved via formation of diastereoisomeric complexes with (+)-( R )-1,1′-binaphthalene-2,2′-diol and (+)-( S )-mandelic acid. With the latter complexing agent, separation of the essentially enantiopure (−)-( S )-enantiomer was achieved in a single complexation process. Addition of paraformaldehyde to this enantiomer gave α-hydroxymethyl- t -butylphenylphosphine oxide with high stereoselectivity and retention of configuration at phosphorus while its reaction with methyl bromoacetate in methanol/sodium methoxide resulted in the formation of methyl t -butylphenylphosphinate with inversion at phosphorus.

Absolute configurations, predominant conformations, and tautomeric structures of enantiomeric tert-butylphenylphosphinothioic acid

Vibrational absorption and circular dichroism spectra of dextrorotatory, levorotatory, and racemic mixture of tert-butylphenylphosphinothioic acid have been measured in CCl(4) solutions in the 2000-900 cm(-1) region. The conformations for both tautomeric structures of (S)-tert-butylphenylphosphinothioic acid are investigated using the B3LYP functional with the 6-31G* basis set. For the most stable conformation, the absorption and VCD spectra are predicted ab initio using the B3LYP functional with 6-31G*, 6-311G(2d, 2p), 6-31+G, and 6-311G(3df, 3pd) basis sets. A different functional, B3PW91, was also used with the 6-31G* basis set. The predicted spectra are compared to the experimental spectra. The comparison indicates that (-)-tert-butylphenylphosphinothioic acid is of the (S)-configuration and exists in only one tautomeric structure and one conformation in CCl(4) solution.

A highly efficient asymmetric synthesis of β-aminophosphonic acids, via addition of α-phosphonate carbanions to chiral, enantiopure sulfinimines

Addition of α-phosphonate carbanions to (S)-sulfinimines 1 affords N-sulfinyl β-aminophosphonates 2 in a diastereoisomeric ratio from 5:1 to 10:1; the major diastereoisomers of 2, after separation, are converted to the corresponding β-aminophosphonates 3 or to (+)-β-amino-β-phenylethane phosphonic acid 4, whose absolute configuration was established as (R) by X-ray crystallography.

A new efficient procedure for asymmetric synthesis of α-aminophosphonic acids via addition of lithiated bis(diethylamino)phosphine borane complex to enantiopure sulfinimines

Abstract The addition of lithiated bis(diethylamino)phosphine borane complex to enantiopure p-toluenesulfinimines is highly diastereoselective, affording the corresponding addition products with high efficiency (yields from 72 to 100%). The addition products were readily converted into α-amino-α-arylmethylphosphonic acids with high enantiomeric purities (from 72 to >98%).

The Comparison of MTT and CVS Assays for the Assessment of Anticancer Agent Interactions.

Multiple in vitro tests are widely applied to assess the anticancer activity of new compounds, including their combinations and interactions with other drugs. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay is one of the most commonly used assays to assess the efficacy and interactions of anticancer agents. However, it can be significantly influenced by compounds that modify cell metabolism and reaction conditions. Therefore, several assays are sometimes used to screen for potential anticancer drugs. However, the majority of drug interactions are evaluated only with this single method. The aim of our studies was to verify whether the choice of an assay has an impact on determining the type of interaction and to identify the source of discrepancies. We compared the accuracy of MTT and CVS (crystal violet staining) assays in the interaction of two compounds characterized by similar anticancer activity: isothiocyanates (ITCs) and Selol. Confocal microscopy studies were carried out to assess the influence of these compounds on the reactive oxygen species (ROS) level, mitochondrial membrane potential, dead-to-live cell ratio and MTT-tetrazolium salt reduction rate. The MTT assay was less reliable than CVS. The MTT test of Selol and 2-oxoheptyl ITC, which affected the ROS level and MTT reduction rate, gave false negative (2-oxoheptyl ITC) or false positive (Selol) results. As a consequence, the MTT assay identified an antagonistic interaction between Selol and ITC, while the metabolism-independent CVS test identified an additive or synergistic interaction. In this paper, we show for the first time that the test assay may change the interpretation of the compound interaction. Therefore, the test method should be chosen with caution, considering the mechanism of action of the compound.

Asymmetric synthesis of aminophosphonic acids mediated by chiral sulfinyl auxiliary: Recent advances

New approaches to asymmetric synthesis of α-, β- and γ-aminophosphonic acids using enantiopure p-toluenesulfinimines as key reagents are reported. The utility of the devised methods is illustrated by the syntheses of enantiomeric aminophosphonic acids such as AP4, AP3, and its 3-amino isomer.

The first efficient bovine serum albumin catalyzed asymmetric oxidation of tertiary amines to the corresponding N-oxides via kinetic dynamic resolution

Unsymmetrical teriary amines were oxidized with a few oxidants in the presence of bovine serum albumin to give the corresponding N-oxides of the highest optical purity ever reported (up to 66%) for the reaction of asymmetric oxidation of amines via their kinetic dynamic resolution.

Chiral Sulfinimines in Asymmetric Synthesis of Enantiomeric Aminophosphonic Acids

Abstract Aminophosphonic acids have become important in different fields of chemistry, medicine and agriculture. In this review article, we highlight a new strategy developed in the authors laboratory of asymmetric synthesis of enantiomeric aminophosphonic acid that users chiral sulfinimines as reagents. A key reaction in the synthesis of enantiopure α-, β- and γ-aminophosphonic acids is a highly or fully diastereoselective addition of trivalent phosphorus nucleophiles and α-phosphonate carbanions to enantiopure sulfinimines. The steric course of these addition reactions is rationalized. The usefulness of the sulfinimine methodology is demonstrated by the synthesis of biologically active enantiopure 2-amino-3-phosphonopropanoic acid (AP3), 2-amino-4-phosphonobutanoic acid (AP4) and phosphoemeriamine. GRAPHICAL ABSTRACT

Stereoselective Reactions at the α-Carbon Atom in Organosulfur Compounds

Abstract The present state of knowledge concerning the formation of chiral carbon centers α to various sulfur substituents is reviewed. All the data are classified according to the valency of the sulfur in the sulfur-containing moiety. Thus, there are sections devoted to the formation of chiral carbon α to sulfenyl, sulfinyl and sulfonyl groups and to other, less common sulfur substituents. Within the sections appropriate subsections, concerning particular reactions, are included which allow the reader to find easily the proper subject.