Chiroptical sensing of citronellal: systematic development of a stereodynamic probe using the concept of isostericity.

A rationally designed stereodynamic ICD probe carrying two terminal amino functions for chemo- and enantioselective sensing of citronellal is introduced. The sensor shows strong Cotton effects upon diimine formation which can be used for accurate ee determination.

Enantioselective sensing of chiral amino alcohols with a stereodynamic arylacetylene-based probe.

Enantioselective induced circular dichroism analysis of amino alcohols has been accomplished using a conformationally flexible arylacetylene-based probe exhibiting two terminal aldehyde groups. The chirality of the amino alcohol substrates is imprinted on the stereodynamic receptor upon [1 + 2] condensation, which ultimately generates a strong chiroptical response. The distinct induced circular dichroism effects of the diimines obtained can be used for enantioselective sensing and enantiomeric excess determination of a wide range of substrates.

Stereoselective UV sensing of 1,2-diaminocyclohexane isomers based on ligand displacement with a diacridylnaphthalene N,N'-dioxide scandium complex.

Stereoselective displacement of diacridylnaphthalene N,N'-dioxide ligands, 1, from a scandium(III) complex can be used for quantitative detection of 1,2-diaminocyclohexane isomers. The diastereoselective sensing assay with Sc(syn-1)(2) shows excellent linearity between the sample de and the measured UV absorption change, and sensing of mixtures comprising both low and high de values gave results within 5% accuracy. All three stereoisomers of 1,2-diaminocyclohexane can be differentiated using Sc[anti-(-)-1](2) in the same ligand displacement assay.

Enantioselective sensing of amines based on [1 + 1]-, [2 + 2]-, and [1 + 2]-condensation with fluxional arylacetylene-derived dialdehydes.

Four induced circular dichroism (ICD) probes exhibiting a stereodynamic arylacetylene framework and terminal aldehyde units have been prepared. The CD silent sensors generate a strong chiroptical response to substrate-controlled induction of axial chirality upon selective [1 + 1]-, [2 + 2]-, and [1 + 2]-condensation. The intense Cotton effects can be exploited for in situ ICD analysis of the absolute configuration and ee of a wide range of amines.

A stereodynamic probe providing a chiroptical response to substrate-controlled induction of an axially chiral arylacetylene framework.

A stereodynamic probe containing a central 1,4-di(phenylethynyl)benzene rod and two 2-formylphenylethynyl branches has been prepared through a series of Sonogashira cross-coupling reactions with 62% overall yield. This CD silent diarylacetylene-based framework carries two terminal aldehyde groups and provides a strong chiroptical response to substrate-controlled induction of three chiral axes upon diimine formation. The chiral amplification results in intense Cotton effects that can be used for in situ ICD analysis of the absolute configuration and ee of a wide range of amines.

A versatile and practical solvating agent for enantioselective recognition and NMR analysis of protected amines.

The 3,5-dinitrobenzoyl-derived 1-naphthylethyl amide 3 is an attractive CSA for NMR analysis of protected amines. It is readily prepared in a single step and combines practical resolution of diastereomeric complexes due to signal sharpness and effective signal separation. Crystallographic analysis shows that 3 forms a chiral cleft that can selectively bind one enantiomer of a substrate through hydrogen bonding, π-π stacking, and CH/π interactions.

Synthesis and antimalarial activity of new chloroquine analogues carrying a multifunctional linear side chain.

We report the synthesis and in vitro antimalarial activity of several new 4-amino- and 4-alkoxy-7-chloroquinolines carrying a linear dibasic side chain. Many of these chloroquine analogues have submicromolar antimalarial activity versus HB3 (chloroquine sensitive) and Dd2 (chloroquine resistant strain of Plasmodium falciparum) and low resistance indices were obtained in most cases. Importantly, compounds 11-15 and 24 proved to be more potent against Dd2 than chloroquine.

Synthesis and antimalarial activity of new 4-amino-7-chloroquinolyl amides, sulfonamides, ureas and thioureas.

We report the synthesis and in vitro antimalarial activities of more than 50 7-chloro-4-aminoquinolyl-derived sulfonamides 3-8 and 11-26, ureas 19-22, thioureas 23-26, and amides 27-54. Many of the CQ analogues prepared for this study showed submicromolar antimalarial activity versus HB3 (chloroquine sensitive) and Dd2 (chloroquine resistant strains of Plasmodium falciparum) and low resistance indices were obtained in most cases. Systematic variation of the side chain length and introduction of fluorinated aliphatic and aromatic termini revealed promising leads that overcome CQ resistance.

Overcoming drug resistance to heme-targeted antimalarials by systematic side chain variation of 7-chloro-4-aminoquinolines.

Systematic variation of the branching and basicity of the side chain of chloroquine yielded a series of new 7-chloro-4-aminoquinoline derivatives exhibiting high in vitro activity against four different strains of P. falciparum. Many of the compounds tested showed excellent potency against chloroquine sensitive and resistant strains.