Modular and Highly Stereoselective Approach to All-Carbon Tetrasubstituted Alkenes

A modular and completely stereoselective approach for the construction of all-carbon tetrasubstituted alkenes is described. It is based on the three-fold, sequential metal-catalyzed, cross-coupling functionalization of simple enolphosphate dibromide templates with carbon nucleophiles, affording tetrasubstituted alkenes as single isomers

Regioselective Halogenation of Thiacalix[4]arenes in the <i>Cone</i> and <i>1,3-Alternate</i> Conformations

Monohalogenation of thiacalix[4]­arene in the <i>cone</i> conformation gave either the <i>meta</i>- or <i>para</i>-substituted isomers depending on the halogen and reaction conditions used. Surprisingly, the same reaction with the <i>1,3-alternate</i> conformer led only to the <i>meta</i> isomer. This is the first example of such a conformation-dependent regioselectivity in calixarene/thiacalixarene chemistry. As the halogen-substituted calixarenes are useful synthetic intermediates, this provided the unique opportunity to functionalize the basic skeleton at two different positions

Dimercuration of Calix[4]arenes: Novel Substitution Pattern in Calixarene Chemistry

A mercuration reaction of tetrapropoxycalix[4]­arene immobilized in the <i>cone</i> conformation gave a mixture of two dimercurated products (<i>meta</i>,<i>meta</i> and <i>meta</i>,<i>para</i>) in approximately a 1:1 ratio. Both regioisomers represent inherently chiral compounds, which makes them very attractive for design of novel receptors. As demonstrated by Pd-catalyzed arylation, the different reactivity of HgCl functions in the <i>meta</i>,<i>para</i>-disubstituted isomer opens the door for regioselective introductions of two different functional groups to achieve a substitution pattern so far unknown in calixarene chemistry

Dimercuration of Calix[4]arenes: Novel Substitution Pattern in Calixarene Chemistry

A mercuration reaction of tetrapropoxycalix[4]­arene immobilized in the <i>cone</i> conformation gave a mixture of two dimercurated products (<i>meta</i>,<i>meta</i> and <i>meta</i>,<i>para</i>) in approximately a 1:1 ratio. Both regioisomers represent inherently chiral compounds, which makes them very attractive for design of novel receptors. As demonstrated by Pd-catalyzed arylation, the different reactivity of HgCl functions in the <i>meta</i>,<i>para</i>-disubstituted isomer opens the door for regioselective introductions of two different functional groups to achieve a substitution pattern so far unknown in calixarene chemistry

Dimercuration of Calix[4]arenes: Novel Substitution Pattern in Calixarene Chemistry

A mercuration reaction of tetrapropoxycalix[4]­arene immobilized in the <i>cone</i> conformation gave a mixture of two dimercurated products (<i>meta</i>,<i>meta</i> and <i>meta</i>,<i>para</i>) in approximately a 1:1 ratio. Both regioisomers represent inherently chiral compounds, which makes them very attractive for design of novel receptors. As demonstrated by Pd-catalyzed arylation, the different reactivity of HgCl functions in the <i>meta</i>,<i>para</i>-disubstituted isomer opens the door for regioselective introductions of two different functional groups to achieve a substitution pattern so far unknown in calixarene chemistry

Dimercuration of Calix[4]arenes: Novel Substitution Pattern in Calixarene Chemistry

A mercuration reaction of tetrapropoxycalix[4]­arene immobilized in the <i>cone</i> conformation gave a mixture of two dimercurated products (<i>meta</i>,<i>meta</i> and <i>meta</i>,<i>para</i>) in approximately a 1:1 ratio. Both regioisomers represent inherently chiral compounds, which makes them very attractive for design of novel receptors. As demonstrated by Pd-catalyzed arylation, the different reactivity of HgCl functions in the <i>meta</i>,<i>para</i>-disubstituted isomer opens the door for regioselective introductions of two different functional groups to achieve a substitution pattern so far unknown in calixarene chemistry

Dimercuration of Calix[4]arenes: Novel Substitution Pattern in Calixarene Chemistry

A mercuration reaction of tetrapropoxycalix[4]­arene immobilized in the <i>cone</i> conformation gave a mixture of two dimercurated products (<i>meta</i>,<i>meta</i> and <i>meta</i>,<i>para</i>) in approximately a 1:1 ratio. Both regioisomers represent inherently chiral compounds, which makes them very attractive for design of novel receptors. As demonstrated by Pd-catalyzed arylation, the different reactivity of HgCl functions in the <i>meta</i>,<i>para</i>-disubstituted isomer opens the door for regioselective introductions of two different functional groups to achieve a substitution pattern so far unknown in calixarene chemistry

Synthesis of Thiapillar[6]arenes Bearing Redox-Active (Hydro)quinone Groups. Electrochemical and XRD Study

Pillar[n]arenes are among the newest members of the macrocyclic family. Nevertheless, their conformational behavior and binding properties as well as redox properties of dealkylated pillar[n]arenes are well-studied. At the same time, introducing a heteroatom into a cyclophane macrocycle is already known to alter all the above properties drastically. This study presents a simple synthetic approach based on thia-Michael addition cyclization that readily resulted into hexathiapillar[6]arene with four phenylene units alternated by two redox-active hydroquinone moieties. The straightforward synthesis of the macrocycle enabled a systematic study of its conformation and redox behavior. The modification of hexathiapillar[6]arene afforded five functionalized derivatives, which were studied structurally in detail. The findings revealed interesting redox and structural properties of the macrocycle and its derivatives including the formation of crystal lattices with continuous channels and empty voids

Synthesis of Thiapillar[6]arenes Bearing Redox-Active (Hydro)quinone Groups. Electrochemical and XRD Study

Pillar[n]arenes are among the newest members of the macrocyclic family. Nevertheless, their conformational behavior and binding properties as well as redox properties of dealkylated pillar[n]arenes are well-studied. At the same time, introducing a heteroatom into a cyclophane macrocycle is already known to alter all the above properties drastically. This study presents a simple synthetic approach based on thia-Michael addition cyclization that readily resulted into hexathiapillar[6]arene with four phenylene units alternated by two redox-active hydroquinone moieties. The straightforward synthesis of the macrocycle enabled a systematic study of its conformation and redox behavior. The modification of hexathiapillar[6]arene afforded five functionalized derivatives, which were studied structurally in detail. The findings revealed interesting redox and structural properties of the macrocycle and its derivatives including the formation of crystal lattices with continuous channels and empty voids

Structural Basis for Inhibition of Mycobacterial and Human Adenosine Kinase by 7‑Substituted 7‑(Het)aryl-7-deazaadenine Ribonucleosides

Adenosine kinase (ADK) from <i>Mycobacterium tuberculosis</i> (Mtb) was selected as a target for design of antimycobacterial nucleosides. Screening of 7-(het)­aryl-7-deazaadenine ribonucleosides with Mtb and human (<i>h</i>) ADKs and testing with wild-type and drug-resistant Mtb strains identified specific inhibitors of Mtb ADK with micromolar antimycobacterial activity and low cytotoxicity. X-ray structures of complexes of Mtb and <i>h</i>ADKs with 7-ethynyl-7-deazaadenosine showed differences in inhibitor interactions in the adenosine binding sites. 1D ¹H STD NMR experiments revealed that these inhibitors are readily accommodated into the ATP and adenosine binding sites of Mtb ADK, whereas they bind preferentially into the adenosine site of <i>h</i>ADK. Occupation of the Mtb ADK ATP site with inhibitors and formation of catalytically less competent semiopen conformation of MtbADK after inhibitor binding in the adenosine site explain the lack of phosphorylation of 7-substituted-7-deazaadenosines. Semiempirical quantum mechanical analysis confirmed different affinity of nucleosides for the Mtb ADK adenosine and ATP sites