Joanna M. Redmond

Synthesis of functionalised 4H-quinolizin-4-ones via tandem Horner-Wadsworth-Emmons olefination/ cyclisation†

4H-Quinolizin-4-ones are a unique class of heterocycle with valuable physicochemical properties and which are emerging as key pharmacophores for a range of biological targets. A tandem Horner-Wadsworth-Emmons olefination/cyclisation method has been developed to allow facile access to substituted 4H-quinolizin-4-ones encoded with a range of functional groups.

Speciation Control During Suzuki–Miyaura Cross‐Coupling of Haloaryl and Haloalkenyl MIDA Boronic Esters

Boronic acid solution speciation can be controlled during the Suzuki-Miyaura cross-coupling of haloaryl N-methyliminodiacetic acid (MIDA) boronic esters to enable the formal homologation of boronic acid derivatives. The reaction is contingent upon control of the basic biphase and is thermodynamically driven: temperature control provides highly chemoselective access to either BMIDA adducts at room temperature or boronic acid pinacol ester (BPin) products at elevated temperature. Control experiments and solubility analyses have provided some insight into the mechanistic operation of the formal homologation process.

Tetrahydroisoquinolines affect the whole-cell phenotype of Mycobacterium tuberculosis by inhibiting the ATP-dependent MurE ligase

Objectives (S)-Leucoxine, isolated from the Colombian Lauraceae tree Rhodostemonodaphne crenaticupula Madriñan, was found to inhibit the growth of Mycobacterium tuberculosis H37Rv. A biomimetic approach for the chemical synthesis of a wide array of 1-substituted tetrahydroisoquinolines was undertaken with the aim of elucidating a common pharmacophore for these compounds with novel mode(s) of anti-TB action. Methods Biomimetic Pictet–Spengler or Bischler–Napieralski synthetic routes were employed followed by an evaluation of the biological activity of the synthesized compounds. Results In this work, the synthesized tetrahydroisoquinolines were found to inhibit the growth of M. tuberculosis H37Rv and affect its whole-cell phenotype as well as the activity of the ATP-dependent MurE ligase, a key enzyme involved in the early stage of cell wall peptidoglycan biosynthesis. Conclusions As the correlation between the MIC and the half-inhibitory enzymatic concentration was not particularly strong, there is a credible possibility that these compounds have pleiotropic mechanism(s) of action in M. tuberculosis.

Modular Construction of Fluoroarenes from a New Difluorinated Building Block by Cross-Coupling/Electrocyclisation/Dehydrofluorination Reactions

Palladium-catalysed coupling reactions based on a novel and easy-to-synthesise difluorinated organotrifluoroborate were used to assemble precursors to 6π-electrocyclisations of three different types. Electrocyclisations took place at temperatures between 90 and 240 °C, depending on the central component of the π-system; nonaromatic trienes were most reactive, but even systems that required the temporary dearomatisation of two arenyl subunits underwent electrocyclisation, albeit at elevated temperatures. Photochemical conditions were effective for these more demanding reactions. The package of methods delivered a structurally diverse set of fluorinated arenes, spanning a 20 kcal mol(-1) range of reactivity, by a flexible route.