Conformational photoswitching of a synthetic peptide foldamer bound within a phospholipid bilayer

The dynamic properties of foldamers, synthetic molecules that mimic folded biomolecules, have mainly been explored in free solution.We report on the design, synthesis, and conformational behavior of photoresponsive foldamers bound in a phospholipid bilayer akin to a biological membrane phase. These molecules contain a chromophore, which can be switched between two configurations by different wavelengths of light, attached to a helical synthetic peptide that both promotes membrane insertion and communicates conformational change along its length. Light-induced structural changes in the chromophore are translated into global conformational changes, which are detected by monitoring the solid-state 19 F nuclear magnetic resonance signals of a remote fluorine-containing residue located 1 to 2 nanometers away. The behavior of the foldamers in the membrane phase is similar to that of analogous compounds in organic solvents

Stereospecific Intramolecular Arylation of 2- and 3-Pyridyl Substituted Alkylamines via Configurationally Stable α-Pyridyl Organolithiums

Treatment of <i>N</i>′-aryl urea derivatives of enantiomerically enriched α-(2-pyridyl) and α-(3-pyridyl)­alkylamines with a base leads to the migration of the <i>N</i>′-aryl substituent from N to C in a ‘nonclassical’ intramolecular nucleophilic aromatic substitution reaction. Both electron-rich and -poor rings migrate successfully. A new quaternary stereogenic center is formed adjacent to the pyridine ring with high stereospecificity, even when the intermediate anion is a presumably planar 2-picolyllithium. Base hydrolysis of the urea gives enantiomerically enriched α-pyridylalkylamines

Evolving New Chemistry: Biocatalysis for the Synthesis of Amine-Containing Pharmaceuticals

Biocatalysis has become an attractive tool in modern synthetic chemistry both in academic and industrial settings, offering access to enantiopure molecules. In industry, biocatalysis found use in small molecule pharmaceutical development. For several amine-containing drugs, biotransformations were applied in the process routes, improving the original syntheses employing classical chemical methods. This review illustrates how and why biocatalysis has been applied to create safer, more efficient and less costly processes for the manufacture of chiral amine-containing pharmaceuticals and alkaloids. Several enzyme classes have been applied to syntheses of natural products, pharmaceutical products and their intermediates, including transaminases, imine reductases, monoamine oxidases and Pictet-Spenglerases. The routes with and without application of biocatalysis are compared, and the potential of these enzyme classes in redesigned synthetic routes to natural products, alkaloids and high-value chemicals is evaluated, using syntheses of sitagliptin, suvorexant, PF-04449913, MK-7246, vernakalant, GSK-2879552, boceprevir and (−)-strictosidine as examples. Application of biocatalysis in the synthesis of amine-containing pharmaceuticals constitutes a greener alternative to transition metal-catalysed routes, facilitates installation of chiral amine functionalities at a late stage of the synthesis and provides exquisite stereocontrol. Opportunities and challenges of biocatalysis for the synthesis of chiral amines are reviewed with respect to use in drug discovery and development

Visible-Light-Mediated Generation of Nitrile Oxides for the Photoredox Synthesis of Isoxazolines and Isoxazoles

Visible-light photoredox catalysis enables the synthesis of biologically relevant isoxazolines and isoxazoles from hydroxyimino acids.</p

CCDC 1415763: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 927332: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

Chemoenzymatic Synthesis of Substituted Azepanes by Sequential Biocatalytic Reduction and Organolithium-Mediated Rearrangement

Enantioenriched 2-aryl azepanes and 2-arylbenzazepines were generated biocatalytically by asymmetric reductive amination using imine reductases or by deracemization using monoamine oxidases. The amines were converted to the corresponding <i>N</i>′-aryl ureas, which rearranged on treatment with base with stereospecific transfer of the aryl substituent to the 2-position of the heterocycle via a configurationally stable benzyllithium intermediate. The products are previously inaccessible enantioenriched 2,2-disubstituted azepanes and benzazepines

CCDC 913266: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures