A flow reactor setup for photochemistry of biphasic gas/liquid reactions.

A home-built microreactor system for light-mediated biphasic gas/liquid reactions was assembled from simple commercial components. This paper describes in full detail the nature and function of the required building elements, the assembly of parts, and the tuning and interdependencies of the most important reactor and reaction parameters. Unlike many commercial thin-film and microchannel reactors, the described set-up operates residence times of up to 30 min which cover the typical rates of many organic reactions. The tubular microreactor was successfully applied to the photooxygenation of hydrocarbons (Schenck ene reaction). Major emphasis was laid on the realization of a constant and highly reproducible gas/liquid slug flow and the effective illumination by an appropriate light source. The optimized set of conditions enabled the shortening of reaction times by more than 99% with equal chemoselectivities. The modular home-made flow reactor can serve as a prototype model for the continuous operation of various other reactions at light/liquid/gas interfaces in student, research, and industrial laboratories.

Modular synthesis of cyclic cis- and trans-1,2-diamine derivatives.

Structurally diverse carbocycles with two vicinal nitrogen-substituents were prepared in expedient three-component reactions from simple amines, aldehydes, and nitroalkenes. trans,trans-6-Nitrocyclohex-2-enyl amines were obtained in a one-pot domino reaction involving condensation, tautomerisation, conjugate addition, and nitro-Mannich cyclisation. Upon employment of less nucleophilic carboxamides, a concerted Diels-Alder cycloaddition mechanism operated to give the corresponding cis,trans-nitrocyclohexenyl amides. Both types of substituted carbocycles offer ample opportunities for chemical manipulations at the core and periphery. Ring oxidation with MnO2 affords substituted nitroarenes. Reduction with Zn/HCl provides access to various trans- and cis-diaminocyclohexenes, respectively, in a straight-forward manner. With enantiopure secondary amines, a two-step synthesis of chiral nitrocyclohexadienes was developed (82-94% ee).

A vHTS approach for the identification of beta-adrenoceptor ligands.

Using a vHTS based on a pharmacophore alignment on known beta3-adrenoceptor ligands, a set of intriguing beta-adrenoceptor ligands was identified, optimization of which resulted in a selective and potent human beta2-AR antagonist.

Thienopyrimidines as ß3-adrenoceptor agonists: hit-to-lead optimization.

Resulting from a vHTS based on a pharmacophore alignment on known ß3-adrenoceptor ligands, an aryloxypropanolamine scaffold comprising a thienopyrimidine moiety was further optimized as a human ß3-AR agonist, yielding a lead compound with an excellent cellular activity of EC(50)=20 pM, selectivity over hß1- and hß2-adrenoceptors and a promising safety profile.