Daniel Paprocki

Efficient Passerini reactions in an aqueous vesicle system

As an example of a one-pot multicomponent reaction, the formation of α-acyloxy carboxamides from a carboxylic acid, an aldehyde and an isocyanide (Passerini reaction) was investigated in aqueous solution in the presence of different types of surfactants. With dioctadecyldimethylammonium bromide (DODAB), a known vesicle-forming cationic surfactant, the reaction with hydrophobic starting materials proceeded with higher yields than without DODAB and with higher yields than in dichloromethane. These results demonstrate the potential of aqueous surfactant vesicle systems as promoters of multicomponent reactions.

Environmentally friendly approach to α-acyloxy carboxamides: Via a chemoenzymatic cascade

A new, green route for the synthesis of α-acyloxy carboxamides from an alcohol, a carboxylic acid and an isocyanide was developed. The reaction comprises the aerobic oxidation of an alcohol to the corresponding aldehyde, catalyzed by the Trametes versicolor laccase/TEMPO system, followed by a one pot Passerini reaction in an aqueous surfactant medium. The influence of different types of surfactants on the reaction efficiency was investigated. The best results were obtained by employing dioctadecyldimethylammonium bromide (DODAB), a known vesicle-forming cationic surfactant. Importantly, apart from the metalloenzyme used, the described procedure toward α-acyloxy carboxamides is metal-free and does not require hazardous organic solvents, what makes it environmentally friendly.

Enzymatic Ugi Reaction with Amines and Cyclic Imines

The application of the Ugi reaction to the construction of new peptide scaffolds is an important goal of organic chemistry. To date, there are no examples of the Ugi reaction being performed with a cyclic imine and amine simultaneously. The application of 2-substituted cyclic imines in an enzymatic three-component Ugi-type reaction provides an elegant and attractive synthesis of substituted pyrrolidine and piperidine derivatives in up to 60 % yield. Results on studies of the selection of an enzyme, amount of water, and solvent used in a novel three-component Ugi reaction and the limitations thereof are reported herein. The presented methodology exploiting enzyme promiscuity in the multicomponent reaction fulfills the requirements associated with green chemistry. Several methods, such as isotope labeling and enzyme inhibition, were used to probe the possible mechanism of this complex synthesis. This research is the first example of an enzyme-catalyzed Ugi-type reaction with an imine, amine, and isocyanide.

Efficient Ugi reactions in an aqueous vesicle system

A new, alternative route for the synthesis of a variety of α-aminoacyl amides via the four-component Ugi reaction in the presence of different types of surfactants was investigated. The best results were obtained if the reaction was carried out in the presence of either didodecyldimethylammonium bromide (DDAB) vesicles or Triton X-100 micelles. The presence of vesicles or micelles in these systems was confirmed by applying dynamic light scattering (DLS) and fluorescence measurements. Additionally, detailed studies of the dependence on the concentration of the two surfactants and on their reusability were performed. The obtained results demonstrate the beneficial effect aqueous surfactant systems may have on the course of the Ugi-multicomponent reaction.

Self-immolative versatile fluorogenic probes for screening of hydrolytic enzyme activity

Enzyme triggered probes with a self-immolative linker for rapid and sensitive hydrolase detection through a cascade reaction have been reported. Their utility was proved by the preparation of three model compounds and their evaluation as enzyme substrates and demonstration of their applicability as fluorogenic probes for screening lipase, esterase and protease activities. These probes represent a new class of fluorogenic compounds, are stable under aqueous conditions and not susceptible to nonspecific degradation. The utilization of the carbamate cleavable linkage in a probe structure allows moving away of the bulky fluorophore from the enzyme recognition unit and targets different classes of enzymes with the same substrate.

Enzyme-Promoted Asymmetric Tandem Passerini Reaction

A versatile and highly efficient three‐step, one‐pot, enzyme‐promoted Passerini tandem reaction has been developed. The chemoenzymatic sequence involved simultaneous enzyme catalyzed hydrolysis, subsequent Passerini reaction, and enzymatic kinetic resolution of the Passerini product. This methodology combines the diversity delivered by multicomponent reactions with the selectivity of biocatalysts, which results in efficient synthesis of the target compounds with excellent enantiomeric excesses of up to 99 %. With a small set of substrates, a large library of complex molecules was obtained within a short time by using the developed procedure.

The sustainable synthesis of peptidomimetics via chemoenzymatic tandem oxidation–Ugi reaction

A simply and green synthetic protocol based on the selective laccase-oxidation of alcohol to a corresponding aldehyde and a following Ugi reaction in a micellar system made of SDS was developed and is reported herein. Special emphasis was placed on the metal-free chemoenzymatic tandem reaction based on alcohol oxidation strategies using molecular oxygen from air, followed by an Ugi reaction. The reaction was carried out without the use of a transition metal or organic solvents as a reaction medium. The presented protocol offers an efficient and environmentally friendly procedure.

Multicomponent reactions accelerated by aqueous micelles

Multicomponent reactions are powerful synthetic tools for the efficient creation of complex organic molecules in an one-pot one-step fashion. Moreover, the amount of solvents and energy needed for separation and purification of intermediates is significantly reduced what is beneficial from the green chemistry issues point of view. This review highlights the development of multicomponent reactions conducted using aqueous micelles systems during the last two decades.