Tiina Saloranta

Heterogeneous Chemoenzymatic Catalyst Combinations for One‐Pot Dynamic Kinetic Resolution Applications

Heterogeneously catalyzed one‐pot reactions combining individual reaction steps into sequences enhance the efficiencies of overall chemical processes by reducing costs, time, and labor efforts. This minireview focuses on the production of chiral compounds by using dynamic kinetic resolution (DKR) and related sequential reactions, utilizing heterogeneous and immobilized metal catalysts and enzymes. Enzymes, especially lipases, often possess high chemical, stereo‐, and regiospecificities under mild reaction conditions. Supported transition‐metal catalysts are effective and widely used for various chemical transformations including racemization and hydrogenation reactions. This minireview discusses both the early and important applications, as well as modern state‐of‐the‐art processes, in which different catalyst combinations are utilized. Also catalyst compatibility issues, including catalyst inhibition and applicability are addressed with specific focus on the racemization catalysts applied in DKRs. Finally, some examples on the utilization of heterogeneous catalysts in flow reactors are presented.

Converting Unprotected Monosaccharides into Functionalised Lactols in Aqueous Media: Metal‐Mediated Allylation Combined with Tandem Hydroformylation–Cyclisation

From biomass to fine chemicals: A highly regioselective reaction sequence (see scheme) combining a metal-mediated allylation and tandem hydroformylation-cyclisation for converting unprotected monosaccharides into multifuntionalised lactol structures is presented. The reaction sequence is performed in aqueous media without the need for any protective groups.

Dynamic Kinetic Resolution of rac-2-Hydroxy-1-indanone by using a Heterogeneous Ru(OH)3/Al2O3 Racemization Catalyst and Lipase

Kinetic resolution and dynamic kinetic resolution, in particular, provide practical tools for synthesis of enantiomerically pure compounds. In the present work, the resolution of rac‐2‐hydroxy‐1‐indanone and racemization of (S)‐2‐hydroxy‐1‐indanone were investigated. Immobilized lipase AK (Pseudomonas fluorescens) was found as the best enzyme catalyst for kinetic resolution and ruthenium supported on Al2O3 as a potential heterogeneous catalyst for racemization of the starting material. By combining the two reactions, a simple dynamic kinetic resolution of rac‐2‐hydroxy‐1‐indanone producing (R)‐1‐oxo‐indan‐2‐yl butanoate was developed. Under optimal conditions, the product was obtained in 92 % ee at approximately 90 % conversion.

Evaluation of Immunostimulatory Activities of Synthetic Mannose-Containing Structures Mimicking the β-(1→2)-Linked Cell Wall Mannans of Candida albicans

ABSTRACT Immunostimulatory properties of synthetic structures mimicking the β-(1→2)-linked mannans of Candida albicans were evaluated in vitro. Contrary to earlier observations, tumor necrosis factor (TNF) production was not detected after stimulation with mannotetraose in mouse macrophages. Divalent disaccharide 1,4-bis(α-d-mannopyranosyloxy)butane induced TNF and some molecules induced low levels of gamma interferon (IFN-γ) in human peripheral blood mononuclear cells (PBMC).

Increasing the amphiphilicity of an estradiol based steroid structure by Barbier-allylation – ring-closing metathesis – dihydroxylation sequence

Polyhydroxylated steroids, such as brassinosteroids, phytoecdysteroids and steroid saponins, are structurally attractive compounds possessing a number of interesting biological properties. Accordingly, development of synthetic procedures to build steroid based structures mimicking the naturally occurring hydrophilic steroids is of topical interest. In the present work, a D-secoestrone derivative was modified further by Barbier-allylation - ring-closing metathesis - dihydroxylation sequence with the aim to prepare steroid based structures with limited hydrophilicity. A straightforward synthesis route was developed with the isolated yield for each step ranging from good to excellent. All compounds prepared were fully characterized by NMR spectroscopic techniques and completely assigned (1)H and (13)C spectra are reported herein. Finally, the effects of the synthesized amphiphilic steroid derivatives on the proliferation of cancer cells are reported and discussed.

Synthesis of novel zwitterionic cellulose beads by oxidation and coupling chemistry in water

The design and synthesis of polysaccharide-based materials utilizing a systematic approach is essential to develop sustainable and biodegradable value added products. In this work, new zwitterionic cellulose beads of desired size range were prepared via spin drop atomization followed by sol gel transition technique. Carboxylic acid (COOH) and carbonyl (C=O) moieties were generated using NaClO2/NaClO/TEMPO mediated oxidation system under heterogenous reaction conditions. Coupling reaction between carboxymethyl trimethylammonium chloride hydrazide (Girard’s reagent T) and carbonyl functionalities on cellulose resulted in the formation of stable hydrazone groups. A variation in molar ratio of NaClO2, NaClO and TEMPO were studied to understand the effect of each reagent on the generation of oxidized products. COOH and C=O content was determined by conductometric titrations and oximation with hydroxylamine hydrochloride followed by elemental analysis, respectively. Evidence of functionalization was obtained with ATR-FTIR, Raman, solid state 13C NMR spectroscopic studies and ToF–SIMS analysis. Morphological changes were studied by FE-SEM. The increased porosity and hydrophilicity of zwitterionic beads provides a platform for the future application of these beads in separation of biomolecules, chiral molecules, immobilization of proteins and enzymes and encapsulation of zwitterionic drugs.

Cytotoxic activity of some glycoconjugates including saponins and anthracyclines

Many different glycoconjugates, including saponins (e.g., hellebrin) and anthracyclines (e.g., doxorubicin), are known to display cytotoxic activities. In recent work, we have developed synthetic protocols for the synthesis of various glycoconjugates, focusing on glycosylation methods for different classes of biomolecules. Simultaneously a number of saponins and anthracyclines have been generated. In this note, the cytotoxic activities of these synthesized compounds are briefly addressed.

Bridging Organic Chemistry and Heterogeneous Catalysis

This special issue of Topics in Catalysis was aimed to collect a number of contributions that approach the topics of organic chemistry and heterogeneous catalysis from different angles, thereby building the foundations for future bridges between these two fields. While organic chemistry often uses heterogeneous catalysis as a tool in some reactions, such as hydrogenation, there are a number of specific issues in heterogeneous catalysis related to preparation of inorganic and transition metal catalysts, their characterization, catalytic kinetics and mass transfer, which clearly go beyond the competence of classically trained organic chemists. Likewise, molecular aspects of organic reactions, special terminology and characterization tools of organic chemistry often distract specialists in heterogeneous catalysis and catalytic reaction engineering. Moreover, development of appropriated catalysts for a particular reaction in the field of fine chemicals is, in fact, very time consuming and is not often economically justified. Organic chemists are often using ‘‘on-shelf’’ heterogeneous catalysts, not suitable for a particular process from the viewpoint of active metal nature, loading, dispersion, support properties, pore structure, etc. However, the rapid development of nanoscience and its penetration even in organic chemistry is leading to frequent attempts to synthesize 100 % selective heterogeneous catalysts working with molecular precision. There are already several examples of successful marriages between heterogeneous catalysis and organic chemistry achieved through intense collaboration between specialists in these two domains. Alternatively, somewhat different skills and knowledge of these disciplines can be developed in one person. Such fine example of incorporation of these skills in one personality was our dear friend, colleague and former student Dr. Igor Busygin (1980–2015), to whose memory this special issue is dedicated.

Chapter 6:Oligosaccharides for Pharmaceutical Applications

Carbohydrates, being the most abundant class of biopolymers on earth, have, due to their structural diversity and inherent chirality, been subject to comprehensive biological investigations. Their biological importance is unquestionable, as a wide range of biological recognition and communication phenomena depend on complex oligo- and polysaccharide structures. This also makes carbohydrates attractive targets for developing new pharmaceuticals. In this chapter, a fundamental overview of the synthesis of oligosaccharides from the viewpoint of both traditional synthetic methods as well as fully automated methodologies is provided. Furthermore, selected commercially available oligosaccharide pharmaceuticals as well as promising new compounds under development are briefly discussed.