Current Organic Chemistry - Volume 17, Issue 11, 2013

Cancer is the principal cause of death in economically developed countries and the second leading cause of death in developing countries, and this disease is very rapidly growing as a result of both population aging and adoption of cancer-associated routine choices including smoking, physical sedentariness, and ‘‘westernized’’ nourishments. Thus, there is an increasing demand on anticancer drugs, and this demand must be focussed under Green Chemistry postulates, in order to increase the sustainability of Pharmaceutical Industry. In this sense, the use of biocatalyzed protocols in the preparation of those drugs is reporting considerable advantages, especially when water is used as solvent, because of its green behaviour. In this paper, different examples will be shown illustrating this topic.

According to the Green Chemistry principles, water is the first choice solvent to reduce chemical waste and environmental impact of chemical industry. Reaction in water can be improved when microwave irradiation is applied to a synthetic procedure due to the possibility to reach temperatures higher than the boiling point. This is especially true when reactions are carried out in superheated/ subcritical conditions (over 100 °C). In this paper, several synthetic procedures that use superheated or subcritical water as solvent in sealed vials under microwave irradiation as heating system, are reviewed. Noteworthy, the targets of these synthesis are valuable compounds of pharmaceutical interest.

Research concerning green solvents is focused on reducing environmental damages due to the use of toxic solvents in organic chemistry. Hence, there have been developed a lot of solvent-free processes as well as more efficient recycling protocols in the last decades. Unfortunately, these approaches have their limitations. Therefore, the authors review different environmentally benign solvent alternatives. This report highlights reactions using water, fluorous solvents, ionic liquids, organic carbonates, supercritical carbon dioxide, as well as biosolvents instead of conventional organic solvents.

The use of biocatalysis for the provision of optically active building blocks and other useful compounds for fine chemicals and pharmaceutical industries is nowadays a mature technology. To further improve the ecological footprints of these applications, there is currently an increasing interest in using biomass-derived solvents for enzyme-catalyzed processes that may be implemented at industrial level on a midterm basis. The rationale behind these concepts would be the final replacement of petroleum-based solvents by more benign, environmentally-friendly, biodegradable, tunable and smart solvents. This review discusses the state-of-the-art on this topic, focusing on recent enzymatic applications reported in deep-eutectic-solvents, 2-methyltetrahydrofuran, glycerol-based solvents, and organic carbonates, among some important relevant cases of biomass-derived solvents from which biocatalytic applications have been assessed. When possible, the connection of these emerging applications with pharmaceutical chemistry will be provided as well. By looking at the topic from a whole-picture perspective, there are already an interesting number of proof-of-concept approaches that properly combine enzyme catalysis and bio-based solvents. Yet, the general impression is that the area is largely unexplored, with plenty of exciting opportunities, and therefore it may be certainly expected that new applications will be developed and reported in the coming years.

Chemistry and pharmacological activity of various types of Mannich bases and their derivatives were well documented. A survey of the literature revealed extensive studies on the synthesis and reactivity of Mannich bases derived from ketones, amides, enamines, phenols and indoles of widely different structures, while comparatively little attention has been given to Mannich bases derived from nitroalkanes and related nitrocompounds. Mannich reactions using nitroalkanes and related compounds as substrates are of synthetic relevance and the products are promising as biologically active substances. It is known that the nitro group is an important constituent of many biologically significant heterocycles such as antibiotic drugs (nitrofurantoin and nitrofurazone). A number of nitro-heterocycles of pharmacological interest were also synthesized by Mannich reactions with suitable nitro-substrates. In view of this, and because of the widespread and increasing interest in the chemistry of Mannich bases, the present work is concerned with attempts to extend the scope of Mannich reactions with nitroalkanes to include the synthesis of a variety of nitro N- and S-heterocycles.

This paper gives an overview of the available methods for racemization of amines and related derivatives, and the racemization catalysts can be coupled with enzymes to achieve the dynamic kinetic resolution, which provides enantiopure products with approximate 100% yields. Transition metal-catalyzed racemization, free radical-based racemization, racemase leading to automatic racemization and alkali-catalyzed racemization have been summarized, and their advantages and disadvantages have been discussed and compared. A purely enzymatic method would enable efficient and environmentally benign processes as a green and sustainable technique.