Current Organic Chemistry - Volume 14, Issue 20, 2010

The 2010 Catalysis/Natural Product Chemistry issue of Current Organic Chemistry contains four contributions from eminent scientists in different fields. The first review, written by María J. Hernaiz and coworkers focused on recent progress in the field of “Biocatalysis in Green Solvents”. There has been a variety of attempts to explore the properties of green solvents in combination with biocatalysis wich has led to development of a range of efficient organic reactions. Alcantara and coworkers provided an overview of the use of supported reagents on inorganic carriers such as Celite in organic synthesis Professor Penoni and coworkers illustrated the recent synthetic approch for the preparation of indoles. The interest of authors is particularly focused on the indolization procedures and the different procedures for ring closure. Finally Santi and his group provided an overview of recent results concerning the use of organoselenium compounds in new organic synthetic procedures. Finally, as a guest editor for this specially issue, I would like to express my sincere thanks to all the Authors for providing these articles and for the fascinating results described.

During the past decade there has been increasing interest in the use of biocatalysts (enzymes or cells) for the transformation of synthetic or natural materials with high selectivity (chemo-, regio- and stereoselectivity). At least three advantageous features have contributed to the development of biocatalytic processes. In the first place, relatively mild reaction conditions are sufficient to run enzyme-catalysed reactions; this feature reduces energy requirements. In addition, environmental safety and cleanliness due to the use of low salt and low metal concentrations, together with a decreased of by-product formation, contribute to achieve environmentally friendly processes. Secondly, the importance of chirality in the efficiency of many drugs and the stereochemical properties of biocatalysts have led to the development of excellent biocatalyst useful in asymmetric synthesis. Some of these novel and versatile biocatalysts are obtained by mutagenesis and directed evolution. Both types of research require accurate and fast methods to choose the right stereoselective biocatalysts. Lastly the area of biocatalysis in nonaqueous media has grown immensely over the last few decades since it was proven that most enzymes can function extremely well under anhydrous conditions, displaying a number of useful properties such as enhanced stability and different substrate selectivity. Therefore, the search for new environmentally benign solvents and biocatalyst that operate efficiently in them and can be easily recycled is of significant industrial interest. Recently, there has been a variety of attempts to exploit some of the properties of green solvents in combination with the benefits of using biocatalysts to develop cleaner synthetic processes, and these are discussed in this review, focusing mainly on the application of hydrolases (proteases, lipases and glycosidases) in industrial processes.

The use of reagents supported on inorganic carriers is becoming increasingly more common due to their high efficiency, which is mainly caused by a combination of several factors: a) an increase in the effective surface area for reaction; b) the presence of pores which constrain both substrate and reactant, thus lowering the activation entropy of the reaction; c) a synergism (for displacement reactions) resulting from bringing electrophiles and nucleophiles into proximity. Thus, organic reactions can be carried out cleanly, rapidly and in high yield under mild conditions. In this context, the diatomaceous earth Celite has been successfully employed to support a plethora of reagents, ranging from alkali fluorides (which allow to attain high chemoselective (hetero) atom (N, O, S) functionalization protocols, as well as Michael additions, nucleophilic aromatic substitution or organotin waste product removal), to oxidant agents (such as silver carbonate or chromium trioxide, in order to promote mild oxidations), as well as dehydrating agents (such as DCC). The absence of any chemical reactivity of this support is compatible with high functionalized molecules, therefore constituting a suitable methodology to modulate the reactivity of the effective reagent. Furthermore, the application of Celite-supported enzymes is a well known strategy for performing regio and/or stereoselective biotransformations; in fact, this easy immobilization technique allows the preparation of highly stable and active biocatalysts for many synthetic applications. Thus, in this paper we will present an overview of the use of Celite-supported reagents, both organic molecules and biocatalysts, in organic chemistry and biotransformations.

The present review is devoted to illustrate the state of the art of the syntheses of indoles, focusing particularly on the most recent developments of new synthetic approaches. Emphasis is given to the preparation of natural products or bioactive compounds containing the indole unit. We present a historical perspective of indole synthesis showing the strategies by choosing the nitrogen precursors. The review is organized sharing the indole synthetic approaches by using different nitrogen-containing functional groups in aromatic substrates used as source of the nitrogen of the indole moiety. Some functional groups and some typical reactions are particularly stressed and highlighted because of the limited coverage given in previous reviews published on this topic. Other synthetic approaches more used and discussed in recent, complete and excellent reviews on the topic are summarized but the most recent published results are highlighted. Our interest is particularly focused on the indolization procedures and on the different methods used for the ring closure and no attention is given to modification of indole structures starting from molecules with a preformed indole unit. Intriguing indole syntheses are continually discovered and the importance that the scientific community gives to these new developments is connected with the strategic role of molecules containing the indole unit. Indoles are the class of heterocycles with more applications and extensive interest due to their biological and pharmacological activity.

The importance of selenium as essential trace element is today generally recognized. The major biological form of this element is represented by the selenocysteine, incorporated into certain protein having redox motifs. Selenoenzymes are known to catalyze in nature the reduction of peroxides (gluthathione peroxidase) as well the selective deiodination of iodothyronine (iodothyronine deiodinase) and the reduction of dithiol-disulfides (thioredoxin reductase). A variety of organoselenium compounds have been proven to be useful for organic synthesis over several decades. Organoselenium species can be introduced as either nucleophiles or electrophiles to other organic molecules, producing useful intermediates for organic synthesis. Optically active organoselenium derivatives and their application to highly selective asymmetric synthesis are also of current interest. Probably the most interesting aspect, which emerged in recent years, concerns the possibility of effecting some functional group conversions using catalytic amounts of the electrophilic selenium reagent or using selenium containing compounds as chiral ligands in metal catalyzed reactions. The developments of all these catalytic processes probably represent the most important results which have been reported recently in this field. Their conceptual and synthetic relevance considerably increases the importance of organoselenium chemistry and are here reviewed.

The purine ring is undoubtedly among the most ubiquitous of all the heterocyclic compounds. This arises not only from the universal occurrence of adenine and guanine in DNA and RNA and of additional modified derivatives in the various tRNAs but also from the subsidiary uses of the ring system in a great number of biochemical systems. The development of new methods for metal-mediated coupling with aryl or heteroaryl halide substrates has expanded the range of synthetically accessible arylpurine derivatives. Aryl boronic acids have proved to be extremely available reagents for metal-mediated C-C and C-N coupling reactions. Coupling reactions resulting in C-C bond formation are catalyzed by palladium and nickel catalysts at positions C2, C6 and C8. The reactivity at C6 position has been demonstrated using fluoro-, chloro-, bromo-, iodo-, sulfanyl, sulfonyl, sulfonyloxy- and azole-substrates. The ease of obtaining the activated purine substrates is an important factor when selecting appropriate coupling conditions. Copper-mediated N-arylations occur at positions N7 and N9. These methods are also applicable using solid-supported purine substrates and provide convenient access to structurally unique derivatives with applications in drug discovery. Continuing advances in this field can be expected to result through improved mechanistic understanding and the development of new catalysts and ligands.

Due to the relevant biological role of sphingosines, ceramides and glycosyl ceramides, and the increasing demand of these compounds for biological evaluations, developing methods targeting sphingosine and phytosphingosine and derivatives have attracted the interest of researchers. The review initially presents the structural features of these compounds, presenting the different types of nomenclature of phytosphingosines, and the more relevant biological properties, as well as the biochemical synthesis. The synthetic procedures using products of the chiral pool, mainly carbohydrates and serine derivatives, are progressively shifted by asymmetric synthesis procedures, and particularly to those based on catalytic reactions. In this way, the review presents separately the synthetic procedures leading to sphingosine and phytosphingosine, and each case the synthesis based on the chiral pool are presented separately from the asymmetric synthesis. In this last case the methods are classified depending of the strategy used for inducing chirality, chiral auxiliary, chiral reagent or catalytic procedures, to which special attention is devoted. The syntheses are discussed in detail and reagents and yields for each step are provided. The review also rationalizes and integrates the different synthetic procedures from the point of view of construction the chiral fragment of these molecules.

4-(Aryl)-6-pyridin-3-yl-1H-pyrazolo[3,4-b]pyridin-3-amines were reacted with dimethylformamide-dimethylacetal to give the corresponding pyrazolopyridin-3-yl-imidoformamides which in turn, reacted with malononitrile or 2-cyanoethanethioamide and ethyl cyanoacetate to give the corresponding pyridopyrazolo-pyrimidines. Also, they reacted with active halogen-containing compounds to give the corresponding imidazopyrazolopyridin-2-amines and pyrazolopyridin-2-yl-1-aryl-ethanones. The structures of all newly synthesized heterocyclic compounds were elucidated by considering the data of elemental analyses, IR, 1H NMR and mass spectrometry. All newly synthesized heterocyclic compounds were tested as anti-Alzheimer and anti COX-2 reagents and exhibited promising results.

The selective introduction of a boron unit in an organic framework opens new perspectives in both building block design and functionalization protocols. The presence of carbonyl or imino groups in β position with regard to the boryl moiety makes them suitable organoboron intermediates for difunctionalized purposes. Catalytic synthetic methodologies have recently been developed to introduce a boryl group at the β- position of α,β-unsaturated esters, ketones, aldehydes, amides, nitriles, as well as imines and oximes. The asymmetric version favours the chiral Cβ-B formation which can be eventually transformed into useful alcohols or acetyl functional groups. Alternatively, β-boronate carbonyl or imino compounds can be prepared via alkylation of an enolate with α-haloboronates esters. The subsequent route for the preparation of the chiral β-boronate derivatives required transesterification protocols that successfully provided a series of β-oximo boronates, β-imino boronates and β-carbonyl boronates, with chiral boryl units. This review will enable the reader to understand catalytic and non-catalytic routes for the synthesis of β-boronate carbonyl and imino compounds. The overall mechanistic insights and the perceptible influence of additives on these different synthetic processes, will be discussed. More emphasis will be placed on further applications of the β-boronate compounds in the synthesis of diols or aminoalcohols, in particular where β-chiral centres efficiently control further enantioselective transformation, despite their remote position.

This review covers recent advances in the preparation and diverse chemistry of various types of bimetallic reagents derived from organoboranes. 1,1-Bimetallics containing lithium, zinc and zirconium were most extensively investigated among metalated alkyl and alkenylboranes. Recently, there is a significant progress in the chemistry of metalated arylboron derivatives such as lithiated and magnesiated arylboronic esters and related complexes. All these reagents were effectively used as intermediates in the synthesis of more elaborated organoboranes and functionalized organic compounds. Selected systems were designed as potential bidentate Lewis acids for anion sensing.