Current Organic Chemistry - Volume 14, Issue 10, 2010

Dehydrogenases are amongst the most promising enzymes in biocatalysis, due to their ability to perform asymmetric and regioselective reductions of both ketones and double bonds. These enzymes need a soluble cofactor to perform their function, being NADH the most commonly used. On the other hand, the yields are determined by the equilibrium constant of the Redox reaction, making the use of a large excess of cofactor necessary to transform most of the substrate into product. Thus, the industrial implementation of these enzymes requires solving the cofactor recycling matter and the shifting of the equilibrium towards the desired product. There are currently several solutions for the recycling and reuse of Redox cofactors, but the coupling of two reactions catalyzed by dehydrogenases seems to be the most promising alternative. This implies in many instances the use of a second dehydrogenase, which reduces the oxidized cofactor (NAD+) and oxidizes a second substrate. This second substrate needs to be cheap and inert, and those that result in “irreversible” reactions are preferred (e.g., formate dehydrogenases), because that way the Redox reaction could be directed in the desired way, even using small concentrations of the cofactor. In this review, we will discuss different current methods for recycling NADH, especially those involving enzymes. The stability of the cofactor and new proposals to simplify reactor design (e.g., solid phase use of cofactors) will be commented. Special emphasis will be paid to the new tendencies in the design of “second enzymes” biocatalysts (new enzymes from thermophiles, new immobilization-stabilization protocols), that may solve some of the current problems derived from the low stability of the available enzymes.

The present work examines the relationship between the structure and chiroptical properties of penicillins and cephalosporins and their oxa- and carbaanalogues utilizing the electronic circular dichroism (CD). For some of the model compounds the study is additionally supported by the X-ray diffraction analysis. The applicability of the helicity rule that correlates the molecular structure of compounds and their CD spectra in respect to all classes of β-lactam derivatives is tested. It is demonstrated that a variety of oxacephams, clavams, and their carbaanalogues conform to the rule. To validate the experimental data the CD spectra computed using time-dependent density functional theory (TDDFT) are compared to the experimental curves recorded for the representative β-lactam derivatives. The study reveals a high sensitivity of the CD spectra to the configuration at the bridgehead atom and a surprisingly high sensitivity to the molecular conformation and substitution of the five- or six-membered ring. The results demonstrate that such a combined treatment permits the determination of the absolute configuration with high confidence.

The original Grunwald-Winstein equation (1948) involved the development of a scale of solvent ionizing power (Y). Subsequent work has refined this scale and involved the development of scales of solvent nucleophilicity (N) and a term to correct for deviations when aromatic rings are present, governed by the aromatic ring parameter (I). These three scales, and the sensitivities towards each, can be related to specific rates of solvolysis through linear free energy relationships (LFERs). One important area of application of LFERs has been to the solvolyses of tert-alkyl halides. It has been proposed that the solvolysis of tert-butyl chloride involves a nucleophilic component, although other workers have suggested that the effects observed are related to electrophilic not nucleophilic influences. Takeuchi (1997) studied a compound with two of the methyl groups of tert-butyl chloride replaced by neopentyl groups. For this highly-hindered substrate there was no evidence for nucleophilic participation. Liu (1998) and Takeuchi (2001) have reported concerning the solvolyses of additional significantly-hindered tertiary alkyl chlorides. Liu (2009) has presented a parallel study of bromides. Martins (2008) has considered hindered tertiary alkyl halides, mainly with carbon-carbon multiple bonds as substituents. It was proposed that the hI term was of importance, with the sensitivities (h) sometimes positive and sometimes negative. To explain negative values, it was suggested that the I scale might contain a nucleophilicity component. In this review, we bring together, with analysis and commentary, the work of Takeuchi, Liu, Martins and others concerning the solvolyses of tertiary alkyl halides, with emphasis on the relevance of the three scales that have been developed for use in Grunwald-Winstein correlations.

In this review paper we present the most important features of microwave irradiation, their physical characteristics and the properties upon an interaction with matter. The heating mechanisms are described, followed by a description of the available microwave equipment, including the differences between single- and multi-mode microwave reactors, considerations on open vs. closed reaction vessels, the selection of the appropriate solvents (or possible uses of solvent-free reaction conditions), the problems connected with scale-up, as well as the continuous flow processes and automation of microwave-assisted synthesis. A series of transformations of organic compounds with the emphasis on the conversion of heterocycles is presented. In the last part we present some of the most interesting properties of 2H-pyran-2-ones, their fused derivatives and other systems, including the synthesis of natural and other compounds incorporating this structural fragment and further transformations with a special emphasis on Diels-Alder cycloadditions. The research conducted in domestic microwave ovens is, due to the well-known problems associated with reproducibility, only partially included.

This paper highlights several methods of C-C and C-H transfer reactions in aqueous media. In all cases, thiols play the role of the reducing agents. A variety of useful synthetic methodologies were also described, which occurred mainly via a free radical non-chain transfer processes. The potential usefulness of free radical reactions in water is demonstrated by ever-increasing studies over the last 5 years. In addition, a cis-trans lipid isomerization process under photoand gamma-irradiation conditions was reported. The complexity of the selective generation of thiyl radical in aqueous media and/or in biological milieus makes this topic highly important in chemistry, biology and medicine.