Current Organic Chemistry - Volume 9, Issue 4, 2005

The fact that many enzymes have broad substrate specificity has been a property of fundamental importance for the widespread applications of enzymes in synthetic chemistry. Many enzymes can, in addition, catalyze completely different reactions compared to their natural ones. The possibility of using molecular biology techniques to control such catalytic plasticity of enzymes in order to establish completely new reaction specificity in the active site is the topic for this review. The examples are subdivided according to six different approaches used (i - vi) for engineering of the reaction specificity. The first approach (i) is the random method of directed evolution to achieve new reaction specificity. Other approaches involve strategies where the reaction specificity of a known enzyme is implemented into another, closely related, enzyme by substituting key amino acid residues selected either by (ii) sequence or (iii) structural overlap of the two enzymes. Yet other approaches involve substitution of key amino acid residues to introduce new reaction specificity without comparing with a template enzyme (iv) and the introduction of a complete catalytic machinery (v). The final approach is the introduction of an active site into a non-catalytic protein (vi). These six different approaches for altering the reaction chemistry of enzymes each represent a powerful tool for controlling the catalytic plasticity of enzymes. The prospect for these altered enzymes as catalysts in synthetic chemistry is very large although examples of practical use are rare and still challenging. The progress in the area of altering enzyme reaction specificity will result in a continued development towards the goal of creating tailor-made enzymes for synthetic chemistry.

The present review intends to give an overview on the synthetic methods applied for the preparation of resorcarenes and all the conformation implications due to the flexibility of the target tetramers. The flexible resorcarenes can be rigidified by intramolecular bridging of adjacent oxygens with bifunctional reagents, to give cavitands. These compounds, which feature rigid bowl shaped cavities of different size and dimensions, depending on the bridging groups employed, will be examined according to these latter. Moreover, some emphasis will be placed in resorcarenes chirality and on the ways how to introduce it: either indirectly, e.g. by tetramerization of monomers containing a chiral center, or directly, by synthesis of macrocycles featuring a Cn-type symmetry, which is defined as inherent chirality and arises from the nonplanarity of the basic metacyclophane system. Finally, the use of resorcarenes as pseudo stationary phases for the separation of isomeric compounds will be mentioned.

Hydrazinoalcohols are versatile di- or trifunctional compounds with wide-ranging possibilities for application in organic synthesis. Numerous methods have been devised for the preparation of this family of compounds in recent decades. This review discusses the main pathways for the synthesis of hydrazinoalcohol derivatives, including epoxide ring-openings and nucleophilic substitutions by hydrazines, addition reactions to hydroxyhydrazones, hydrazine additions to olefinic bonds, electrophilic C- and N-amination reactions, cycloadditions, reductions of N-nitroso aminoalcohols and some unique procedures. The latest developments in these fields, involving both conventional and enzymatic catalytic methods of synthetic organic chemistry, allow the highly regio-, stereo- and enantioselective preparation of hydrazinoalcohol derivatives.

The 2,3-dihydro-1,4-benzodioxin structure is present in compounds having some interesting biological properties. The first access to this structure, performed from 2-alkyl-1,4-benzodioxin or benzene-1,2-diol via stoechiometric cyclization, generally gave mixtures of products. Recently, the organometallic-catalyzed synthesis of this structure was performed using mercuric oxide, or more interesting, palladium as the catalyst. The palladiumcatalyzed heteroannulation of various monoprop-2-ynylated catechol and aryl iodides in the presence of PdCl2(PPh3)2 and CuI afforded the corresponding 1-alkylidene or 1-arylidene-2,3-dihydro-1,4-benzodioxins in excellent chemical yields. However the palladium-catalyzed cyclisation of substituted benzene-1,2-diols with different propargylic carbonates gave the corresponding 1-alkylidene or 1-arylidene-2,3-dihydro-1,4-benzodioxins eventually substituted at position 2 by an aryl or an alkyl group. Moreover, this later methodology seems very powerful since it is possible to perform this heteroannulation in an asymmetric way in order to obtain the 1-alkyl- 2-alkylidene-2,3-dihydro-1,4-benzodioxins in enantioselectivities up to 96%.

This review attempts to systematize the myriad aspects of natural radioprotective agents assembled from a comprehensive survey. These aspects include definition, historical background, mechanism of action, components of biological system damaged by radiation, areas of application, classification, sources, activity profiles of radioprotective agents belonging to various classes exerting both prophylactic / therapeutic effects and finally, the combination strategies employed for enhancing radioprotective action and reducing toxicities. Some useful conclusions follow the main text. Future prospects in the area of natural radioprotectors are briefly touched upon at the end of the review.