Current Organic Chemistry - Volume 6, Issue 3, 2002

A major fraction of the organic compounds isolated from nature are comprised of nitrogen, oxygen, or sulfur heterocycles. Nirogen-containing substances called alkaloids among them represent a majority of the important medicinal agents discovered in nature. The development of new synthetic methodology for the preparation of such alkaloids and the application of these methods to the synthesis of alkaloidal natural products continue to be an active and exciting area of research in organic chemistry. Especially, polyhydroxylated alkaloids possessing an azetidine-, pyrrolidine-, piperidine-, pyrrolizidine-, or indolizidine-ring structure have attracted a great deal of interest because of their applications from both a biological and a synthetic point of view. Since several reviews have already appeared concerning isolation, structural determination, total synthesis and biological aspects of these compounds independently, the scope of this review is to underline the most recent advances on the synthesis of monohydroxylated, dihydroxylated, and tri- or above hydroxylated bioligically active natural alkaloids containing the ring sturctures described above and related compounds according to those strategies involving prior construction of chiral pools (such as carbohydrates, amino acids, or tartaric acid)-derived crucial lactam intermediates suitable for further chemical elaboration.

β-Lactams (2-azetidinones) are one crucial structural element of the natural products with antibiotic properties. Since the introduction of penicillin into therapy, bacteria have developed an incredible and growing resistance to β-lactam antibiotics, essentially due to the hydrolytic ability of extremely active β-lactamases. The resistance of bacteria to the classical β-lactam antibiotics like penicillin and cephalosporin can be overcome, e.g., by using novel β-lactam moieties in drugs which show much higher stability towards these resistance bacteria. Furthermore, the recent discoveries of some azetidine-2-ones which display a broad range of enzyme-inhibitory activity justify a renewed interest in these compounds. Besides their significance as bioactive agents, the importance of β-lactams as synthetic intermediates have been widely recognized in organic synthesis. The 2-azetidinone skeleton has been extensively used as a template on which to build the carbo(hetero)cyclic structure fused to the four-membered ring, using the chirality and functionalization of the β-lactam ring as a stereocontrolling element. The present review will draw special attention to radical reactions, cycloaddition reactions (Diels-Alder, [2 + 2] cycloaddition reaction, and 1,3-dipolar cycloaddition), and transition metal-catalyzed reactions (Pauson-Khand reaction, ring closing metathesis and Pd-catalyzed cyclizations) as useful methods for the preparation of bi- and tricyclic-β-lactams with non-classical structure.

The number of publications that describe the development of novel molecular imprinted polymers (MIPs) has risen dramatically in recent years, demonstrating clearly the potential of this molecular recognition driven technique in a variety of separation-based and alternative technologies. This review covers the development of molecular imprinted polymers that have utilised biologically active substrates - in particular steroidal systems, as templates and then details the range of applications of these imprinted resins. The optimisation of molecular imprinting techniques for substrates of this type are described, starting from studies derived from early immunological theories, and concluding with coverage of state-of-the-art methods that are directed towards the next generation of MIPs

Resonance-stabilized carboxylic acids dienediolates result from O,C-deprotonations of α,β-unsaturated or β,γ-unsaturated carboxylic acids, the second deprotonation occurring easily, at an allylic position, than on saturated congeners. This π-extended enolates can react through their α or γ carbon atoms, leading to single or predominant compounds when allowed to react with electrophiles under adequate conditions. The ease of deprotonation of carboxylic acids permits for a range of bases and countercations to be employed, both factors altering the reactivity of ensuing dianions, and new conditions are described continuously. This versatile building blocks have this quality as an additional advantage, from an experimental point of view, that the products are easily isolated from the reaction mixture with high purity by means of a pH control in the reaction work up. This review tries to focus on the effort to control the regioselectivity, diastereoselectivity and enantioselectivity of the addition of dienediolates of carboxylic acids to different electrophiles. 2-Alkylbenzoic acids and their heterocyclic congeners have also been included as they may be considered as π-extended dianions, the second deprotonation occurring at a benzylic site. The aim of this review is to make the reader up to date with the recent and numerous developments in the use of dienediolates of carboxylic acids in synthesis. The period up to and including 1992 has been previously reviewed [1-4], most recently by Thompson [5, 6], and will not be covered in detail in this review.