Current Organic Chemistry - Volume 8, Issue 10, 2004

I am please to once again be serving as the executive guest editor for Current Organic Chemistry's issue on molecular recognition. This volume will cover a wide range of topics related to molecular recognition ranging from small molecules to biomacromolecules. As usual I would like to thank all of the authors and the editorial staff for making this issue possible. The first review in this volume is a contribution from Ronald K. Castellano (University of Florida). Prof. Castellano has conducted an extensive and through study into the nature of the C-H---O interaction and its role in molecular recognition. Professor S. B Shuker (Georgia Institute of Technology) along with co-authors R.E. Brewster, K. L. Caran and J.S. Sasine reports on the use of a novel family of compounds, the peptidocalixarenes, in molecular recognition processes. A more biological look at molecular recognition if offered in the final review form Prof. John Barbaro (University of Florida) who has written a nice review on carbohydrate based molecular recognition.

Recent studies confirm that C-H...O hydrogen bonds have many, if not all, of the spectroscopic and physical earmarks of “traditional” H-bonds. Only more recently have we come to understand that these contacts are operative not only in protein-protein recognition, but enzyme-substrate interactions (with implications for drug design), biological and nonbiological transition state stabilization and have, in some circumstances, a strength and geometric predictability to make them useful in the construction of materials and supramolecular assemblies. Forays into each of these areas have come largely due to advances in computational protocols and spectroscopic instrumentation. This review discusses the most recent findings related to the nature (i.e. strength, geometrical preferences, and spectroscopic features) and function (i.e. in supramolecular design and synthesis, conformational control, enantioselective synthesis, and biology) of C-H...O interactions in a variety of chemical and biological systems. An understanding of the key features of these interactions should promote their deployment in target areas like medicinal chemistry and materials science.

Calix[4]arenes have been extensively studied for their ability to act as synthetic receptors for metal ions and small molecules and, more recently, for use as enzyme mimics and molecular capsules. While the literature on substituted calixarenes is extensive, calixarenes that are substituted with amino acids and peptides-i.e., peptidocalixarenes-have received relatively little attention. The use of peptidocalixarenes as hosts is attractive because of the chirality and range of functional groups provided by amino acids. Calixarenes containing amino acids at the upper rim, at the lower rim or incorporated into the macrocycle have been prepared and many of these molecules have been investigated for their molecular recognition properties. Peptidocalixarenes have been demonstrated to bind small, organic molecules and metals, with high selectivity in some cases. In particular, stereoselectivity has been observed for the interaction of peptidocalixarenes with chiral molecules. Peptidocalixarenes that bind to proteins and disrupt proteinprotein interactions have also been reported. This review describes the work that has been reported to date on the synthesis and properties of peptidocalixarenes. These recent and exciting results in calixarene chemistry lay the foundation for future developments in the application of peptidocalixarenes to significant research problems in molecular recognition chemistry.

The recognition of glycoprotein ligands by the selectins mediates leukocyte recruitment during an inflammatory response. Mimetics whose designs are based on the sialyl Lewis-x tetrasaccharide, common to these glycoproteins, have proven to be good inhibitors of leukocyte binding to the selectins. Some of the more recent approaches to the synthesis of these mimetics, including the use of polymeric and liposomal displays, multicomponent condensation reactions, and solid-phase peptide synthesis, are presented.

Microwave Assisted Organic Synthesis is known for the spectacular accelerations produced in many reactions as a consequence of heating rates that cannot be reproduced by classical heating. As a result, higher yields, milder reaction conditions and shorter reaction times can be achieved and many processes can be improved. Furthermore, reactions that do not occur by conventional heating can often be carried out under the action of microwaves. This effect is particularly important in the preparation of isotopically labeled drugs with short halflives (11C, t1 / 2 = 20 min.; 122I, t1 / 2 = 3.6 min. and 18F, t1 / 2 = 100 min.) and high throughput chemistry (combinatorial chemistry and parallel synthesis). Another very important application of microwave irradiation involves the modification of the selectivity (chemo-, regio- and stereoselectivity) in relation to conventional heating. Selectivity is a crucial objective in organic synthesis and is usually achieved by selecting the appropriate reaction conditions, solvent, temperature, time or using kinetic vs. thermodynamic control, protection and activation and selective catalysts. The ability to control the selectivity by simply choosing the appropriate mode of heating (conventional vs. microwaves) is very attractive proposition. However, the effect of microwave irradiation still needs to be rationalized in order to predict the effect of the radiation on the selectivity of a given reaction.

The review will focus on the recent progress achieved in the palladium-catalyzed oxidative carbonylation reactions of unsaturated substrates that has allowed the development of new, efficient and selective syntheses of a variety of carbonyl compounds. Coverage: until the end of 2002.