Saturday, February 16, 2008

Novel Reactions: Are anymore waiting to be Discovered?

Inspired by Barton's landmark total synthesis of Usnic acid, a method was devised by Baran for the direct oxidative coupling of indoles and pyrroles to a range of carbonyl compounds. ( Baran et al, J. Am. Chem. Soc. 2007, 129, 12857-69 )

when one examines the piece of work to which such a description has been applied it often turns out to contains only a minor improvement on a well known reaction or a new application of old technique.

Saturday, February 2, 2008

F in Drug Discovery

The importance of Fluorine in medicinal chemistry is well recognized. Indeed, an increasing number of drugs on the market contain Fluorine, the presence which often is of major importance to activity. A recent review article (Chem. Soc. Rev., 2008, 37, 320) by Sophie Purser describes the role of Fluorine in medicinal chemistry.

Substitution of H by F can profoundly change the conformational preferences of small molecules because of small size and streoelectronic effects.
F can enhance binding efficasy and selectivity in pharmaceuticals.
F substituents on ligands prefer to orient toward electropositive regions of receptor sites.
Distinct fluorofilic environment in proteins include the ubiquitous peptide bonds, which undergo multipolar C-F…H-N, C-F..C=O and C-F..H-C interaction.

Systematic fluorine scans of ligands as a promising strategy in lead optimization, not only to enhance physicochemical and adsorption, distribution, metabolism, and excretion properties, but also to strengthen protein-ligand binding interaction.

The effects of Fluorine substitution expands, further applications in drug discovery will emerge.Modern Fluorine Organic chemistry has dramatically widened the synthetic repetoire for the specific introduction of F in the organic molecule.