By Hadley Gavin
The customchemical synthesis in the pharmaceutical research represents the simultaneous, automated synthesisand purification of up to 200 test compounds. This working method allows themedical chemist access to a multiple of structure-activity information over theclassical synthesis of individual compounds over the same period of time andwith comparable effort. The parallel synthesis thus contributes significantlyto the shortening of the optimization phase of new active ingredient.
Since not every single reaction is individually monitored and optimized in parallel synthesis, the hit rate of desired target molecules is expected to be somewhat lower than in the classical single synthesis of compounds. The same applies to the purity of the products obtained. Therefore it is automated, through portable cleaning processes such as automated HPLC fractionation, the so-called parallel cleaning, play a key role.
The combination of parallel syntheses and parallel cleaning results in an impressive increase in efficiency:
That it does matter whether a chiral drug molecule – that is, one that can occur in two mirror-image forms – in its R (rectus, Latin right) or in its S-form (sinister, Latin left) is present, since at least since Thalidomide or scandal of the 60s known. While the R-form of thalidomide has a sedative effect, the S-form is responsible for the teratogenic damage. The synthetic route used by the chemists at that time produces a mixture, a racemate, of both products. Today, on the other hand, efforts are being made to find ways of chiral agents to separate them in pure form after synthesis – or to find synthetic routes that yield only a single enantiomer as a product.
- “The reaction is a linkage between an inamide (a compound bearing a nitrogen atom adjacent to a carbon-carbon triple bond) and a sulfoxide (in which a sulfur and oxygen sulfinyl group is attached to two carbon atoms) using a strong acid as Catalyst, “explains Maulide.”
- The whole thing takes place at room temperature in a conventional solvent. The catalyst is regenerated at the end of each cycle. “This is a waste-free chemistry, says Maulide. There is only one reaction product and there are no by-products or waste products.
- “And the trick in our reaction is that we can use a chiral sulfoxide. The chirality is not with a carbon atom as usual, but with the sulfur of the sulfoxide. This stereo information is then transferred almost directly to the carbon of the product. “
Carbohydrates are complex molecules whose production poses a real challenge for the synthetic chemist. This fact is a major reason that these important biomolecules have been much less studied than other biomolecules such as nucleic acids and peptides. The present article discusses the automated chemical synthesis of sugar molecules and their importance and scope in the overall glycopeptide research.
