Formaldehyde-a key monad of the biomolecular system.

Experiments will be presented and reviewed to support the hypothesis that the intrinsic reactivity of formaldehyde may lead to the formation of a rather comprehensive set of defined biomolecules, including D-glucose, thus fostering concepts of evolution considering the existence of a premetabolic system as a primordial step in the generation of life.

Synthesis and pharmacological characterization of beta2-adrenergic agonist enantiomers: zilpaterol.

The beta-adrenergic agonist 1 (zilpaterol) is used as production enhancer in cattle. Binding experiments of separated enantiomers on recombinant human beta(2)-adrenergic and mu-opioid receptors and functional studies showed that the (-)-1 enantiomer accounts for essentially all the beta(2)-adrenergic agonist activity and that it exhibits less affinity toward the mu-opioid receptor than (+)-1, which is a mu-opioid receptor antagonist. X-ray crystallography revealed the absolute configuration of (-)-1 to be 6R,7R.

Taste, a new incentive to switch to (R)-praziquantel in schistosomiasis treatment.

BACKGROUND: Praziquantel (PZQ) is the drug compound of choice in the control and treatment of schistosomiasis. PZQ is administered as a racemate, i. e. 1ratio1 mixture of enantiomers. The schistosomicidal activity arises from one PZQ-enantiomer, whereas the other enantiomer does not contribute to the activity. The WHO's Special Programme for Research and Training in Tropical Diseases (TDR) has assigned the low-cost preparation of pure schistosomicidal (-)-PZQ a key priority for future R&D on PZQ, but so far this transition has not happened. PZQ has two major administration drawbacks, the first being the high dose needed, and its well documented bitter and disgusting taste. Attempts of taste-masking by low-cost means have not been successful. We hypothesized that the non-schistosomicidal component in PZQ would be the main contributor to the unpleasant taste of the drug. If the hypothesis was confirmed, the two major administration drawbacks of PZQ, the high dose needed and its bitter taste, could be addressed in one go by removing the component contributing to the bitter taste. METHODS AND FINDINGS: PZQ was separated into its schistosomicidal and the non-schistosomicidal component, the absolute stereochemical configuration of (-)-PZQ was determined to be (R)-PZQ by X-ray crystallography, and the extent of bitterness was determined for regular racemic PZQ and the schistosomicidal component in a taste study in humans. FINDING: The schistosomicidal component alone is significantly less bitter than regular, racemic PZQ. CONCLUSION: Our hypothesis is confirmed. We propose to use only the pure schistosomicidal component of PZQ, offering the advantage of halving the dose and expectedly improving the compliance due to the removal of the bitter taste. Therefore, (R)-PZQ should be specifically suitable for the treatment of school-age children against schistosomiasis. With this finding, we would like to offer an additional incentive to the TDR's recommendation to switch to the pure schistosomicidal (R)-PZQ.

(2R,3S)-(+)- and (2S,3R)-(-)-Halofuginone lactate: synthesis, absolute configuration, and activity against Cryptosporidium parvum.

The trans-enantiomers of the commercially important anti-protozoal compound Halofuginone have been prepared and characterized, and the absolute configuration was assigned by X-ray crystallography. The activity of both enantiomers against Cryptosporidium parvum was determined in vitro and related to acute toxicity in vivo. It was shown that both the activity and the toxicity are properties of the (2R,3S)-enantiomer. We conclude that with respect to broadening the therapeutic window there is no advantage in application of one enantiomer over the application of the racemic mixture in the treatment of C. parvum infections.

1,17-Diphenyl-2,4,6,8,10,12,14,16-octaoxaheptadecane.

The title compound, C(21)H(28)O(8), crystallizes with two independent molecules, each with a crystallographic twofold axis passing through the central CH(2) group. The two molecules have different orientations of the terminal benzyl groups. The average C-O bond length in the polyoxymethylene helix, corrected for librational motion, is 1.419 A. The molecules are connected into layers by intermolecular C-H...O and C-H...pi(phenyl) interactions.