Synthesis and biological evaluation of cis-restrained carbocyclic combretastatin A-4 analogs: Influence of the ring size and saturation on cytotoxic properties.

Combretastatin A-4 (CA-4) is a highly cytotoxic natural product and several derivatives have been prepared which underwent clinical trial. These investigations revealed that the cis-stilbene moiety of the natural product is prone to undergo cis/trans isomerization under physiological conditions, reducing the overall activity of the drug candidates. Herein, we report the preparation of cis-restrained carbocyclic analogs of CA-4.

Chiral hydroxylation at the mononuclear nonheme Fe(II) center of 4-(S) hydroxymandelate synthase--a structure-activity relationship analysis.

(S)-Hydroxymandelate synthase (Hms) is a nonheme Fe(II) dependent dioxygenase that catalyzes the oxidation of 4-hydroxyphenylpyruvate to (S)-4-hydroxymandelate by molecular oxygen. In this work, the substrate promiscuity of Hms is characterized in order to assess its potential for the biosynthesis of chiral α-hydroxy acids. Enzyme kinetic analyses, the characterization of product spectra, quantitative structure activity relationship (QSAR) analyses and in silico docking studies are used to characterize the impact of substrate properties on particular steps of catalysis.

Gram scale de novo synthesis of 2,4-diacetamido-2,4,6-trideoxy-D-galactose.

In contrast to the infection with Gram-negative bacteria, the precise mechanism of infection with their Gram-positive counterparts is still poorly understood. It has been established, that teichoic and lipoteichoic acids play an important role in host-pathogen interaction. The bacterium Streptococcus pneumoniae is one of the severe life-threatening Gram-positive pathogens and elucidation of the structure of its lipoteichoic acid revealed 2,4-diacetamido-2,4,6-trideoxy-d-galactose as a main component of the cell wall glycopolymer.