seco-Cyclothialidines are a promising class of bacterial DNA gyrase B subunit inhibitors. A new seco-cyclothialidine derivative containing a dioxazine moiety, BAY 50-7952, was synthesized through a new concise pathway. One key step of the synthesis is the straightforward formation of the 2-aminothiazole derivative of S-tritylcysteine. In biological tests, BAY 50-7952 and other known seco-cyclothialidines exhibited high and selective activity toward bacterial DNA gyrase and toward Gram-positive bacteria. The dioxazine moiety and other similar groups were found to be important for the ability of the seco-cyclothialidines to penetrate bacterial membranes. The opposite enantiomer ((S)-form) of BAY 50-7952 was also synthesized, and neither significant target activity nor in vitro antibacterial activity were found, suggesting a highly selective fit of the (R)-form. Despite promising in vitro activity, only poor activity was found in the murine infection model.

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PeptidesPeptides U 0400 Improved Procedure for the Synthesis of Thiazolium-Type Peptide Coupling Reagents: BMTB as a New Efficient Reagent. -A new strategy for the large-scale preparation of peptide coupling reagents (I) is developed. Compared to other agents, (Ib) demonstrates higher conversion rates in the difficult model coupling of the amino acids (II) and (III). -(WISCHNAT*, R.; RUDOLPH, J.; HANKE, R.; KAESE, R.; MAY, A.; THEIS, H.; ZUTHER, U.; Tetrahedron Lett. 44 (2003) 23, 4393-4394; Pharma-Forschungszent.,