Joachim Rudolph

Facile Access to N-Thiazolyl α-Amino Acids from α-Bromo Ketones and α-Amino Acids

Abstract N-Substituted 2-aminothiazoles are synthesized in a one-pot procedure using readily available α-bromo ketones and amines. This method is compatible with a wide range of functional groups and offers a facile and efficient access to the class of N-thiazolyl α-amino acid derivatives.

Triphosgene as Peptide Coupling Reagent: Highly Efficient Total Synthesis of Cyclosporin O

Cyclosporins are immunosuppressive cyclic peptides from Cylindrocarpon lucidum Booth and Tolypocladium inflatum Gems. Cyclosporin A (CsA, Sandimmune) is a widely used drug for preventing the rejection of transplanted organs and for therapy of autoimmune diseases. The synthesis of cyclosporins is problematic due to their high content of N-methylated amino acids. We developed a highly efficient, racemization free solid phase synthesis of Cyclosporin O (CsO) using a combination of HOAt/DIC couplings and a novel, modified form of a recently described triphosgene coupling [1]. The latter was adapted for the synthesis of peptides with free carboxy terminus on highly acid labile TCP resin (trityl chloride polystyrene resin) using a specific combination of bases for activation and coupling at room temperature.