LIBRARY GENERATION THROUGH SUCCESSIVE SUBSTITUTION OF TRICHLOROTRIAZINE

The decreasing reactivity of tri-, di- and monochlorotriazine was util ized for the solid-phase construction of a combinatorial library with three randomized positions, using 20 amino acids and 50 amines as buil ding blocks. The first chlorine atom was selectively substituted by co upling a large excess of trichlorotriazine to the support-bound amino acid, thus avoiding simultaneous substitution of the second chlorine. The second and third diversity positions were selectively introduced b y coupling amines at different temperatures. Mixtures of model compoun ds were synthesized and analyzed, showing the correct representation o f all expected components. A library composed of 12 000 compounds was generated using this method.