Structure based library approach to photosynthesis inhibitors: Combinatorial synthesis of hydrouracil library

Based on the binding mode for hydrouracil in photosystem II (PS II) D1 protein, a general method for the solid phase combinatorial synthesis of hydrouracil library was developed. The acryloyl chloride or acid were coupled to Wang resin 1 to afford the acryloyl ester 2. Resin bound ester 2 reacted with various primary amines to give secondary amines 3, which were converted to the resin bound ureas 4 by treatment with isocyanates. Preparation of the hydrouracils 5 was achieved by the acidic cyclization-cleavage from the resin. For characterization purposes, 8 hydrouracil analogues were synthesized in parallel, following which a small library of 9 hydrouracil derivatives was prepared after cleavage from Wang resin. All the 9 bydrouracil derivatives desired were identified by GC-MS.