THE SOLID-PHASE COMBINATORIAL SYNTHESIS OF BETA-THIOKETONES

A solid-phase split-mix organic synthesis method was developed which, by two synthetic steps, converts polymer-bound aldehyde I into resins III. Step one consists of dividing I into three equal portions in sepa rate flasks, condensing each with a different ylide, and subsequently recombining to give II. This mixture of beads was again equally divide d into three flasks, and each flask treated with a thiolate Michael do nor. Prior to recombining the contents of each flask (i.e., sub-librar y), samples of each resin were removed and incubated with a THF/HCO2H mixture to liberate the small molecule products. GC-MS established tha t each sub-library (A, B, and C) contained the three anticipated forma te esters. In addition, GC analysis illustrates that, while there were no purification steps involved in this solid-phase analogous organic synthesis save bead washings between steps, the desired products are o btained in excellent purity. Single bead (200-400 mesh) selection from library D (combined sub-libraries A-C), solvolysis, and GC-MS analysi s shows that compound identities can be established on a per bead basi s. (C) 1997 Published by Elsevier Science Ltd.