Solution-Phase Parallel Synthesis of 115 Homosilatecan Analogues

摘要

The parallel synthesis of 115 homosilatecans on 1-5 mg scale has been accomplished. Key reactions include N-proparylation of a common iodopyridione lactone with a silyl-substituted propargyl bromide, followed by cascade radical annulation with a substituted isonitrile. Simple manual techniques for parallel reactions were coupled with automated purifications (SPE, HPLC) to give high-purity final products. The speed and simplicity of the automated purification protocol more than compensated for yield losses in the synthesis of some analogues relative to traditional flash chromatographic purifications.