A Concise Synthesis of Silanediol-Based Transition-State Isostere Inhibitors of Proteases

<UFIGR ID="ol026195sn00002">An efficient synthesis of silanediol-based transition-state inhibitors of proteases is described. A new convergent synthesis has been optimized by using a two-step sequence of hydrosilylation followed by the addition of a silyllithio species to an imine. The method should be applicable to the synthesis of a wide variety of silanediol isosteres to probe the utility of this unique transition-state isostere.