A novel thiolate mediated cyclization to OPC-15161

An efficient synthetic route to OPC-15161 (1) was developed via novel pyraz ine ring closure promoted by a lithium thiolate anion. The key intermediate (4) was prepared in a one-pot procedure by treating the methyl ester (2) w ith a lithium arylthiolate. This protocol does not require a free acid inte rmediate and thus can establish the shortest route to pyrazine dioxide skel eton from tryptophan ester derivatives. In the present transformation, lith ium arylthiolates could behave like aluminium arylthiolates, and not like l ithium alkyithiolates that often cleave esters to the corresponding acids. One-pot reactions that involve lengthy multiple steps in a single flask are of significant importance in contemporary organic synthesis. Utilization o f a catalytic or stoichiometric promoter which can facilitate several trans formations is a key to the success of such reactions. In this paper, we wou ld like to disclose an interesting one-pot transformation discovered in our process research, which offered us novel information on the reactivity of metal thiolates. Main feature of our one-pot process is a merged deprotecti on-cyclization sequence. (C) 2000 Elsevier Science Ltd. All rights reserved .