Koichi Shinhama

Synthetic study on the unique dimeric arylpiperazine: access to the minor contaminant of aripiprazole

The dimeric derivative of aripiprazole was synthesized via the two notable synthetic technologies as a key step: (1) efficient aldehyde bis-arylation by Bi(OTf)(3) and (2) facile Wynberg amination at room temperature. The synthesis has established the structural identity with the minor contaminant sometimes present in Aripiprazole.

A Novel Thiolate Mediated Cyclization to OPC-15161

Abstract An efficient synthetic route to OPC-15161 ( 1 ) was developed via novel pyrazine 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 ) with a lithium arylthiolate. This protocol does not require a free acid intermediate and thus can establish the shortest route to pyrazine dioxide skeleton from tryptophan ester derivatives. In the present transformation, lithium arylthiolates could behave like aluminium arylthiolates, and not like lithium alkylthiolates 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 of a catalytic or stoichiometric promoter which can facilitate several transformations is a key to the success of such reactions. In this paper, we would 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 deprotection-cyclization sequence.