C3 Position Of Indoles Research Articles

I. Novel HCV NS5B polymerase inhibitors: Discovery of indole 2-carboxylic acids with C3-heterocycles

SAR development of indole-based palm site inhibitors of HCV NS5B polymerase exemplified by initial indole lead 1 (NS5B IC(50)=0.9 μM, replicon EC(50)>100 μM) is described. Structure-based drug design led to the incorporation of novel heterocyclic moieties at the indole C3-position which formed a bidentate interaction with the protein backbone. SAR development resulted in leads 7q (NS5B IC(50)=0.032 μM, replicon EC(50)=1.4 μM) and 7r (NS5B IC(50)=0.017 μM, replicon EC(50)=0.3 μM) with improved enzyme and replicon activity.

パラジウムを利用したインドール骨格への選択的炭素鎖導入法の開発とその応用

Two new methods for the introduction of a carbon side chain at the C3-position of indoles are presented. The first one is the palladium-catalyzed allylation of 3-bromoindoles with various allyl esters in the presence of hexa-n-butylditin. This is a new type of cross-coupling reaction which does not involve an organometallic reagent as a coupling partner. The second one is the vinylation of bromoindole in the presence of stoichiometric amount of Pd (II) salt. The reaction occurs selectively at the C3-position without affecting the carbon-bromine bond. The first total synthesis of optically acive clavicipitic acid is accomplished by a biomimetic route starting from 4-bromodehydrotryptophan which was prepared in one-step from 4-bromoindole by applying the above selective vinylation.