Studies Towards Bioactive Imidazoles

Abstract

The work presented in this thesis focuses on the development of an enantioselective and practical route form the total synthesis of villagorgin via haplosleridamine imidazole alkaloid containing β- carboline moiety by employing the well-known Pictet-Spengler and Fischer indole reactions. We approached two different ways inorder to synthesize these molecules Our first approach focused on using a Dieckmann condensation, requiring the preparation of the corresponding diester. Initial attempts to prepare this substrate directly from histidine were unsuccessful, however after conversion to the N-benzzylamine and reductive amination with ester provided the key diester compound. Unfortunately, attempts to effect the Dieckmann reaction were not successful. In addition we became concerned about the possibility of racemization under the basic condition In the second approach - Ring closing Metathesis : the key intermediate piperidinone was assembled from a protected histidine , allyation and Grignard chemistry. RCM reaction developed in our lab gave the key heterocycle though in a moderate yield (unoptimized). Reduction followed by the installation of the indole moiety, which would complete the core framework. Deprotection would the give the halopscleridamine and a subsequent pictet-Spengler reaction would then give villagorgin A.