Rok Frlan* Pages 2780 - 2800 ( 21 )
Background: The synthesis of 6-membered pyrrololactams has been studied extensively over the past two decades, in particular because of the diverse biological activities ascribed to many marine-derived alkaloids with pyrrololactam structure. Consequently, many efforts to develop routes of synthesis for the preparation of a large variety of functionalized pyrrololactams have been reported.
Objective: A summary of the progress made over the last 15 years is presented in this review. Eight different isomers of pyrrolopyridinone and the pyrrolopyrazinone bicyclic system are described. Major methods of forming the pyrrololactam system are divided into three general approaches, depending on whether they are based on: (1) derivatization of an existing pyrrole ring followed by cyclization; (2) the formation of a pyrrole framework on the existing 2-piperidinone scaffold; (3) the demethylation of 7-methoxy-azaindole. Special focus is placed on the new methods that have not been covered in other reviews and which mostly describe total synthesis of marine derived secondary metabolites.
Conclusion: A broad range of modern synthetic methods is already available for the preparation of all eight regioisomers of the cyclic 6-membered pyrrolecarboxamide moiety. By presenting this review, we hope that the scientific community will be encouraged in developing novel synthetic routes for the preparation of this resourceful heterocyclic system and to include them as building blocks in the design of novel pharmacologically active compounds.
Pyrrololactam, pyrrolecarboxamide, pyrrolopyridinone, pyrrolopyrazinone, azaindole, cyclization.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Ljubljana