The recent impact of solid-phase synthesis on medicinally relevant benzoannelated nitrogen heterocycles

Abstract

Benzoannelated heterocycles such as benzodiazepines and indoles can be prepared efficiently through cyclization on solid supports, although no single approach is currently universal for the preparation of all benzoannelated N-heterocycle chemistries. In this review, a number of synthetic strategies for the generation of benzoannelated nitrogen heterocycles using resin-bound substrates have been described. Classical heterocycle forming reactions such as the Fischer indole, the Bischler–Napieralski tetrahydroisoquinoline, the Pictet–Spengler tetrahydro-β-carboline, the Tsuge, the Nenitzescu and the Richter cinnoline reaction are presented. In addition, the Heck, Sonogashira, Wittig, Diels–Alder, and olefin metathesis reactions have been also used. Multicomponent reactions such as the Grieco three-component assembly have been exploited for the synthesis of heterocycles. Cyclative cleavage from the solid support is particularly suitable for the synthesis of heterocycles while particular emphasis has been focused on the synthesis of libraries and the use of combinatorial chemistry techniques. In addition, the most relevant pharmacological properties of benzoannelated nitrogen heterocycles are included.