Late stage functionalization of cyclic terpenoids by atom transfer radical addition. A convenient route towards nitrogen heterocycles

Abstract

Terpens are a class of widely spread natural compounds with a broad range of biological properties, showing ‘drug-like’ chemical properties, including lipophilicity, interesting molecular geometry, alkylating center reactivity etc [1]. Nevertheless, nitrogen-containing terpens, which can show diverse functionality and biological activity in living cells, are rare in natural sources. We present in this communication the atom transfer radical additions performed on relevant terpene derivatives of labdane and drimane framework, compounds 1-3, and resulting in a series of azido-compounds. Carboazidation of correspomding terpenic olefins was carried out with ethyliodoacetate under specific conditions using di-tert-butyl hyponitrite (DTBHN) as free radical initiator and phenylsolfonylazide as the azide radical source [2]. The addition products formed with excellent yields. Subsequent modifications to the azide group, such as catalytic hydrogenation, led to spontaneous lactamization, resulting in the formation of γ-lactam products. Our investigations revealed that stereochemical constraints play an important role in these transformations, both at addition and reduction steps. Following assessment of the interactions of these compounds with biomolecular targets is under way.