Synthesis of new representatives of 11,12-dihydro-5 H -5,11-epoxybenzo[7,8]oxocino[4,3- b ]pyridines – structural analogues of integrastatins A, B

The Claisen–Schmidt condensation reaction of 3,5-diacetyl-2,6-dimethylpyridine with salicylic aldehyde in the presence of an acid unexpectedly afforded 1-((5 S ,11 S )-2,5-dimethyl-11,12-dihydro-5 H -5,11-epoxybenzo[7,8]oxocino[4,3- b ]pyridin-3-yl)ethan-1-one as the product of intramolecular cyclization instead of α,β-unsaturated ketones (mono- or bis-azachalcones). The obtained 1-((5 S ,11 S )-2,5-dimethyl-11,12-dihydro-5 H -5,11-epoxybenzo[7,8]oxocino[4,3- b ]pyridin-3-yl)ethan-1-one is a close nitrogen-containing structural analogue of natural inhibitors of HIV-1 integrase, namely integrastatins A and B , epicoccolide A and epicocconigrone A , containing a tetracyclic epoxybenzooxocine fragment. Substrate scope and mechanistic insights into the cyclization reaction were investigated. A possibility of selective oxidation of the methylene group of the oxocine ring with selenous acid to the carbonyl group was shown to prove structural similarity of the synthesized pyridine-containing analogs with the integrastatin scaffold.