A facile synthesis of quinazolino[1,4]benzodiazepine natural alkaloids

Abstract

<p>A facile and short synthesis of a series of quinazolino[[3,2-a][1,4]benzodiazepine scaffold found in several biologically active naturally occurring alkaloids, including asperlicin C, circumdatin H and benzomalvin A is reported. Coupling of [1,4]benzodiazepine with 2- nitrobenzoyl chlorides, followed by a reductive N-heterocyclization afforded the quinazolino[[3,2-a][1,4]benzodiazepine ring system. Furthermore Lewis acid (MgCl2, ZnCl2) mediated cyclodehydration of a linear tripeptide comprised of three amino acid units provided the tricyclic quinazolino[3,2-d][1,4]benzodiazepine ring system found in few biologically active natural alkaloids. This methodology, implemented with a tripeptide encompassing the sequence of anthranilic-anthranilic-tryptophan methyl ester, furnish the first total synthesis of asperlicin D.</p><p>A facile and short synthesis of a series of quinazolino[[3,2-a][1,4]benzodiazepine scaffold found in several biologically active naturally occurring alkaloids, including asperlicin C, circumdatin H and benzomalvin A is reported. Coupling of [1,4]benzodiazepine with 2- nitrobenzoyl chlorides, followed by a reductive N-heterocyclization afforded the quinazolino[[3,2-a][1,4]benzodiazepine ring system. Furthermore Lewis acid (MgCl2, ZnCl2) mediated cyclodehydration of a linear tripeptide comprised of three amino acid units provided the tricyclic quinazolino[3,2-d][1,4]benzodiazepine ring system found in few biologically active natural alkaloids. This methodology, implemented with a tripeptide encompassing the sequence of anthranilic-anthranilic-tryptophan methyl ester, furnish the first total synthesis of asperlicin D.</p>