A first biosynthetic proposal for the in vivo formation of naturally occurring diazepam-like 1,4-benzodiazepines

Abstract

A first rational concept for the in vivo formation of naturally occurring diazepam-type 1,4-benzodiazepines is suggested--by oxidative carbon-carbon bond cleavage of the known quinoline alkaloid viridicatin, a fungal metabolite from Penicillium species, replacement of the resulting N-oxaloyl substituent by a glycinoyl residue, and subsequent ring closure under Schiff base formation. In principle, all the proposed individual reaction steps as such are known from the literature: they have either been proven to occur in vivo, or they have been performed chemically. According to this concept, diazepam-type benzodiazepines would not only represent the joint result of both industrial developments and evolutionary processes in nature, but would even arise from identical precursors--ortho-aminobenzophenone and glycine! Alternatively, according to a slightly modified (more "economical") biogenetic concept, the oxaloyl residue would not be substituted, but rather converted into the glycinoyl part. This hypothetic biosynthesis of naturally occurring 1,4-benzodiazepines might proceed in part in microorganisms (e.g. in fungi) and in part in higher organisms (e.g. in plants).