The Synthesis of Vinylogous Amidine Heterocycles

Abstract

We report herein a convenient synthetic methodology for the conversion of meta-dinitro heterocyclic rings to iminoquinones with vinylogous amidine functionality. These structures are found in nature, particularly in marine organisms, and may be important for the pigments and biological activity observed with such marine secondary metabolites. Using benzimidazole and indole ring systems we show the versatility of these vinylogous amidines for organic synthesis, including the following: transamination substitution reactions with virtually any primary amine, regional control of the substitution with substituents between the vinylogous amidine, and hydrolytic properties that can be controlled or optimized based on the properties of the chosen ring system. Taken together, this versatile chemistry and functionalization of organic molecules may be useful in the preparation of a variety of chemical products such as drug pharmacophores or assembling macromolecular structures.

Crystal structure of (E)-2-(tert-butylamino)-4-(tert-butylimino)naphthalen-1(4H)-one

“…These alkaloid secondary metabolites from marine organisms were found to possess cytotoxic antitumor properties. It has been reported that the aminoiminoquinone system may contribute to the cytotoxic activity (LaBarbera & Skibo, 2013). ISSN 2056-9890 Although the 4-imine/2-amine structure was thought to be the most stable, there is evidence for multiple equilibria of these compounds in solution (see reaction scheme).…”

Reactivity of 2,2‐disubstituted quinazolinone towards electrophilic substitution: First in silico design to verify experimental evidence of quinazolinone‐based new organic compounds

“…[10] Functionalization of quinazoline as well as quinazolinone with nitro group is seems to be very promising as it has been observed in the case of natural product for the synthesis of meta-dinitro heterocyclic rings to iminoquinones with vinylogous amidine functionality. [5] Similarly, nitro derivatives of quinazoline 5-substituted-4-hydroxy-8-nitroquinazolines exhibit activity against tumor cell by inhibiting EGFR and ErbB-2 tyrosine kinases. [11,12] Recently, we have reported dinitro and dibromo derivative of 2,2-disubstituted-4-quinazolinone as potent Acetylcholine esterase (AChE) and butyrylcholine esteras (BChE inhibitors) that are found potent than their parent compound.…”

“…[ 1,4a–e ] The chemical functionalization of organic molecules may be useful in the preparation of a variety of chemical products such as drug pharmacophores or assembling macromolecular structures. [ 5 ] Hence, the functionalization of quinazolinone skeleton is important for its further derivatization. Halogenated quinazolinones and quinazolines or their tosylate derivatives via metal‐catalyzed cross‐coupling reactions would afford polycarbo‐ or polyheteroatom‐substituted derivatives of quinazolinone worked as an effective ghrelin receptor and vasopressin V1b receptor antagonists.…”

Macrophilone A: Structure Elucidation, Total Synthesis, and Functional Evaluation of a Biologically Active Iminoquinone from the Marine Hydroid Macrorhynchia philippina

“…Treatment with FeCl 3 /N 2 H 4 resulted in smooth reduction of the dinitroindole 3. 25 Oxidation of this reduced intermediate with potassium nitrosodisulfonate (Fremy’s salt) 26 afforded iminoquinone 4 in 7% yield over two steps. Repeated attempts to improve the yield of this transformation using other oxidants or buffer conditions were not met with success, possibly due to the sensitive nature of the substrate and multiple sites of potential oxidative events.…”