Chemistry of Pyrazino[2,1-b]quinazoline-3,6-diones

Abstract

The pyrazino[2,1-b]quinazoline-3,6-dione system is the key structural fragment of a group of alkaloids. The synthesis of derivatives of this system has been accomplished by means of three kinds of methods, starting from 4(3H)-quinazolinones, 2,5-piperazinediones or open-chain tripeptides, where anthranilic acid can be at the C-terminal, the N-terminal or the intermediate position of the tripeptide. Regarding its reactivity, much work has been developed to show that the system behaves as a glycine template. Thus, its C-1 position can be deprotonated by strong bases, and the anion thus generated undergoes stereoselective alkylations, acylations and Michael reactions. Hypervalent iodine reagents commonly employed for the α-functionalization of ketones also react at C-1, leading to electrophilic species that can be arylated and therefore used as precursors to polycyclic derivatives. Oxidation and Mannich reactions also occur at the C-1 position and lead to precursors of tertiary iminium cations. Some rearrangement reactions have been described, including a pyrazine-pyridine transformation and a transannular rearrangement that has ben proposed to explain some reactivity results. The aromatic ring of pyrazino[2,1-b]quinazoline-3,6-diones can be easily hydrogenated to give tetrahydro derivatives.

Enzymatic Processing of Fumiquinazoline F: A Tandem Oxidative-Acylation Strategy for the Generation of Multicyclic Scaffolds in Fungal Indole Alkaloid Biosynthesis

“…One class of fungal natural products are the quinazoline alkaloids (2, 3), of which a subclass is the fumiquinazolines (FQs) with a pyrazino[2,1- b ]quinazoline-3,6-dione core scaffold derived from condensation of anthranilic acid (Ant) with two additional amino acids (Figure S1) (4). …”

Microwave-Promoted Total Synthesis of Puniceloid D for Modulating the Liver X Receptor

“…Derivatives of this system have been synthesized using three distinct methods: the cyclization of 4(3 H )-quinazolinones (a), the cyclocondensation of 2,5-piperazinediones and anthranilic acid derivatives (b), and the use of open-chain tripeptides, with anthranilic acid positioned at the C-terminal (c1), N-terminal (c2), or as the intermediate residue (c3) [ 23 ] ( Figure 3 ).…”