2,5-Diketopiperazine Catalysts as Activators of Dioxygen in Oxidative Processes

Abstract

The ability of natural and non-natural dipeptides to act as activators of dioxygen in the absence of metallic cocatalysts is reported here. Proline-derived 2,5diketopiperazines were found active as catalytic mediators for various chemoselective aerobic oxidation processes including the oxidation of sulfides to sulfoxides, the epoxidation of alkenes, and the oxidative coupling of phenols. Mechanistic studies and intercepted intermediates evidence the existence of catalytically active hydroperoxide species that work in unison in a catalytic cycle that resembles the mechanism of flavincontaining monooxygenases.

A Review of the Synthetic Strategies toward Dihydropyrrolo[1,2-a]Pyrazinones

“…These compounds 38 could be oxygenated with molecular oxygen to a hydroperoxide and could be reduced in situ with dibutyl sulfide ((n-Bu)2S) or tripheny phosphine (PPh3), affording the hydroxy product 39 in high yield [62] (Scheme 10). Re cently, it was found that these diketopiperazines 38 could function as catalysts in oxygen ation reactions [65], and the oxygenation of compound 38 in the presence of guanidine has also been mentioned as acting in the biogenesis of 2-aminoimidazolidinone metabo lites from sponges [61]. Amides 37, resulting from the condensation of 2-trichloroacetylpyrrole (or pyrrole-2carboxylic acid and amidation reagents) and different amino esters derived from natural amino acids (shown here for proline), were cyclized with sodium hydride in THF to the diketopiperazine derivatives 38 in high yield.…”

“…These compounds 38 could be oxygenated with molecular oxygen to a hydroperoxide and could be reduced in situ with dibutyl sulfide ((n-Bu) 2 S) or triphenyl phosphine (PPh 3 ), affording the hydroxy product 39 in high yield [62] (Scheme 10). Recently, it was found that these diketopiperazines 38 could function as catalysts in oxygenation reactions [65], and the oxygenation of compound 38 in the presence of guanidine has also been mentioned as acting in the biogenesis of 2-aminoimidazolidinone metabolites from sponges [61]. Pyrrole-2-carboxylic acid, carbonyl compounds, isocyanides and amino esters un dergo the four-component Ugi reaction to afford the adducts, which cyclized spontane ously at room temperature in methanol and triethylamine (Et3N) to afford a library o polysubstituted pyrrole diketopyrazines 40 [66] (Scheme 11).…”

“…An extensive discussion o pyrrolo-fused diketopiperazines is out of the scope of this review. Instead, we give a few additional key references [57,65,[67][68][69][70].…”

“…An extensive discussion of pyrrolo-fused diketopiperazines is out of the scope of this review. Instead, we give a few additional key references [57,65,[67][68][69][70]. Pyrrole-2-carboxylic acid, carbonyl compounds, isocyanides and amino esters un dergo the four-component Ugi reaction to afford the adducts, which cyclized spontane ously at room temperature in methanol and triethylamine (Et3N) to afford a library o polysubstituted pyrrole diketopyrazines 40 [66] (Scheme 11).…”

Cyclic Dipeptides Formation From Linear Dipeptides Under Potentially Prebiotic Earth Conditions

“…The prebiotic peptide synthesis and the origin of bio-chirality remain an abstruse problem. Cyclic dipeptides [2, 5-diketopiperazines, (DKPs)] have been found to have peptides elongating and chiral catalysis properties ( Mauger, 1968 ; Bycroft, 1969 ; Poullennec et al, 2002 ; Huber et al, 2003 ; Borthwick, 2012 ; Danger et al, 2012 ; Petsi and Zografos, 2020 ). The DKPs could act as activated intermediates in the formation of peptides as was suggested by Yamagata et al and Imai et al ( Nagayama et al, 1990 ; Takaoka et al, 1991 ; Imai et al, 1999 ).…”