This review is the first to collate and summarize main data on named and unnamed rearrangement reactions of peroxides. It should be noted, that in the chemistry of peroxides two types of processes ...are considered under the term rearrangements. These are conventional rearrangements occurring with the retention of the molecular weight and transformations of one of the peroxide moieties after O-O-bond cleavage. Detailed information about the Baeyer-Villiger, Criegee, Hock, Kornblum-DeLaMare, Dakin, Elbs, Schenck, Smith, Wieland, and Story reactions is given. Unnamed rearrangements of organic peroxides and related processes are also analyzed. The rearrangements and related processes of important natural and synthetic peroxides are discussed separately.
The biological activity of organic peroxides is usually associated with the antimalarial properties of artemisinin and its derivatives. However, the analysis of published data indicates that organic ...peroxides exhibit a variety of biological activity, which is still being given insufficient attention. In the present review, we deal with natural, semi-synthetic and synthetic peroxides exhibiting anthelmintic, antiprotozoal, fungicidal, antiviral and other activities that have not been described in detail earlier. The review is mainly concerned with the development of methods for the synthesis of biologically active natural peroxides, as well as its isolation from natural sources and the modification of natural peroxides. In addition, much attention is paid to the substantially cheaper biologically active synthetic peroxides. The present review summarizes 217 publications mainly from 2000 onwards.
The present review summarizes publications on the artemisinin peroxide fragment synthesis from 1983 to 2016. The data are classified according to the structures of a precursor used in the key ...peroxidation step of artemisinin peroxide cycle synthesis. The first part of the review comprises the construction of artemisinin peroxide fragment in total syntheses, in which peroxide artemisinin ring resulted from reactions of unsaturated keto derivatives with singlet oxygen or ozone. In the second part, the methods of artemisinin synthesis based on transformations of dihydroartemisinic acid are highlighted.
Although carbon is the central element of organic chemistry, oxygen is the central element of stereoelectronic control in organic chemistry. Generally, a molecule with a C-O bond has both a strong ...donor (a lone pair) and a strong acceptor (
e.g.
, a σ*
C-O
orbital), a combination that provides opportunities to influence chemical transformations at both ends of the electron demand spectrum. Oxygen is a stereoelectronic chameleon that adapts to the varying situations in radical, cationic, anionic, and metal-mediated transformations. Arguably, the most historically important stereoelectronic effect is the anomeric effect (AE),
i.e.
, the axial preference of acceptor groups at the anomeric position of sugars. Although AE is generally attributed to hyperconjugative interactions of σ-acceptors with a lone pair at oxygen (negative hyperconjugation), recent literature reports suggested alternative explanations. In this context, it is timely to evaluate the fundamental connections between the AE and a broad variety of O-functional groups. Such connections illustrate the general role of hyperconjugation with oxygen lone pairs in reactivity. Lessons from the AE can be used as the conceptual framework for organizing disjointed observations into a logical body of knowledge. In contrast, neglect of hyperconjugation can be deeply misleading as it removes the stereoelectronic cornerstone on which, as we show in this review, the chemistry of organic oxygen functionalities is largely based. As negative hyperconjugation releases the "underutilized" stereoelectronic power of unshared electrons (the lone pairs) for the stabilization of a developing positive charge, the role of orbital interactions increases when the electronic demand is high and molecules distort from their equilibrium geometries. From this perspective, hyperconjugative anomeric interactions play a unique role in guiding reaction design. In this manuscript, we discuss the reactivity of organic O-functionalities, outline variations in the possible hyperconjugative patterns, and showcase the vast implications of AE for the structure and reactivity. On our journey through a variety of O-containing organic functional groups, from textbook to exotic, we will illustrate how this knowledge can predict chemical reactivity and unlock new useful synthetic transformations.
The chameleonic properties of oxygen accounts for the diverse reactivity of O-functionalities and their profound role in organic synthesis.
A synthesis of bridged 1,2,4-trioxolanes (bridged ozonides) from 1,5-diketones and hydrogen peroxide catalyzed by SnCl4 was developed. It was shown that the ratio of target ozonides can be affected ...by the application of SnCl4 as a catalyst and varying the solvent. A wide range of bridged 1,2,4-trioxolanes (ozonides) was obtained in yields from 50 to 84%. The ozonide cycle was moderately resistant to the reduction of the ester group near the peroxide cycle to alcohol with LiAlH4. The bridged ozonides were evaluated for their antischistosomal activity. These ozonides exhibited a very high activity against newly transformed schistosomula and adult Schistosoma mansoni.
A photocatalytic three-component sulfonyl peroxidation of alkenes with N-sulfonyl ketimines and tert-butyl hydroperoxide is reported. The reaction takes place via the photoinduced EnT process, which ...allows the efficient synthesis of a variety of β-peroxyl sulfones under mild reaction conditions in the absence of a transition metal catalyst. The downstream derivatizations of the peroxides were also performed. Furthermore, the utility of this protocol was manifested by the synthesis of 11β-HSD1 inhibitor and the antiprostate cancer drug bicalutamide.
The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) cause life‐threatening diseases in millions of people worldwide, in particular, in patients with cancer, and there is an ...urgent need for antiviral agents against this infection. While in vitro activities of artemisinins against SARS‐CoV‐2 and cancer have recently been demonstrated, no study of artemisinin and/or synthetic peroxide‐based hybrid compounds active against both cancer and SARS‐CoV‐2 has been reported yet. However, the hybrid drug's properties (e. g., activity and/or selectivity) can be improved compared to its parent compounds and effective new agents can be obtained by modification/hybridization of existing drugs or bioactive natural products. In this study, a series of new artesunic acid and synthetic peroxide based new hybrids were synthesized and analyzed in vitro for the first time for their inhibitory activity against SARS‐CoV‐2 and leukemia cell lines. Several artesunic acid‐derived hybrids exerted a similar or stronger potency against K562 leukemia cells (81–83 % inhibition values) than the reference drug doxorubicin (78 % inhibition value) and they were also more efficient than their parent compounds artesunic acid (49.2 % inhibition value) and quinoline derivative (5.5 % inhibition value). Interestingly, the same artesunic acid‐quinoline hybrids also show inhibitory activity against SARS‐CoV‐2 in vitro (EC50 13–19 μm) and no cytotoxic effects on Vero E6 cells (CC50 up to 110 μM). These results provide a valuable basis for design of further artemisinin‐derived hybrids to treat both cancer and SARS‐CoV‐2 infections.
Hybrid power: New artemisinin‐ and synthetic peroxide‐based hybrids, highly active in vitro against leukemia cell lines and SARS‐CoV‐2, were synthesized. Remarkably, the most active anti‐cancer hybrid compounds are also the most potent and selective against SARS‐CoV‐2.
Although antischistosomal properties of peroxides were studied in recent years, systematic structure–activity relationships have not been conducted. We evaluated the antischistosomal potential of 64 ...peroxides belonging to bridged 1,2,4,5-tetraoxanes, alphaperoxides, and tricyclic monoperoxides. Thirty-nine compounds presented IC50 values <15 μM on newly transformed schistosomula. Active drugs featured phenyl-, adamantane-, or alkyl residues at the methylene bridge. Lower susceptibility was documented on adult schistosomes, with most hit compounds being tricyclic monoperoxides (IC50: 7.7–13.4 μM). A bridged 1,2,4,5-tetraoxane characterized by an adamantane residue showed the highest activity (IC50: 0.3 μM) on adult Schistosoma mansoni. Studies with hemin and heme supplemented medium indicated that antischistosomal activation of peroxides is not necessarily triggered by iron porphyrins. Two compounds (tricyclic monoperoxide; bridged 1,2,4,5-tetraoxane) revealed high worm burden reductions in the chronic (WBR: 75.4–82.8%) but only moderate activity in the juvenile (WBR: 18.9–43.1%) S. mansoni mouse model. Our results might serve as starting point for the preparation and evaluation of related derivatives.
In recent years, the number of pollinators in the world has significantly decreased. A possible reason for this is the toxic effects of agrochemicals reducing the immunity of insects that leads to ...their increased susceptibility to pathogens.
is a dangerous entomopathogenic fungus, afflicting both honeybees and bumblebees. We investigated fungicide activity of cyclic synthetic peroxides against
isolated from
L. The peroxides exhibited high mycelium growth inhibition of
up to 94-100% at concentration 30 mg/L. EC
values were determined for the most active peroxides. Two peroxides showed higher antifungal activity against
than the commercial fungicide Triadimefon. The studied peroxides did not reduce the ability of bumblebees to fly and did not lead to the death of bumblebees. A new field of application for peroxides was disclosed.
A selective reaction of bridged ozonides with Fe(II) salts proceeds through the sequence of O−O, C−C scissions and halogenation to form α‐halogen substituted δ‐ketoesters and δ‐diketones in 15–72% ...yields. The overall sequence shows how a temporary installation of a peroxide functionality can be used to replace the acyl group within an acetoacetic ester unit with a halogen.
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