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Quinone methides (QMs) are considered to be highly reactive intermediates because of their aromatization both in chemical and biological systems. Being highly accessible, quinone methides (QMs) have been widely exploited and their concurrent use has been manifested for the synthesis of tertiary and quaternary carbon centers of bioactives, drugs and...
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... the synthesis of p-quinone methides, three approaches are primarily adopted, e.g. phenol-aldehyde condensation, elimination reaction of para-hydroxybenzylalcohol via interim generation of good leaving groups or 1,6-elimination of paracresol having good leaving groups at the benzylic position (Fig. ...
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... 126−128 Despite the fact that these aberrant alkylation processes disrupt normal cellular metabolism and induce cytotoxicity, it has been shown that they can be harnessed for therapeutic purposes. 129,130 For instance, Wijtmans et al. 131 demonstrated that the cytotoxicity of a derivative of aspirin (NO-ASA) is attributed to the generation of QMs in its metabolism rather than the production of nitric oxide or aspirin itself. ...
Stimuli-responsive self-immolative polymers (SIPs) represent a unique class of polymers that can undergo controlled, sequential head-to-tail depolymerization upon specific stimuli. Since their inception, they have evolved over two decades to become one of the most attractive polymer types. With their characteristic feature of “one stimulus, multiple responses”, SIPs inherently possess the ability to serve as chemical amplifiers, which can amplify weak chemical or biological signals. This feature promises higher stimulus sensitivity, greater selectivity for specific microenvironments, and the potential to generate more persistent, extensive, and significant responses while consuming fewer stimuli sources. This Review summarizes the latest research advancements in stimuli-responsive SIPs for drug delivery and molecular imaging over the past five years. Regarding the structure of SIPs, we briefly overview the updates in self-immolation units, end-cap moieties, and sequence of SIPs. In terms of applications, we focus on the possible biological applications of SIPs in drug delivery for disease treatment and potential imaging methods. Finally, we provide a brief perspective of potential future directions for SIPs in these applications.
... Quinones are a class of cyclohexadienedione-containing or cyclohexadiene dimethylene-containing organic compounds that are usually divided into benzoquinones, naphthoquinones, phenanthraquinones, and anthraquinones. 220,221 As shown in Figure 5 and Table S6, quinones and their derivatives provide several promising leading compounds for the development of anti-COVID-19 agents by targeting SARS-CoV-2 3CL pro . It has been reported that tanshinones isolated from Salvia miltiorrhiza are inhibitors of SARS-CoV cysteine proteases (including 3CL pro and PL pro ). ...
The main proteases (Mpro), also termed 3-chymotrypsin-like proteases (3CLpro), are a class of highly conserved cysteine hydrolases in β-coronaviruses. Increasing evidence has demonstrated that 3CLpros play an indispensable role in viral replication and have been recognized as key targets for preventing and treating coronavirus-caused infectious diseases, including COVID-19. This review is focused on the structural features and biological function of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease Mpro (also known as 3CLpro), as well as recent advances in discovering and developing SARS-CoV-2 3CLpro inhibitors. To better understand the characteristics of SARS-CoV-2 3CLpro inhibitors, the inhibition activities, inhibitory mechanisms, and key structural features of various 3CLpro inhibitors (including marketed drugs, peptidomimetic, and non-peptidomimetic synthetic compounds, as well as natural compounds and their derivatives) are summarized comprehensively. Meanwhile, the challenges in this field are highlighted, while future directions for designing and developing efficacious 3CLpro inhibitors as novel anti-coronavirus therapies are also proposed. Collectively, all information and knowledge presented here are very helpful for understanding the structural features and inhibitory mechanisms of SARS-CoV-2 3CLpro inhibitors, which offers new insights or inspiration to medicinal chemists for designing and developing more efficacious 3CLpro inhibitors as novel anti-coronavirus agents.
A DBU‐promoted [3+2] cyclization/retro‐Mannich cascade reaction of N‐aminoisoquinolinium and N‐aminoquinolinium derivatives with para‐quinone methides has been established, employing a C=C double bond cleavage. A broad range of N‐aminoquinolinium salts, N‐aminoisoquinolinium salts, and para‐quinone methides are well tolerated, providing the corresponding rearrangement products. Moreover, scaled‐up reactions and diverse derivatizations of the products were also investigated and discussed.
Hydrogen sulfide (H2S) and associated antioxidant persulfide species respond to oxidative stress. However, tools that reliably generate these species without any potentially toxic byproducs are limited; and even fewer which...
The first chemoselective C4‐benzylation of 5‐aminopyrazoles, utilizing a 3 mol% squaric acid catalyst, is disclosed. In this process, ortho‐quinone methides are efficiently generated from 2‐hydroxybenzyl alcohols in water under mild conditions. This method successfully delivers a wide range of C4‐benzylated 5‐aminopyrazoles, achieving moderate to excellent yields while demonstrating high chemoselectivity, which is further confirmed by mechanistic studies. Notably, the protocol uses water as an eco‐friendly solvent, requires a low organocatalyst loading, and eliminates the need for column chromatography.
We reported a base-promoted cyclization with indene-dienes as two carbon building blocks toward diverse spirocyclic indene scaffolds. Using p-QM in the catalysis system, various hexacyclic spiroindenes bearing benzo pyran motifs...
Quinone methides (QMs) are formed as the intermediates during lignin biosynthesis and chemical transformation; the chemical structure of the resulting lignin can then be significantly modified via the corresponding aromatization....
An efficient transition‐metal‐free multicomponent approach to the regioselective synthesis of highly substituted N‐alkylpyrazoles through 1,6‐addition of pyrazole (in situ generated from α,β‐unsaturated aldehyde and hydrazide) to para‐Quinone Methides has been developed. The N‐alkylpyrazole containing triarylmethanes having several heteroaryl rings (quinoline, pyridine, thiophene) at the central methine carbon atom was developed. This chemical process may be used for large‐scale synthesis and provides a novel way to produce triarylmethanes with diverse functional groups.
Over the years, quinone methides have broadly been applied in synthesis and biological systems for synthesizing heterocyclic compounds and biologically active molecules. In this feature article, we have discussed the novel and uncovered reactivity of o-quinone methides, p-quinone methides, aza-o-quinone methides, and indolyl-2-methides with carbenes generated from α-diazocarbonyl compounds and related compounds. Two in situ-generated transient intermediates undergo cycloannulation reactions, metathesis-type reactions, 1,6-conjugate addition reactions, cyclopropanation reactions, and many other transformations to access nitrogen- and oxygen-containing heterocyclic compounds and beyond. The reactivity of quinone methides and carbenes is observed in various metal catalysts, Brønsted-acids, Lewis acids, phase transfer catalysts, additives, and visible-light-induced transformations.
