Natural products play a key role in the history of human drug discovery, and especially for the anticancer agents. Copper(I)-catalyzed alkyne-azide 3+2 cycloaddition (CuAAC) reaction is perhaps the ...most powerful method for the efficient modification of complex natural products, enabling the direct incorporation of various functional groups accompanied by the formation of the multifunctional 1,2,3-triazole motif, which could not only serve as an basic and hydrophilic connecting group but also as a bioisosteres of 5- or 6-membered heterocycles or an amide group, thus facilitating the improvement of anticancer activities and/or drug-like properties. This contribution extensively summarizes the state-of-the-art application of 1,2,3-triazole in the modification of natural products for anticancer activity. The aim is to gain a deep understanding of the fruitful achievements as well as limitations of CuAAC click chemistry in natural product modification for anticancer activity, and provide perspectives and directions regarding future studies in natural product medicinal chemistry.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A successful DNA‐encoded library (DEL) will consist of diverse skeletons and cover chemical space as comprehensive as possible to fully realize its potential in drug discovery and chemical biology. ...However, the lack of versatile on‐DNA arylation methods for phenols that are less nucleophilic and reactive poses a great hurdle for DEL to include diaryl ether, a privileged chemotype in pharmaceuticals and natural products. This work describes the use of “substrate activation” approach to address the arylation of DNA‐conjugated phenols. Diaryliodonium salt, a highly electrophilic and reactive arylation reagent, is employed as Ar+ sources to ensure highly selective on‐DNA arylation of phenols and oximes with both high yields and DNA fidelity. Notably, the new on‐DNA arylation reaction can be applied to the late‐stage modification of peptides containing tyrosine side‐chain and to synthesize DNA‐tagged analogues of existing drug molecules such as sorafenib, a known pan‐kinase inhibitor. The new on‐DNA diaryliodonium salts chemistry affords a greater flexibility in DEL design and synthesis.
The first on‐DNA diaryliodonium slats (DAIs) chemistry is developed by substrate activation strategy. The selective on‐DNA arylation methods of phenols and oximes with both high yield and DNA fidelity are developed. The applicable potentiality of these reactions is demonstrated by pilot on‐DNA synthesis of analogs of clinically used drug sorafenib and late‐stage modification of peptides.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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•The main organoselenium species have different structural properties.•We focus on selenium containing heterocycles and natural products.•We provide information to guide the rational ...design of selenium-containing drugs.
The diverse pharmacological activities of organoselenium compounds are closely correlated to their ability to scavenge and induce reactive oxygen species (ROS), their intrinsic oxidative properties, and their Se(0) release property. The incorporation of selenium into small molecules, and particularly into heterocycles and natural products, has shown great potential in altering the potency and selectivity of these molecules. Therefore, selenium will play an important role in drug discovery in the near future. We summarize how different organoselenium species affect cellular oxidative stress levels, and try to correlate the structural properties of selenium-containing heterocycles and natural product derivatives to their biological activities and therapeutic applications. We also provide some information to guide the rational design of selenium-containing drugs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Hartmann-Tran Profile and its asymptotic limits are studied by analyzing the P 32e line from 12C16O2 band.•The equivalence of asymptotic limits of HTP to their ordinary counterparts are ...verified.•The fitted partial-correlation coefficient is close to zero with relatively large uncertainty, making the line-narrowing coefficients less reliable.
In this paper, the Hartmann-Tran profile (HTP) and its asymptotic limits are employed to analyze the experimentally-measured absorption spectra of CO2 gas. The fitted results by multi-spectrum fitting are compared to those from the ordinary line-shape models. The equivalence and computational efficiency of the asymptotic limits of HTP to their ordinary counterparts are studied. The research shows that the parameters of line position ω0, intensity S, pressure broadening coefficient Γ0/p and shifting coefficient Δ0/p by HTP agree well with those from the speed-dependent hard-collision line-shapes. In comparison, the poorly-determined partial-correlation parameter η makes the fitted line-narrowing parameters less reliable.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Selenium (Se) is an emerging versatile player in medicinal chemistry. The incorporation of Se into small molecules and natural products could have multiple benefits. However, the lack of efficient ...methods for the synthesis of Se‐containing chemical library has greatly hindered the development of seleno‐medicinal chemistry. With the aim to address this issue, we proposed the development of “clickable selenylation” reactions, which can be used in the synthesis of Se‐containing in situ library and DNA‐encoded library (SeDEL), thereby quickly producing ultra‐large collections of Se‐containing compounds and boosting the development of seleno‐medicinal chemistry. This research paradigm can be concluded as “clickable selenylation chemistry development→in situ library construction/SeDEL synthesis→phenotype‐ or target‐based screening→seleno‐hit compound”.
Selenium is an emerging versatile player in medicinal chemistry, however, the research on org‐Se therapeutic agents is still in its infancy due to lack of efficient selenylation chemistry. To circumvent the lack of efficient methods for the synthesis of org‐Se library, the concept of clickable selenylation was proposed for their practical application in parallel library and DNA‐encoded library synthesis.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Click chemistry is a powerful molecular assembly strategy for rapid functional discovery. The development of click reactions with new connecting linkage is of great importance for expanding the click ...chemistry toolbox. We report the first selenium‐nitrogen exchange (SeNEx) click reaction between benzoselenazolones and terminal alkynes (Se−N to Se−C), which is inspired by the biochemical SeNEx between Ebselen and cysteine (Cys) residue (Se−N to Se−S). The formed selenoalkyne connection is readily elaborated, thus endowing this chemistry with multidimensional molecular diversity. Besides, this reaction is modular, predictable, and high‐yielding, features fast kinetics (k2≥14.43 M−1 s−1), excellent functional group compatibility, and works well at miniaturization (nanomole‐scale), opening up many interesting opportunities for organo‐Se synthesis and bioconjugation, as exemplified by sequential click chemistry (coupled with ruthenium‐catalyzed azide‐alkyne cycloaddition (RuAAC) and sulfur‐fluoride exchange (SuFEx)), selenomacrocycle synthesis, nanomole‐scale synthesis of Se‐containing natural product library and DNA‐encoded library (DEL), late‐stage peptide modification and ligation, and multiple functionalization of proteins. These results indicated that SeNEx is a useful strategy for new click chemistry developments, and the established SeNEx chemistry will serve as a transformative platform in multidisciplinary fields such as synthetic chemistry, material science, chemical biology, medical chemistry, and drug discovery.
The concept of selenium‐nitrogen exchange (SeNEx) click chemistry is put forward based on the excellent performance of the reaction between benzoselenazolones and terminal alkynes. The reaction exhibits modularity, robustness, mild reaction conditions, and fast kinetics (k2≥14.43 M−1 s−1), and its broad applicability is demonstrated with examples of on‐plate nanomole‐scale parallel synthesis, DNA‐encoded library synthesis, and peptide and protein modification.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Click chemistry is a concept wherein modular synthesis is used for rapid functional discovery. To this end, continuous discovery of clickable chemical transformations is the pillar to support the ...development of this field. This report details the development of a clickable C3‐H selenylation of indole that is suitable for on‐plate parallel and DNA‐encoded library (SeDEL) synthesis via bioinspired LUMO activation strategy. This reaction is modular, robust and highly site‐selective, and it features a simple and mild reaction system (catalyzed by nonmetallic B(C6F5)3 at room temperature), high yields and excellent functional group compatibility. Using this method, a library of 1350 indole‐selenides was parallel synthesized in an efficient and practical manner, enabling the rapid identification of 3 ai as a promising compound with nanomolar antiproliferative activity in cancer cells via in situ phenotypic screening. These results indicate the great potential of this new clickable selenylation reaction in high‐throughput medicinal chemistry and chemical biology.
A bioinspired clickable selenylation reaction of indole has been developed by using benzoselenazole as selenylation reagent under nonmetallic B(C6F5)3 catalysis. The practical application of the reaction has been well demonstrated in on‐DNA and on‐microplate parallel synthesis of indole‐selenides.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Selenium–nitrogen exchange (SeNEx) chemistry creates seleno‐connecting linkage to efficiently explore the organo‐Se chemical world. In their Research Article (e202318534), Wei Hou, Hongtao Xu et al. ...put forward the concept of SeNEx chemistry based on the excellent performance of the reaction between benzoselenazolones and terminal alkynes. This reaction exhibits modularity, robustness, mild reaction conditions, and fast kinetics, and can be used in nanomole‐scale parallel synthesis, DNA‐encoded library synthesis, and peptide and protein bioconjugation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Selenium–nitrogen exchange (SeNEx) chemistry creates seleno‐connecting linkage to efficiently explore the organo‐Se chemical world. In their Research Article (e202318534), Wei Hou, Hongtao Xu et al. ...put forward the concept of SeNEx chemistry based on the excellent performance of the reaction between benzoselenazolones and terminal alkynes. This reaction exhibits modularity, robustness, mild reaction conditions, and fast kinetics, and can be used in nanomole‐scale parallel synthesis, DNA‐encoded library synthesis, and peptide and protein bioconjugation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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