scholarly journals Click Chemistry in Natural Product Modification

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiang Zhang ◽  
Shuning Zhang ◽  
Songfeng Zhao ◽  
Xuan Wang ◽  
Bo Liu ◽  
...  

Click chemistry is perhaps the most powerful synthetic toolbox that can efficiently access the molecular diversity and unique functions of complex natural products up to now. It enables the ready synthesis of diverse sets of natural product derivatives either for the optimization of their drawbacks or for the construction of natural product-like drug screening libraries. This paper showcases the state-of-the-art development of click chemistry in natural product modification and summarizes the pharmacological activities of the active derivatives as well as the mechanism of action. The aim of this paper is to gain a deep understanding of the fruitful achievements and to provide perspectives, trends, and directions regarding further research in natural product medicinal chemistry.

2018 ◽  
Author(s):  
Jonathan J. Mills ◽  
Kaylib R. Robinson ◽  
Troy E. Zehnder ◽  
Joshua G. Pierce

The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogs to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.


2018 ◽  
Vol 54 (86) ◽  
pp. 12234-12237 ◽  
Author(s):  
Edward S. Hems ◽  
Ben A. Wagstaff ◽  
Gerhard Saalbach ◽  
Robert A. Field

In the context of discovering and quantifying terminal alkyne-based natural products, here we report the combination of CuAAC click chemistry with LC-MS for the detection of polyether toxins (prymnesins) associated with harmful algal blooms.


2018 ◽  
Author(s):  
Jonathan J. Mills ◽  
Kaylib R. Robinson ◽  
Troy E. Zehnder ◽  
Joshua G. Pierce

The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogs to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.


2015 ◽  
Vol 32 (4) ◽  
pp. 605-632 ◽  
Author(s):  
Michail Tsakos ◽  
Eva S. Schaffert ◽  
Lise L. Clement ◽  
Nikolaj L. Villadsen ◽  
Thomas B. Poulsen

In this review we investigate the use of complex ester fragment couplings within natural product total syntheses. Using examples from the literature up to 2014 we illustrate the state-of-the-art as well as the challenges within this area of organic synthesis.


2019 ◽  
Vol 20 (4) ◽  
pp. 293-301 ◽  
Author(s):  
Baoyu Yang ◽  
Jing Mao ◽  
Bing Gao ◽  
Xiuli Lu

Background:Computer-assisted drug virtual screening models the process of drug screening through computer simulation technology, by docking small molecules in some of the databases to a certain protein target. There are many kinds of small molecules databases available for drug screening, including natural product databases.Methods:Plants have been used as a source of medication for millennia. About 80% of drugs were either natural products or related analogues by 1990, and many natural products are biologically active and have favorable absorption, distribution, metabolization, excretion, and toxicology.Results:In this paper, we review the natural product databases’ contributions to drug discovery based on virtual screening, focusing particularly on the introductions of plant natural products, microorganism natural product, Traditional Chinese medicine databases, as well as natural product toxicity prediction databases.Conclusion:We highlight the applications of these databases in many fields of virtual screening, and attempt to forecast the importance of the natural product database in next-generation drug discovery.


2018 ◽  
Author(s):  
William A. Shirley ◽  
Brian P. Kelley ◽  
Yohann Potier ◽  
John H. Koschwanez ◽  
Robert Bruccoleri ◽  
...  

This pre-print explores ensemble modeling of natural product targets to match chemical structures to precursors found in large open-source gene cluster repository antiSMASH. Commentary on method, effectiveness, and limitations are enclosed. All structures are public domain molecules and have been reviewed for release.


2020 ◽  
Vol 26 ◽  
Author(s):  
Shaik Ibrahim Khalivulla ◽  
Arifullah Mohammed ◽  
Kokkanti Mallikarjuna

Background: Diabetes is a chronic disease affecting a large population worldwide and stands as one of the major global health challenges to be tackled. According to World Health Organization, about 400 million are having diabetes worldwide and it is the seventh leading cause of deaths in 2016. Plant based natural products had been in use from ancient time as ethnomedicine for the treatment of several diseases including diabetes. As a result of that, there are several reports on plant based natural products displaying antidiabetic activity. In the current review, such antidiabetic potential compounds reported from all plant sources along with their chemical structures are collected, presented and discussed. This kind of reports are essential to pool the available information to one source followed by statistical analysis and screening to check the efficacy of all known compounds in a comparative sense. This kind of analysis can give rise to few numbers of potential compounds from hundreds, whom can further be screened through in vitro and in vivo studies, and human trails leading to the drug development. Methods: Phytochemicals along with their potential antidiabetic property were classified according to their basic chemical skeleton. The chemical structures of all the compounds with antidiabetic activities were elucidated in the present review. In addition to this, the distribution and their other remarkable pharmacological activities of each species is also included. Results: The scrutiny of literature led to identification of 44 plants with antidiabetic compounds (70) and other pharmacological activities. For the sake of information, the distribution of each species in the world is given. Many plant derivatives may exert antidiabetic properties by improving or mimicking the insulin production or action. Different classes of compounds including sulfur compounds (1-4), alkaloids (5-11), phenolic compounds (12-17), tannins (18-23), phenylpropanoids (24-27), xanthanoids (28-31), amino acid (32), stilbenoid (33), benzofuran (34), coumarin (35), flavonoids (36-49) and terpenoids (50-70) were found to be active potential compounds for antidiabetic activity. Of the 70 listed compounds, majorly 17 compounds are from triterpenoids, 13 flavonoids and 7 are from alkaloids. Among all the 44 plant species, maximum number (7) of compounds are reported from Lagerstroemia speciosa followed by Momordica charantia (6) and S. oblonga with 5 compounds. Conclusion: This is the first paper to summarize the established chemical structures of phytochemicals that have been successfully screened for antidiabetic potential and their mechanisms of inhibition. The reported compounds could be considered as potential lead molecules for the treatment of type-2 diabetes. Further, molecular and clinical trials are required to select and establish the therapeutic drug candidates.


2020 ◽  
Vol 17 (2) ◽  
pp. 82-90 ◽  
Author(s):  
Ghodsi Mohammadi Ziarani ◽  
Fatemeh Mohajer ◽  
Zohreh kheilkordi

Background: Natural products have been received attention due to their importance in human life as those are biologically active. In this review, there are some reports through different methods related to the synthesis of the indolizidine 195B which was extracted from poisonous frog; however, due to respect nature, the synthesis of natural compounds such as indolizidine has been attracted much attention among scientists and researchers. Objective: This review discloses the procedures and methods to provide indolizidine 195B from 1989 to 2018 due to their importance as a natural product. Conclusion: There are several methods to give rise to the indolizidine 195B as a natural product that is highly active from the biological perspective in pharmaceutical chemistry. In summary, many protocols for the preparations of indolizidine 195B from various substrates, several reagents, and conditions have been reported from different aromatic and aliphatic.


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