Abstract:Triazolyl phenylalanine and tyrosine-aryl C-glycoside hybrids were readily synthesized via microwave-assisted Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition in high yields. Successive enzymatic assay identified the synthesized glycoconjugates as novel PTP1B inhibitors with low micromole-ranged inhibitory activity and at least several-fold selectivity over other homologous PTPs tested. In addition, the benzyl groups on glucosyl moiety were found crucial toward PTP1B inhibition. Reagents and conditions: … Show more
“…The successive bioassay for PTP1B activity for these glyconconjugates suggests that molecules containing carboxylic acid and benzyl moieties were the most potential PTP1B inhibitors (IC 50 = 5.6 μM for 580 and IC 50 = 5.5 μM for 581). 584 A class of mono-and bisphenylalaninyl and -tyrosinyl glucosides were recognized as PTP1B inhibitors by the Chen group. 585 Glucosyl scaffolds incorporated with one or two phenylalanine or tyrosine substituents on the 2,3-, 2,6-, 3,4-, 4,6-, and 6-positions were synthesized in excellent yields under MWassisted click chemistry.…”
Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC), popularly known as the "click reaction", serves as the most potent and highly dependable tool for facile construction of simple to complex architectures at the molecular level. Click-knitted threads of two exclusively different molecular entities have created some really interesting structures for more than 15 years with a broad spectrum of applicability, including in the fascinating fields of synthetic chemistry, medicinal science, biochemistry, pharmacology, material science, and catalysis. The unique properties of the carbohydrate moiety and the advantages of highly chemo- and regioselective click chemistry, such as mild reaction conditions, efficient performance with a wide range of solvents, and compatibility with different functionalities, together produce miraculous neoglycoconjugates and neoglycopolymers with various synthetic, biological, and pharmaceutical applications. In this review we highlight the successful advancement of Cu(I)-catalyzed click chemistry in glycoscience and its applications as well as future scope in different streams of applied sciences.
“…The successive bioassay for PTP1B activity for these glyconconjugates suggests that molecules containing carboxylic acid and benzyl moieties were the most potential PTP1B inhibitors (IC 50 = 5.6 μM for 580 and IC 50 = 5.5 μM for 581). 584 A class of mono-and bisphenylalaninyl and -tyrosinyl glucosides were recognized as PTP1B inhibitors by the Chen group. 585 Glucosyl scaffolds incorporated with one or two phenylalanine or tyrosine substituents on the 2,3-, 2,6-, 3,4-, 4,6-, and 6-positions were synthesized in excellent yields under MWassisted click chemistry.…”
Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC), popularly known as the "click reaction", serves as the most potent and highly dependable tool for facile construction of simple to complex architectures at the molecular level. Click-knitted threads of two exclusively different molecular entities have created some really interesting structures for more than 15 years with a broad spectrum of applicability, including in the fascinating fields of synthetic chemistry, medicinal science, biochemistry, pharmacology, material science, and catalysis. The unique properties of the carbohydrate moiety and the advantages of highly chemo- and regioselective click chemistry, such as mild reaction conditions, efficient performance with a wide range of solvents, and compatibility with different functionalities, together produce miraculous neoglycoconjugates and neoglycopolymers with various synthetic, biological, and pharmaceutical applications. In this review we highlight the successful advancement of Cu(I)-catalyzed click chemistry in glycoscience and its applications as well as future scope in different streams of applied sciences.
“…In 2011, Wang et al synthesized triazolyl phenylalanine and tyrosine-aryl C -glycoside hybrids via microwave-assisted Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition [ 77 ]. Successive enzymatic assay identified the synthesized glycoconjugates as novel PTP1B inhibitors with low micromole-ranged inhibitory activity and at least several-fold selectivity over other homologous PTPs tested.…”
Section: -Glycosides As Antidiabetic Agentsmentioning
confidence: 99%
“…Benzyl groups on glucosyl moiety of compounds were found crucial for PTP1B inhibition. The biological assay identified the glycoconjugates that contain the carboxylic acid and benzyl moieties as more active PTP1B inhibitors compared to their ester and debenzylated counterparts [ 77 ]. Scheme 47 Synthesis of triazolyl phenylalanine and tyrosine-aryl C -glycoside hybrids 300 via microwave-assisted Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition [ 77 ] …”
Section: -Glycosides As Antidiabetic Agentsmentioning
confidence: 99%
“… Synthesis of triazolyl phenylalanine and tyrosine-aryl C -glycoside hybrids 300 via microwave-assisted Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition [ 77 ] …”
Section: -Glycosides As Antidiabetic Agentsmentioning
This review is an effort to summarize recent developments in synthesis of
O
-glycosides and
N
-,
C
-glycosyl molecules with promising antidiabetic potential. Articles published after 2000 are included. First, the
O
-glycosides used in the treatment of diabetes are presented, followed by the
N
-glycosides and finally the
C
-glycosides constituting the largest group of antidiabetic drugs are described. Within each group of glycosides, we presented how the structure of compounds representing potential drugs changes and when discussing chemical compounds of a similar structure, achievements are presented in the chronological order.
C
-Glycosyl compounds mimicking
O
-glycosides structure, exhibit the best features in terms of pharmacodynamics and pharmacokinetics. Therefore, the largest part of the article is concerned with the description of the synthesis and biological studies of various
C
-glycosides. Also
N
-glycosides such as
N
-(β-
d
-glucopyranosyl)-amides,
N
-(β-
d
-glucopyranosyl)-ureas, and 1,2,3-triazolyl derivatives belong to the most potent classes of antidiabetic agents. In order to indicate which of the compounds presented in the given sections have the best inhibitory properties, a list of the best inhibitors is presented at the end of each section. In summary, the best inhibitors were selected from each of the summarizing figures and the results of the ranking were placed. In this way, the reader can learn about the structure of the compounds having the best antidiabetic activity. The compounds, whose synthesis was described in the article but did not appear on the figures presenting the structures of the most active inhibitors, did not show proper activity as inhibitors. Thus, the article also presents studies that have not yielded the desired results and show directions of research that should not be followed. In order to show the directions of the latest research, articles from 2018 to 2019 are described in a separate Sect.
5
. In Sect.
6
, biological mechanisms of action of the glycosides and patents of marketed drugs are described.
Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (Cue-AAC), which is the best paradigm of "Click Chemistry" philosophy that was initially coined by Sharpless and co-workers at the very beginning of the third millennium, has been demonstrated as a powerful tool in numerous scientific fields including medicinal chemistry, materials science, etc., due to its superior stereoselectivity, modularity and functional group tolerance. Meanwhile, microwave irradiation has attracted increasingly much attention as a highly effective and green synthetic complement as this technique can distinctly reduce the time consumption and simultaneously enhance the yields and purity of a diverse range of organic reactions in comparison with conventional heating methods. Herein, recent tactics that combine Cue-AAC with microwave irradiation technique toward the construction of useful bio-macromolecules and small molecule libraries are reviewed while the prospective with respect to the future development of this specific area is offered.
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