Indoxylic Acid Esters as Convenient Intermediates Towards Indoxyl Glycosides

Böttcher, Stephan; Thiem, Joachim

doi:10.1002/ejoc.201301198

Cited by 14 publications

(8 citation statements)

References 24 publications

(36 reference statements)

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“…Surprisingly, 5,7-dibromoisatin (5) [32,33] was not produced during this reaction. The 1 H, 13 C NMR spectra of 6 confirmed the proposed structure and were in accordance with those reported in the literature [34][35][36]. On the other hand, the use of 1 equivalent of NBS in the reaction with isatin, at the same reaction conditions, resulted in the formation of 5-bromoisatin (4) in good yield.…”

Section: Resultssupporting

confidence: 90%

Synthesis and biological evaluation of some amino- and sulfanyl-3H-quinazolin-4-one derivatives as potential anticancer agents

et al. 2015

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A series of 6-substituted quinazolinone derivatives were prepared by the reaction of 6-bromoquinazolinones with aryl or alkyl amines and thiols, in the presence of a Pd(OAc) 2 /Xantphos system, under Buchwald-Hartwig-type reaction conditions. The 6-bromoquinazolinones were obtained in the three-components reaction of 5-bromoisatoic anhydride, triethyl orthoformate and an appropriate amine. Biological screening of the potential cytotoxicity of synthesized compounds on HT29 and HCT116 cell lines, as well as on the lymphocytes, showed that some derivatives of quinazolinone have significant anticancer activities. The detailed synthesis, spectroscopic data, and biological assays were reported. Graphical abstract

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Section: Resultssupporting

confidence: 90%

Synthesis and biological evaluation of some amino- and sulfanyl-3H-quinazolin-4-one derivatives as potential anticancer agents

et al. 2015

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“…First among them were the structural analogy of 8 and 9 to X-Gal 5 and reports on methods for the synthesis and utilization of indolyl glycosides in glycosidase assays [ 17 ]. The substitution pattern on the 5-bromo-3-indolyl aglycone was based on the ready availability of the 5-bromo-anthranilic acid starting material and the color of tyrian purple dye (an analog of 7 lacking the chlorine atoms) that arises from its oxidative dimerization [ 18 , 19 ]. Further, the stereogenic centers from C3-C6 in β-configured d - glycero - d - gulo -septanoside 8 and d - glycero - d - ido -septanoside 9 have identical relative configurations as D-glucose from C2-C5.…”

Section: Resultsmentioning

confidence: 99%

“…We also considered the possible promiscuity of glucosidases as giving us a higher probability of identifying active GHs in our search. The synthetic strategy drew from reported methods for indolyl glycoside synthesis [ 18 , 23 , 24 , 25 ] and our previous experience at preparing septanose glycosides via nucleophilic displacement on anomeric bromides [ 26 ]. It leveraged a synthesis of the per- O -acetyl septanose precursors of the anomeric bromides that began from natural D-pyranosides such as D-glucose, suggesting that the route could be extended to other sugars.…”

Section: Resultsmentioning

confidence: 99%

Indolyl Septanoside Synthesis for In Vivo Screening of Bacterial Septanoside Hydrolases

Testolin

Pascual

Planas

et al. 2021

IJMS

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Building-up and breaking-down of carbohydrates are processes common to all forms of life. Glycoside hydrolases are a broad class of enzymes that play a central role in the cleavage of glycosidic bonds, which is fundamental to carbohydrate degradation. The large majority of substrates are five- and six-membered ring glycosides. Our interest in seven-membered ring septanose sugars has inspired the development of a way to search for septanoside hydrolase activity. Described here is a strategy for the discovery of septanoside hydrolases that uses synthetic indolyl septanosides as chromogenic substrates. Access to these tool compounds was enabled by a route where septanosyl halides act as glycosyl donors for the synthesis of the indolyl septanosides. The screening strategy leverages the known dimerization of 3-hydroxy-indoles to make colored dyes, as occurs when the β-galactosidase substrate X-Gal is hydrolyzed. Because screens in bacterial cells would enable searches in organisms that utilize heptoses or from metagenomics libraries, we also demonstrate that septanosides are capable of entering E. coli cells through the use of a BODIPY-labeled septanoside. The modularity of the indolyl septanoside synthesis should allow the screening of a variety of substrates that mimic natural structures via this general approach.

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“…Glycosylation in acetone/ sodium hydroxide, following deprotection and decarboxylation (160 °C, acetic anhydride, 1 hr) and finally deacetylation yielded Indicane and 5-bromo-indicane. Based on this concept we developed an improved synthesis of indoxyl glycosides, employing indoxylic acid allyl esters as acceptors [17][18][19] . The acceptor synthesis starts with the respective substituted aniline derivative (5) (Figure 2).…”

Section: Representative Resultsmentioning

confidence: 99%

Synthesis of Indoxyl-glycosides for Detection of Glycosidase Activities

Böttcher

Thiem

2015

JoVE

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Indoxyl glycosides proved to be valuable and versatile tools for monitoring glycosidase activities. Indoxyls are released by enzymatic hydrolysis and are rapidly oxidized, for example by atmospheric oxygen, to indigo type dyes. This reaction enables fast and easy screening in vivo without isolation or purification of enzymes, as well as rapid tests on agar plates or in solution (e.g., blue-white screening, micro-wells) and is used in biochemistry, histochemistry, bacteriology and molecular biology. Unfortunately the synthesis of such substrates proved to be difficult, due to various side reactions and the low reactivity of the indoxyl hydroxyl function. Especially for glucose type structures low yields were observed. Our novel approach employs indoxylic acid ester as key intermediates. Indoxylic acid esters with varied substitution patterns were prepared on scalable pathways. Phase transfer glycosylations with those acceptors and peracetylated glycosyl halides can be performed under common conditions in high yields. Ester cleavage and subsequent mild silver mediated glycosylation yields the peracetylated indoxyl glycosides in high yields. Finally deprotection is performed according to Zemplén. Video LinkThe video component of this article can be found at

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Indoxylic Acid Esters as Convenient Intermediates Towards Indoxyl Glycosides

Cited by 14 publications

References 24 publications

Synthesis and biological evaluation of some amino- and sulfanyl-3H-quinazolin-4-one derivatives as potential anticancer agents

Synthesis and biological evaluation of some amino- and sulfanyl-3H-quinazolin-4-one derivatives as potential anticancer agents

Indolyl Septanoside Synthesis for In Vivo Screening of Bacterial Septanoside Hydrolases

Synthesis of Indoxyl-glycosides for Detection of Glycosidase Activities

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