Synthesis of a 1,2-<i>cis</i>-indoxyl galactoside as a chromogenic glycosidase substrate

Nagata, Sakuto; Tomida, Hirotaka; Iwai-Hirose, Haruka; Tanaka, Hidenori; Ando, Hiromune; Imamura, Akira; Ishida, Hideyuki

doi:10.1039/c9ra05797h

Cited by 4 publications

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References 24 publications

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“…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%

“…The combined organic layers were dried over Na 2 SO 4 , filtered, and the solvent was evaporated under reduced pressure. The crude product was then purified by column chromatography to deliver 20 as brownish oil (0.0028 g, 48% yield) R f 0.4 (3:2 Hex: EtOAc); 1 H NMR (400 MHz, CDCl 3 ) δ 7.09 (s, 1H), 6.88 (d, J = 3.9 Hz, 1H), 6.28 (d, J = 4.0 Hz, 1H), 6.12 (s, 1H), 5.82 (broad s, 1H), 5.40 (dd, J = 8.0, 1.9 Hz, 2H), 5.34 (dd, J = 8.0, 3.9 Hz, 2H), 5.10 (dd, J = 6.5, 1.9 Hz, 2H), 5.05-5.00 (m, 2H), 4.18-4.12 (m, 3H), 3.28 (t, J = 7.5 Hz, 2H), 2.67-2.63 (m, 2H), 2.57 (s, 3H), 2.26 (s, 3H), 2.12 (s, 3H), 2.11 (s, 9H), 2.09 (s, 3H); 13 BODIPY: β-D-glycero-D-gulo-septanosyl azide conjugate (23). A solution of starting per-O-acetylated BODIPY conjugate 22 (0.0028 g, 0.004 mmol) was dissolved in dry methanol (0.75 mL) and kept under an inert atmosphere and dark conditions.…”

Section: Synthesis Of Indolyl Septanosides 8 Andmentioning

confidence: 99%

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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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