Synthesis method of glucoside based on indoxyl derivative and 2-(benzothiazol-2'-yl)phenol derivative

Abstract

The invention discloses a synthesis method of glucoside based on an indoxyl derivative and a 2-(benzothiazol-2'-yl)phenol derivative. The general formula of a synthetic equation of the synthesis method is as shown in the description; the Ar-OH represents aromatic phenol or a ketonic compound thereof, and is used as a glycosyl receptor in a glycosylation reaction; the G-X represents halogenated sugar, and is used as a glycosyl donor in the glycosylation reaction. According to the synthesis method of the glucoside based on the indoxyl derivative and the 2-(benzothiazol-2'-yl)phenol derivative, a 1-acetylindolin-3-one derivative is selected and used as an intermediate; a novel synthesis method is researched and developed to prepare the glucoside based on the indoxyl derivative; a novel glycosidase fluorescence probe based on a BTP ((2-benzothiazol-2'-yl)phenyl) derivative is synthesized by applying the method; meanwhile, the application effects of the glucoside based on the indoxyl derivative and the glycosidase fluorescence probe are investigated. The glucoside based on the indoxyl derivative and the 2-(benzothiazol-2'-yl)phenol derivative can be used as glycosidase substrates, and is used for the positioning analytic detection and screening on the corresponding glycosidase, a microorganism using the corresponding glycosidase as a characteristic target, and the like.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, in particular to a method for synthesizing glycosides based on indoxyl derivatives and 2-(benzothiazol-2'-yl)phenol derivatives. Background technique [0002] Glycosidases, also known as O-glycoside hydrolases, are a group of enzymes widely distributed in nature that are responsible for catalyzing the hydrolysis of O-glycosidic bonds in carbohydrate and glycoconjugate molecules. These enzymes are among the most efficient enzymes found in nature; they catalyze the hydrolysis of glycosidic bonds at rates up to 10 17 times. With the exception of some archaea and some unicellular parasites, glycosidases are present in all living organisms and play a variety of roles. In prokaryotic organisms, glycosidases are present both intracellularly and extracellularly and are primarily involved in nutrient acquisition. In higher organisms, glycosidases are present in the endoplasmic reticulum and Golgi appa...

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Problems solved by technology

When using 1a, the glycosidation reaction is often carried out under the conditions of NaOH or KOH aqueous solution / acetone / 0°C, and the yield is quite low, especially for the preparation of glucoside derivatives; sometimes the Koenigs-Knorr method (silver trifluoromethanesulfonate, etc. catalyst), but the glycosyl donors used are not easy to prepare and are rarely used (Trends Carbohydr.Res., 2014, 6, 1-10; US Patent 7323488, 2008.); it has been reported that phase transfer catalysis has been tried It was used to study the glycosylation reaction of 1-acetyl-5-bromoindolin-3-one with acetylbromogalactose, but it was replaced by other methods due to the complexity of the reaction mixture and low yield (Mol.Imaging, 2008 ,7,187-197), thus, phase transfer catalysis is even considered infeasible (TrendsCarbohydr.Res.,2014,6,1-10.)

When using 1b, the glycosylation reaction needs to be strictly anaerobic and difficult to operate, there are many colored impurities, and the yield is low. In addition, because methanol is used as a solvent, the solubility of some glycosyl donors (such as polysaccharide donors) is not good, which is not conducive to glycosylation Reaction (US Patent 7323488,2008.)

When using 1c, the reaction route is tedious, the purification work is relatively more heavy, and the decarboxylation yield when R is Me is mostly lower than 50%, while the decarboxylation yield when R is Allyl is higher, but the decarboxylation pretreatment is more troublesome ( Org. Lett., 2013, 15, 3766-3769; Eur. J. Org. Chem., 2014, 564-574.)

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