One-Pot Synthesis of Water-Soluble Glycosyl Azobenzenes and Their Photoswitching Properties in Water

Abstract

Molecular photoswitches capable of reversible photoswitching in aqueous media are highly demanded for various biological applications and photopharmacology. Carbohydrates, as natural and abundant raw materials, provide opportunity to make photoswitches water-soluble through linking sugar to the photoswitching molecules. We have developed a one-pot synthesis method to prepare water-soluble glycosyl azobenzenes through DMC (2-chloro-1,3-dimethylimidazolinium chloride)-mediated glycosylation between sugar and dihydroxyazobenzenes (DHABs) in aqueous media. The scope of the method has been investigated with different mono- and disaccharides, as well as with p,p′- and o,o′-DHAB, with excellent 1,2-trans stereoselectivity. Diglycosylation products can also be obtained with an excess amount of monosaccharides in one step. We have also demonstrated the possibility of further functionalization on the azobenzene moiety of glycosyl azobenzene. Both mono- and diglycosyl azobenzenes showed excellent photoswitching properties in water with high fatigue resistance and good thermostability for the Z-isomers. Excellent E → Z photoisomerization of both mono- and diglycosylated azobenzenes (Z/E = 99/1) is observed under illumination at 365 nm, while back Z → E photoisomerization can be achieved with blue light (with E/Z = 80/20 at PSS485 for the diglycosyl derivative).

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

“…The β- O -galactosyl p , p' -bis-substituted azobenzene derivative 1 was prepared from galactose and commercially available p , p’ -dihydroxyazobenzene ( 6 ), by using our recently developed DMC (2-chloro-1,3-dimethylimidazolinium chloride)-mediated one-pot glycosylation method in water [ 28 ], followed by O -alkylation of the remaining hydroxy group with BrCH 2 CH 2 NHBoc and acidic deprotection ( Scheme 1 ). Three equivalents of dihydroxyazobenzene 6 were used for the selective monoglycosylation step, with the excess of azobenene being recovered after column chromatography.…”

“…Three equivalents of dihydroxyazobenzene 6 were used for the selective monoglycosylation step, with the excess of azobenene being recovered after column chromatography. Under these conditions, no bisglycosylated azobenzene was observed [ 28 ]. The observed 1,2- trans glycosylation could be explained either by the formation of the 1,2-anhydro sugar through intramolecular attack of the 2-hydroxy group of the DMC-activated β-intermediate, followed by dihydroxyazobenzene attacking the anomeric center in an S N 2 manner, or by direct nucleophilic S N 2 attack on the DMC-activated α-intermediate, to produce the corresponding β- O -galactoside [ 36 ].…”

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

“…However, direct photo modulation of monovalent lectin ligand has not been achieved up to date. Based on our experiences in photoswitchable glycosides and bacterial lectins, [4,[6][7][8][24][25][26][27][28][29] we have designed, synthesized and characterized the first generation of O-and S-galactosyl azobenzenes as photoswitchable monovalent ligands targeting PA LecA. Their binding affinity with LecA evaluated by isothermal titration calorimetry (ITC) showed Kd values in micromolar range with significant thermodynamics difference between E-and Z-azobenzene isomers, demonstrating the proofof-concept of photomodulation of the ligand-lectin interactions.…”

“…The β-O-galactosyl p,p-bis-substituted azobenzene derivative 1 was prepared from galactose and commercially available p,p'-bishydroxy azobenzene 6, by using our recently developed DMC (2-chloro-1,3-dimethylimidazolinium chloride)-mediated one-pot glycosylation method in water, [26] followed by O-alkylation of the remaining hydroxyl group with BrCH2CH2NHBoc and acidic deprotection (Scheme 1). 3 equivalents of bishydroxy azobenzene 6 were used for the selective mono-glycosylation step, with the excess of azobenene being recovered after column chromatography.…”

“…The solution was neutralized using Amberlite IR-120 (H), filtered, concentrated and used without further purification to give the product in quantitative yield. (E)-4-[4′-(2-tert-Butyloxycarbonylaminoethyloxy)-phenylazo)phenyl-β-D-galactopyranoside (E-8): From 7 [26] (100 mg, 0.26 mmol) and BocNHCH2CH2Br (87 mg, 0.39 mmol), K2CO3 (72 mg, 0.52 mmol) according to the General procedure I, compound 8 (123 mg, 91%) was isolated as a yellow solid. Rf = 0.…”