ChemInform Abstract: Facile Syntheses of Galacto‐ and Glucopyranosyl Azides Substituted at C‐6.

Abstract

Acetylated 6‐iodo, 6‐bromo, 6‐chloro, and 6‐azido glucopyranosyl azides (IV) or (V) are obtained by nucleophilic displacement reactions of the tosylates (IIa) or (IIb), resp., which, in turn, are readily accessible from the anomeric azides (Ia), (Ib).

18F-Glyco-RGD Peptides for PET Imaging of Integrin Expression: Efficient Radiosynthesis by Click Chemistry and Modulation of Biodistribution by Glycosylation

“…Based on our previous work on the comprehensive carbohydrate chemistry of glycosyl precursors, including 1a , we envisaged the synthesis of an extended series of glycosyl azides 1b – 1f bearing a tosylate leaving group for nucleophilic 18 F-substitution in 6-position of the carbohydrate (Figure ). Employing classical synthetic methods, such as acetylation and deacetylation steps, fluorination by diethylaminosulfur trifluoride (DAST), and anomeric azido-for-bromo substitution reactions, − we achieved the synthesis of the labeling precursors 1b – 1f , following the route of the synthesis shown in Figure .…”

“…To this end we synthesized five tosyl or nosyl containing glycosyl-azides as 18 F-labeling precursors and examined the binding of the corresponding series of fluoroglycosyl peptides in vitro and the biodistribution properties in vivo . The synthesis of the labeling precursors were easily achieved by reaction of glucose, galactosylazide, maltosyl azide, or cellobiosyl azide, respectively, with tosyl or nosyl chloride in pyridine and subsequent acetylation using acetic anhydride . After column chromatography, the labeling precursors were obtained as pure β-anomers.…”

“…The synthesis of the labeling precursors were easily achieved by reaction of glucose, galactosylazide, maltosyl azide, or cellobiosyl azide, respectively, with tosyl or nosyl chloride in pyridine and subsequent acetylation using acetic anhydride. 23 After column chromatography, the labeling precursors were obtained as pure β-anomers. The 18 F-labeling was performed using mild reaction conditions with a lower amount of K 2 CO 3 in the presence of KH 2 PO 4 compared to commonly used 18 F-labeling conditions.…”

“…The synthesis was performed according to the procedure described in the literature . To a solution of p -toluenesulfonyl chloride (465 mg, 2.44 mmol) in anhydrous pyridine (7 mL) at 0 °C β-galactosyl azide (500 mg, 2.44 mmol; Sigma-Aldrich) was added, and the solution was stirred overnight at 0 °C.…”

“…The synthesis was performed according to the procedure described in the literature. 23 To a solution of p-toluenesulfonyl chloride (465 mg, 2.44 mmol) in anhydrous pyridine (7 mL) at 0 °C β-galactosyl azide (500 mg, 2.44 mmol; Sigma-Aldrich) was added, and the solution was stirred overnight at 0 °C. Acetic anhydride (2 mL) was added dropwise at 0 °C and the solution was stirred for 1 h. The solution was diluted with dichloromethane, and the organic phase was washed several times with saturated NaHCO 3 , 0.2 M HCl, and water, dried with Na 2 SO 4 , and concentrated to afford the crude product 1c which was crystallized from absolute EtOH: 350 mg, 730 μmol, 30% yield.…”