Versatile Routes to C-2- and C-6-Functionalized Glucose Derivatives of Iminodiacetic Acid

Abstract

A series of novel d-glucose derivatives, functionalized at the C-2 or the C-6 position with an iminodiacetic acid moiety for transition-metal complexation, has been prepared. The sugar and the metal-chelating parts are separated by either propyl or octyl chains and were introduced by the reaction of bromoalkylamine. Either N-1-Boc-3-bromopropylamine (17) or N-(8-bromooctyl)phthalimide (19) reacted with methyl 3,5,6-tri-O-benzyl-α-β-d-glucofuranoside (4) (C-2 position) and 1,2:3,5-(O-methylene)-α-d-glucose (11) (C-6 position), respectively, in the presence of sodium hydride in DMF at room temperature, affording the desired intermediates. For aminopropyl derivatives, yields varied between 57% and 65%, and for aminooctyl derivatives, yields varied between 40% and 71%. After deprotection of the amine functionality, the metal chelate was built up by dialkylation (6a − c and 13a,b) with methyl bromoacetate in the presence of triethylamine under reflux in THF. Yields varied between 56% and 69% for the glucose modified at the C-2 position and between 58% and 62% for the one modified at the C-6 position. All compounds were characterized by 1H or 13C NMR or both, IR, and mass spectroscopy. Final products were isolated as a mixture of α and β anomers.

Synthesis of O-1–O-6 Substituted Positional Isomers of d-Glucose–Thioether Ligands and Their Ruthenium Polypyridyl Conjugates

“…We therefore devised a new protecting group strategy improving the 10-step, 5% yield procedure published by Lippard et al 14 and employing the α-oxirane method developed by the group of Danishefsky 35 , 36 and attempted by Dumas et al ( Scheme 5 ). 31 Using this method, d -glucal was protected using the p -methoxy benzyl (PMB) group, affording 34 . Treatment of this compound with freshly prepared dimethyldioxirane (DMDO) afforded its corresponding 1,2-anhydrosugar, which was then condensed with p -methoxy benzyl alcohol (PMB–OH) in the presence of anhydrous ZnCl 2 in THF, affording β-substituted 35 , while simultaneously liberating the 2- O position.…”

“…This conversion proceeded smoothly, which is in contrast to the observation of Schubiger et al, who had to divert to the furanoside approach due to difficulties encountered during the installment of their iminodiacetic acid-based spacer. 31 With compound 36 in hand, a recently described method 37 using 37% hydrochloric acid in hexafluoroisopropanol (HFIP) was used to remove all four PMB groups simultaneously. After the reaction was quenched using Et 3 N ,an intermediate species was observed ( m / z = 463.4 found, 463.2 calcd) corresponding to the desired product H37 and a PMB group.…”

Carbohydrate‐Based Molecules for Molecular Imaging in Nuclear Medicine

“…Related 1‐ O ‐glycosylations67d,67l and 1‐ S ‐glycosylations67i,67l were pursued for further conjugation to the ligand. Other routes to D ‐glucose derivatives of IDA functionalized at C‐2, C‐3, and C‐6 have also been established 67f,70…”

Diagnostic Nuclear Medicine

“…Henry et al 1995;Dumas et al 2001Dumas et al , 2003, at this moment no sugar derivative labeled with either 123 I or 99m Tc is available as a SPET substitute for 18 F-FDG.…”