Acid-catalysed rearrangement of acyl groups: synthesis of β-d-gluco aminocyclopentitols and carbanucleoside derivatives

Abstract

N-Benzyl-1,2,3-tri-O-benzyl-β-D-gluco aminocyclopentitol (8) displays anticancer activity, whereas β-D-gluco aminocyclopentitol (9) and its N-benzyl analogue (10) are potent glycosidase inhibitors. Acid-catalysed 1,2-acetonide deprotection of a D-glucose derived precursor featuring a vinyl functionality at C-4 and O-acyl group at C-3 produced latent aldehydes with the ester group moving between the C-2 and C-4 hydroxyl groups. Subsequent stereoselective intramolecular nitrone cycloaddition (INC) reactions yielded various desired cyclopentano-isoxazolidines, which, upon heterocyclic ring or N–O bond cleavage as the key step formed 9 and partially O-acetylated/benzoylated derivatives of 9 and 10, respectively. During the process, formal syntheses of 8 and 10 were also completed. Compound 9 and its dideoxy derivative 32, obtained through the Barton–McCombie deoxygenation reaction of the appropriate isoxazolidine, were elaborated to carbanucleoside derivatives having 6-chloropurine, hypoxanthine, and adenine as nucleoside bases.