Polyhydroxylated pyrrolidines: synthesis from d-fructose of new tri-orthogonally protected 2,5-dideoxy-2,5-iminohexitols

Abstract

The readily available 3- O-benzyl-1,2- O-isopropylidene-β- d-fructopyranose ( 2) was transformed into its 5- O- ( 3) and 4- O-benzoyl ( 4) derivative. Compound 4 was straightforwardly transformed into 5-azido-4- O-benzoyl-3- O-benzyl-5-deoxy-1,2- O-isopropylidene-β- d-fructopyranose ( 7) via the corresponding 5-deoxy-5-iodo-α- l-sorbopyranose derivative 6. Cleavage of the acetonide in 7 to give 8, followed by regioselective 1-O-silylation to 9 and subsequent catalytic hydrogenation gave a mixture of (2 S,3 R,4 R,5 R)- ( 10) and (2 R,3 R,4 R,5 R)-4-benzoyloxy-3-benzyloxy-2′- O- tert-butyldiphenylsilyl-2,5-bis(hydroxymethyl)pyrrolidine ( 12) that was resolved after chemoselective N-protection as their Cbz derivatives 11 and 1a, respectively. Stereochemistry of 11 and 1a could be determined after total deprotection of 11 to the well known DGDP ( 13). Compound 2 was similarly transformed into the tri-orthogonally protected DGDP derivative 18.