Khizar Sultan Mufti

Synthesis and reactions of 1′,2:4,6-di-o-isopropylidene-sucrose

Abstract The reaction of sucrose with a combination of 2,2-dimethoxypropane, N,N -dimethylformamide, and toluene- p -sulphonic acid (reagent A ) gave, after acetylation followed by chromatography, 1′,2:4,6-di- O -isopropylidenesucrose tetra-acetate ( 1 ) in 15% yield. The structure of 1 was determined on the basis of p.m.r. and mass spectrometry, and by chemical transformations. Treatment of 1 with aqueous acetic acid afforded sucrose 3,3′,4′,6′-tetra-acetate 2. Reacetalation of 2 using reagent A gave 1 in 80% yield. The p.m.r. spectrum of 2 confirmed the presence of hydroxyl groups at C-2 and C-4. The following sequence of reactions showed that the remaining two hydroxyl groups were located at C-6 and C-1′. Selective tritylation of 2 gave 1′,6-di- O -tritylsucrose 3,3′,4′,6′-tetra-acetate ( 3 ) as the minor, and 6- O -tritylsucrose 3,3′,4′,6′-tetra-acetate ( 4 ) as the major, product. When tritylation was carried out under forcing conditions, 2 gave 3 as the major product. Acetylation of 4 afforded 6- O -tritylsucrose hepta-acetate. Mesylation of 2 gave the tetramethanesulphonate 5 , which afforded the 6-dcoxy-6-iodo derivative 6 on treatment with a refluxing solution of sodium iodide in butanone. Treatment of 3 with methanesulphonyl chloride in pyridine gave the disulphonate 7 , which on detritylation followed by acetylation gave 2,4-di- O -methanesulphonylsucrose hexa-acetate ( 9 ). Treatment of 9 with sodium benzoate in hexamethylphosphoric triamide displaced the 4-sulphonate, with inversion of configuration, to give the galacto derivative 10 .

Reaction of methanesulphonyl chloride-N,N-dimethylformamide with partially esterified derivatives of sucrose

Abstract Treatment of sucrose 2,3,3′,4′,6-penta-acetate (1) with methanesulphonyl chloride- N,N -dimethylformamide (reagent A ) gave the 1′,4,6′-trichloride 2 , the 1′- O -formyl-4,6′-dichloride 3 , the 4,6′-dichloride 4 , and the 1′,4-di- O -formyl-6′-chloride 5 . De-esterification of 3 afforded the unsubstituted 4,6′-dichloride 6 which, on acetylation, gave the corresponding hexa-acetate 7 , also prepared by acetylation of 4 . In compounds 2, 3, and 4, substitution at C-4 by chloride ion occurred with inversion of configuration. The structure of 5 was confirmed by conversion into the known 6′chloro-6′-deoxysucrose hepta-acetate by de-esterification followed by acetylation. Treatment of sucrose 1′,2,3,3′,4′,6′-hexa-acetate (10) with the reagent gave the 4,6-dichloride 11 and 4- O -formyl-6-chloride 12 . The formyl group in 12 was selectively removed by using an anion-exchange resin to give 16 . De-esterification of 12 with methanolic sodium methoxide gave 6-chloro-6-deoxysucrose (13) which, on acetylation and benzoylation, afforded the hepta-acetate 14 and the hepta-benzoate 15, respectively. Alternatively, 15 was prepared by the reaction of 1′,2,3,3′,4,4′,6′-hepta- O -benzoylsucrose with reagent A . Treatment of 14 with sodium methoxide in methanol followed by acetylation gave 3,6-anhydrosucrose hexa-acetate (24) . Reaction of sucrose 2,3,3′,4,4′-pentabenzoate (17) with reagent A gave the known 1′,6,6′-trichloro-1′,6,6′-trideoxysucrose pentabenzoate (18) and 1′- O -formyl-6,6′-dichloride 19 . Treatment of 19 with anion-exchange resins selectively removed the formyl group to give 20 . The structure of 20 was confirmed by conversion into the 1′-chlorosulphate-6,6′-dichloride (21) . Treatment of sucrose 1′,2,3,3′,4,4′-hexabenzoate (22) with reagent A gave the expected 6,6′-dichloride (23) .

Ring-opening reactions of sucrose epoxides: Synthesis of 4′-derivatives of sucrose☆

Abstract The 2,1′- O -isopropylidene derivative ( 1 ) of 3- O -acetyl-4,6- O -isopropylidene-α- d -glucopyranosyl 6- O -acetyl-3,4-anhydro-β- d - lyxo -hexulofuranoside and 2,3,4-tri- O -acetyl-6- O -trityl-α- d -glucopyranosyl 3,4-anhydro-1,6-di- O -trityl-β- d - lyxo -hexulofuranoside have been synthesised and 1 has been converted into 2,3,4,6-tetra- O -acetyl-α- d -glucopyranosyl 1,6-di- O -acetyl-3,4-anhydro-β- d - lyxo -hexulofuranoside ( 2 ). The S N 2 reactions of 2 with azide and chloride nucleophiles gave the corresponding 2,3,4,6-tetra- O -acetyl-α- d -glucopyranosyl 1,3,6-tri- O -acetyl-4-azido-4-deoxy-β- d -fructofuranoside ( 6 ) and 2,3,4,6-tetra- O -acetyl-α- d -glucopyranosyl 1,3,6-tri- O -acetyl-4-chloro-4-deoxy-β- d -fructofuranoside ( 8 ), respectively. The azide 6 was catalytically hydrogenated and the resulting amine was isolated as 2,3,4,6-tetra- O -acetyl-α- d -glucopyranosyl 4-acetamido-1,3,6-tri- O -acetyl-4-deoxy-β- d -fructofuranoside. Treatment of 5 with hydrogen bromide in glacial acetic acid followed by conventional acetylation gave 2,3,4,6-tetra- O -acetyl-α- d -glucopyranosyl 1,3,6-tri- O -acetyl-4-bromo-4-deoxy-β- d -fructofuranoside. Similar S N 2 reactions with 2,3,4,6-tetra- O -acetyl-α- d -glucopyranosyl 1,6-di- O -acetyl-3,4-anhydro-β- d - ribo -hexulofuranoside ( 12 ) resulted in a number of 4′-derivatives of α- d -glucopyranosyl β- d -sorbofuranoside. The regiospecific nucleophilic substitution at position 4′ in 2 and 12 has been explained on the basis of steric and polar factors.

Synthesis and ring-opening reactions of 4-chloro-4-deoxy-α-d-galactopyranosyl 3,4-anhydro-1,6-dichloro-1,6-dideoxy-β-d-lyxo-hexulofuranoside

Abstract Treatment of 4-chloro-4-deoxy-α- d -galactopyranosyl 1,6-dichloro-1,6-dideoxy-β- d -fructofuranoside ( 1 ) with 2.3 mol. equiv. of diethyl azodicarboxylate (DEAD) and 1.3 mol. equiv. of triphenylphosphine (TPP) in toluene gave a mixture of 3,6-anhydro-4-chloro-4-deoxy-α- d -galactopyranosyl 3,4-anhydro-1,6-dichloro-1,6-dideoxy-β- d - lyxo -hexulofuranoside ( 2 , 55%) and 4-chloro-4-deoxy-α- d -galactopyranosyl 3,4-anhydro-1,6-dichloro-1,6-dideoxy-β- d - lyxo -hexulofuranoside ( 3 , 35%). Compound 3 was also synthesised from 6- O - tert -butyldiphenylsilyl-4-chloro-4-deoxy-α- d -galactopyranosyl 1,6-dichloro-1,6-dideoxy-β- d -fructofuranoside by epoxidation with DEAD-TPP and removal of the silyl ether group with tetrabutylammonium fluoride. The S N 2 reactions of 2,3,6-tri- O -acetyl-4-chloro-4-deoxy-α- d -galactopyranosyl 3,4-anhydro-1,6-dichloro-1,6-dideoxy-β- d - lyxo -hexulofuranoside ( 5 ) with fluoride, chloride, bromide, iodide, and azide ions gave the corresponding 4′-derivatives 10 , 12 , 14 , 18 , and 20 , respectively. Reduction of 4-chloro-4-deoxy-α- d -galactopyranosyl 4-bromo-1,6-dichloro-1,4,6-trideoxy-β- d -fructofuranoside ( 15 ) gave 4-chloro-4-deoxy-α- d -galactopyranosyl 1,6-dichloro-1,4,6-trideoxy-β- d -fructofuranoside ( 16 ). A similar reduction of 4-chloro-4-deoxy-α- d -galactopyranosyl 4-azido-1,6-dichloro-1,4,6-trideoxy-β- d -fructofuranoside ( 21 ) gave 4-chloro-4-deoxy-α- d -galactopyranosyl 4-amino-1,6-dichloro-1,4,6-trideoxy-β- d -fructofuranoside ( 22 ).