Riaz Khan

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 .

Synthesis and reactions of tert-butyldiphenylsilyl ethers of sucrose☆

Abstract The reaction of sucrose with 1.1 mol. equiv. of tert-butyldiphenylsilyl (t-BDPS) chloride in pyridine in the presence of 4-dimethylaminopyridine gave the crystalline 6′-t-BDPS ether 1 in 49% yield, without recourse to column chromatography. Compound 1 was transformed into the 4,6,1′-trichloride by using sulphuryl chloride. When the silylation reaction of sucrose was performed with 3 mol. equiv. of the reagent, chromatography gave the crystalline 6,6′-di-t-BDPS ether and the 6,1′,6′-tri-t-BDPS ether 9 in yields of 78 and 18.7%, respectively. Compound 9 was obtained as the major product on treatment of sucrose with 4.6 mol. equiv. of the silylating reagent. Removal of the silyl protecting-group in 6,6′-di-O-tert-butyl-diphenylsilylsucrose hexabenzoate, using tetrabutylammonium fluoride, proceeded smoothly, but with 4→6 migration of the benzoate.

Hydroformylation catalysed by rhodium complexes of trehalose-derived ligands aa and ββ-tredip; a highly recioselective route to α-methylarylpropionaldehydes

Abstract Rhodium complexes of the ligand αα -TREDIP give 62:1 iso -regioselectivity in the hydroformylation of styrene under ambient conditions without excess phosphine, higher than any previously reported value. The results are compared with those obtained with other ligands, and extended to the preparation of 2-(6-methoxy-2-naphthyl)-propanal, a precursor of the anti-inflammatory drug naproxen.

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) .

The first replacement of a chlorosulphonyloxy group by chlorine at C-2 in methyl α-D-glucopyranoside and sucrose derivatives☆

Abstract Treatment of methyl 3- O -acetyl-4,6- O -benzylidene-α- D -glucopyranoside 2-chlorosulphate ( 2 ), 3,4,6,3′,4′,6′-hexa- O -acetylsucrose 2,1′-bis(chlorosulphate), 3,4,6,3′,4′,6′-hexa- O -acetyl-1′- O -benzoylsucrose 2-chlorosulphate, and 3,4,3′,4′-tetra- O -acetyl-6,6′-dichloro-6,6′-dideoxysucrose 2,1′-bis(chlorosulphate) with lithium chloride in hexamethylphosphoric triamide gave the corresponding chlorodeoxy- manno derivatives. Treatment of the 2-chlorosulphate 2 with such nucleophilic reagents as lithium bromide, sodium azide, sodium chloride, and sodium benzoate in hexamethylphosphoric triamide gave the 2-hydroxy compound as a major product. Selective chlorination at C-1′ was achieved when 3,4,6,3′,4′,6′-hexa- O -acetylsucrose was treated with sulphuryl chloride in a mixture of pyridine and chloroform.

Tin(IV)-functionalised polymer supports; non-toxic and practical reagents for regioselective acetylation of sucrose

Polymer-supported butyltin(IV) reagents have been surveyed for regioselectivity in acetylation of sucrose. Polymer-supported butyltin(IV) dichloride 8 catalysed the acetylation of sucrose to give a 59% yield of 6-O-acetyl sucrose 3, the precursor of sucralose. The yield is close to that of a previously reported process involving dibutyltin(IV) oxide (Bu2SnO). The spent polymeric resin could readily be regenerated and can be subsequently used in further synthetic reactions.

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.

A Simple Route to β,β-Trehalose via Trichloroacetimidates

Abstract The reaction of 2,3,4,6-tetra-O-acetyl-β-D-glucopyranose with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl trichloroacetimidate in CH2Cl2 promoted by BF3;OEt2 gives β,β-octaacetyltrehalose in up to 58% isolated yield, which is readily deacetylated to β,β-trehalose. The corresponding 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl penta-fluorophenylimidate is configurationally stable and inert to coupling under mild conditions.

Synthesis of 6-O-methotrexylhyaluronan as a drug delivery system

Selective halogenation of hyaluronan and partial halogen substitution by methotrexate led to 6-chloro-6-deoxy-6-O-methotrexylhyaluronan, a potential antitumor drug. The remaining halogen could be further substituted by a second organic carboxylate, leading to mixed esters. 6-O-Acetyl-6-O-methotrexylhyaluronan and 6-O-butyryl-6-O-methotrexylhyaluronan were thus synthesized and characterized by NMR spectroscopy.

Synthesis and reactions of cyclic acetal derivatives of 6,6′-dichloro-6,6′-dideoxysucrose☆

Abstract Treatment of 6,6′-dichloro-6,6′-dideoxysucrose with a combination of 2,2-dimethoxypropane, N,N -dimethylformamide, and toluene- p -sulphonic acid (reagent A), followed by acetylation, gave the 1′,2:3,4-diacetal 1 (39%) and the 1′,2-acetal 2 (37%). A similar reaction of methyl 6-chloro-6-deoxy-α- D -glucopyranoside with reagent A yielded the corresponding 2,3- and 3,4-acetal derivatives in yields of 29% and 9%, respectively. The structures of 1 and 2 have been confirmed by 1 H-n.m.r. spectroscopy and by chemical transformations.