Abraham J. Brink

Synthesis of branched-chain sugars by reaction of glycosuloses with α-metalated isocyanoacetic esters1

Abstract Addition of ethyl isocyanoacetate in strongly basic medium to the glycosuloses 1,2:5,6-di- O -isopropylidene-α- d - ribo -hexofuranos-3-ulose ( 1 ) and 1,2- O -isopropylidene-5- O -trityl- d - erythro -pentos-3-ulose ( 2 ) gave the unsaturated derivatives ( E )- and ( Z )-3-deoxy-3- C -ethoxycarbonyl(formylamino)methylene-1,2:5,6-di- O -isopropylidene-α- d -glucofuranose ( 3 and 4 ), and ( E )-3-deoxy-3- C -ethoxycarbonyl(formylamino)methylene-1,2- O -isopropylidene-5- O -trityl-α- d -ribofuranose ( 5 ). In weakly basic medium, ethyl isocyanoacetate and 1 gave 3- C -ethoxycarbonyl(formylamino)methyl-1,2:5,6-di- O -isopropylidene-α- d -allofuranose ( 12 ) in good yield. The oxidation of 3 and 4 with osmium tetraoxide to 3- C -ethoxalyl-1,2:5,6-di- O -isopropylidene-α- d -glucofuranose ( 17 ), and its subsequent reduction to 3- C -( R )-1′,2′-dihydroxyethyl-1,2:5,6-di- O -isopropylidene-α- d -glucofuranose ( 18 ) and its ( S ) epimer ( 19 ) and to 3- C -( R )-ethoxycarbonyl(hydroxy)methyl-1,2:5,6-di- O -isopropylidene-α- d -glucofuranose ( 21 ) and its ( S ) epimer ( 22 ) are described. Hydride reductions of 12 yielded the corresponding 3- C -(1-formylamino-2-hydroxyethyl), 3- C -(2-hydroxy-1-methylaminoethyl), and 3- C -( R )-ethoxycarbonyl(methylamino)methyl derivatives ( 13 , 14 and 16 ). Catalytic reduction of 3 and 4 yielded the 3-deoxy-3- C -( R )-ethoxycarbonyl-(formylamino)methyl derivative 6 and its 3- C -( S ) epimer. Further reduction of 6 gave 3-deoxy-3- C -( R )-(1-formylamino-2-hydroxyethyl)-1,2:5,6-di- O -isopropylidene-α- d -allofuranose ( 23 ) which was deformylated with hydrazine acetate to 3- C -( R )-(1-amino-2-hydroxyethyl)-3-deoxy-1,2:5,6-di- O -isopropylidene-α- d -allofuranose ( 24 ). The configurations of the branched-chains in 16 , 21 , and 22 were determined by o.r.d.

Chain elongation of sugars with ethyl isocyanoacetate

Abstract Addition of ethyl isocyanoacetate to 3- O -benzyl-1,2- O -isopropylidene-α- D - ribo -pentodialdo-1,4-furanose in ethanolic sodium cyanide gave two oxazolines that were hydrolysed during chromatography to two isomeric ethyl 3- O -benzyl-6-deoxy-6-formamido-1,2- O -isopropylidene-heptofuranuronates. Similarly, 1,2- O -isopropyl-idene-3- O -methyl-α- D - xylo -pentodialdo-1,4-furanose gave the 3- O -methyl-heptofuranuronates 7 and 11 . Reduction of 7 and 11 gave N -methylamino esters that exhibited Cotton effects from which the configurations at C-6 of 7 and 11 were deduced. The chiralities at C-5 of 7 and 11 were established by tetrahydropyranlation of 7 and 11 , followed by consecutive treatment with bis(2-methoxyethoxy)aluminium hydride, periodate, sodium borohydride, and dilute acid, to give 1,2- O -isopropylidene-3- O -methyl-α- D -glucofuranose and its β- L - ido epimer, respectively. Attempts to methylate HO-5 of 7 and 11 resulted in elimination. On formylaminomethylenation (ethyl isocyanoacetate and potassium hydride in tetrahydrofuran), 3- O -benzyl-1,2- O -isopropylidene-α- D - ribo -pentodialdo-1,4-furanose and its 3- O -methyl-α- D - xylo epimer each gave ( E )- and ( Z )-mixtures of alkenes that were hydrogenated to give mixtures of 5,6-dideoxy-6-formamido-heptofuranuronates.

Synthesis of an analogue of the polyoxins: X-ray structure of starting carbohydrate and acetal migration accompanying acetolysis

Abstract An analogue of the polyoxins has been prepared from 1,5 - di - O - acetyl - 3 - C - (R) - ethoxycarbonylmethyl -5(R),1′(R) - N - formylepimino - 2,3 - O - isopropylidene - β - d - ribofuranose (13). The structure of 13 was determined by X-ray analysis. Intramolecular acetal migrations were observed during acetolysis under acid conditions.

2-C-nitrometnyl and 2-C-aminomethyl derivatives of D-ribose. Preparation of 2′-C-nitromethyluridines

Syntheses of derivatives of 2-C-nitromethyl-D-ribofuranose from a 3-C-nitromethyl-D-allofuranose are reported. The use of two of these compounds in nucleoside syntheses and their catalytic reduction, which takes place with acetyl migration, are discussed.

Preparation of analogues of the carbohydrate moiety of the polyoxins.

Syntheses of 2-C-[ethoxycarbonyl(formylamino)methylene] carbohydrate derivates by formylaminomethylenation of two pentofuranosulosides and a pentopyranosuloside are described. Hydrogenation of the unsaturated branched-chain compounds gave glycosides bearing protected amino-acid moieties as substituents at C-2. Hydrolysis and reduction experiments that establish the structures of the branched-chain compounds are described.

Synthesis of fluorinated branched-chain sugars

Treatment of (E)-3-deoxy-3-C-ethoxycarbonyl(formylamino)methylene-1,2 : 5,6-di-O-isopropylidene-α-D-glucofuranose with trifluoro(fluoro-oxy)methane gives branched-chain sugars bearing a fluorine atom at the branch point. Some reactions of these fluorinated sugars are described.

Cyano-sugars. Part 3. Synthesis of 2-C-cyano-2-deoxy-sugars from 2-C-cyano-galactals and attempts to prepare pentofuranosyl cyanides from aldonic acid lactones with tosylmethyl isocyanide

1,5-Anhydro-2-C-cyano-2-deoxy-D-lyxo-hex-1-enitol (2) reacted with sodium methoxide in methanol to give, after acetylation, methyl 3,4,6-tri-O-acetyl-2-C-cyano-2-deoxy-β-D-galactopyranoside (6) as the main product. Similar treatment of 1,5-anhydro-2-C-cyano-2-deoxy-1,2-O-isopropylidene-D-lyxo-hex-1-enitol (3) gave methyl 4,6-di-O-acetyl-2-C-cyano-2-deoxy-3-O-methyl-α-D- and -β-D-galactopyranoside (11) and (7), respectively, as the main products. Compounds (6), (7), and (11) were converted into their 2-C-acetamidomethyl analogues (8), (9), and (12), respectively, in high yield by catalytic hydrogenation in ethanol–acetic anhydride.The formylaminomethylenation of 2,3 : 5,6-di-O-isopropylidene-D-mannono-1,4-lactone with tosylmethyl isocyanide gave (E)- and (Z)-2,5-anhydro-1-deoxy-1-formylamino-3,4 : 6,7-di-O-isopropylidene-1-tosyl-D-manno-hept-1-enitol [(17) and (18)]. The reaction of the main isomer (17) with 2 equiv, of sodium ethoxide in ethanol, gave ethyl [(1R)-O-ethyl-1-formylamino-3,4 : 6,7-di-O-isoproyplidene-aldehydo-α-D-manno-heptafuranos]uloside and its (1S)-epimer [(21) and (22)], and not 2,3 : 5,6-di-O-isopropylidene-α,β-D-mannofuranosyl cyanide, as expected. 2,3 : 5,6-Di-O-isopropylidene-D-gulono-1,4-lactone behaved similarly.