Amor Jordaan

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 C-glycosyl compounds. Part 1. Reaction of ethyl isocyanoacetate with 2,3:5,6-di-O-isopropylidene-D-mannono-1,4-lactone

Formylaminomethylenation of 2,3:5,6-di-O-isopropylidene-D-mannono-1,4-lactone (1) with ethyl isocyanoacetate (2) gave, as the major product, (E)-ethyl 3,6-anhydro-2-deoxy-2-formylamino-4,5:7,8-di-O-isopropylidene-D-manno-oct-2-enonate (3)(58%), which on hydrogenation gave ethyl 3,6-anhydro-2-deoxy-2-formylamino-4,5:7,8-di-O-isopropylidene-D-erythro-L-gluco-octonate (17), in almost quantitative yield. Base-catalysed equilibration of the D-erythro-L-gluco-octonate (17) gave a mixture of the L-allo-, L-altro-, L-gluco-, and L-manno-epimers [(23), (22), (17), and (19), respectively]. The configurations at C-2 and C-3 of these epimers were established by chemical and physical methods.The D-erythro-L-gluco-epimer (17) and the D-erythro-L-manno-epimer (19) were degraded to ethyl 3,6-anhydro-2-deoxy-2-formylamino-4,5-O-isopropylidene-D-glycero-L-gluco-heptonate (37) and its D-glycero-L-manno-epimer (39), respectively. Acidic hydrolysis of compounds (17), (19), (37), and (39) gave the free amino-acids, L-2-(β-D-mannofuranosyl)-glycine (41), the analogous D-amino-acid (42), L-2-(β-D-lyxofuranosyl)-glycine (43), and the analogous D-amino-acid (44), in moderate yields.In the presence of base, alcohols and thiols readily attacked the double bond of the oct-2-enonate (3) to give, for example, ethyl (ethyl 2-deoxy-2-formylamino-4,5:7,8-di-O-isopropylidene-α-D-manno-D-glycero-oct-3-ulo-3,6-furanosid)onate and its D-manno-L-glycero-epimer [(9) and (10)].

Some reactions of furanoid glycals

Abstract The reaction of 1,4-anhydro-2-deoxy-5,6- O -isopropylidene- d - arabino -hex-1-enitol ( 1 ) with m -chloroperbenzoic acid in ethanol gives 2,3-unsaturated ethyl glycosides together with saturated ethyl glycosides formed by trans-ring opening of 1,2-epoxide intermediates. Similar results are obtained on peroxidation of 1,4-anhydro-2-deoxy-3- O -(2,3:5,6-di- O -isopropylidene-α- d -mannofuranosyl)-5,6- O -isopropylidene- d - arabino -hex-1-enitol ( 2 ). Products resulting from osmylation of 1 and 2 and cleavage of the osmate esters are also described. 2-Deoxy derivatives are prepared from 1 and 2 by methoxymercuration-demercuration and also by reduction of 2-bromo-2-deoxy derivatives obtained by ethoxybromination.

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.

Reaction of chlorosulphonyl isocyanate with ethyl 4,6-di-O-acetyl-2,3-dideoxy-α-D-erythro-hex-2-enopyranoside: a reinvestigation

The minor products of the reaction of chlorosulphonyl isocyanate with a hex-2-enopyranoside in ether and in acetonitrile include a 3-alkoxycarbonylamino-3-deoxy-allal, 2-(D-glycero-1,2-diacetoxyethyl)furan, two hex-2-enopyranosylamines, and two C–C linked disaccharide derivatives. Reaction mechanisms are discussed.

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.

A method for the preparation of furanoid glycals

The reduction of furanosyl bromides having base-stable protecting groups with sodium in aprotic solvents gives furanoid glycals.

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.