L. C. N. Tucker

Studies related to the synthesis of derivatives of 2,6-diamino-2,3,4,6-tetradeoxy-D-erythro-hexose (purpurosamine C), a component of gentamicin C12

Abstract Reduction of 1,6-anhydro-3,4-dideoxy-β- D - glycero -hex-3-enopyranos-2-ulose (levoglucosenone) with lithium aluminium hydride afforded principally 1,6-anhydro-3,4-dideoxy-β- D - threo -hex-3-enopyranose ( 3 ), which was converted into 3,4-dihydro-2( S )-hydroxymethyl-2 H -pyran ( 8 ) following acid-catalysed methanolysis and reductive rearrangement of the resulting α-glycoside 4 with lithium aluminium hydride. 1,6-Anhydro-3,4-dideoxy-2- O -toluene- p -sulphonyl-β- D - threo -hexopyranose, prepared from 3 , reacted slowly with sodium azide in hot dimethyl sulphoxide to give 1,6-anhydro-2-azido-2,3,4-trideoxy-β- D - erythro -hexopyranose, which was transformed into a mixture of methyl 2-acetamido-6- O -acetyl-2,3,4-trideoxy-α- D - erythro -hexopyranoside ( 10 ) and the corresponding β anomer following acid-catalysed methanolysis, catalytic reduction, and acetylation. Acid treatment of methyl 4,6- O -benzylidene-3-deoxy-α- D - erythro -hexopyranosid-2-ulose yielded the enone 15 , which was readily transformed into methyl 6- O -acetyl-3,4-dideoxy-α- D - glycero -hexopyranosid-2-ulose ( 19 ). Procedures for the conversions of DL - 8 , 10 , and 19 into methyl 2,6-diacetamido-2,3,4,6-tetradeoxy-α- D - erythro -hexopyranoside (methyl N,N′ -di-acetyl-α-purpurosaminide C) have already been described.

An approach to branched-chain amino sugars, particularly derivatives of l-vancosamine (3-amino-2,3,6-trideoxy-3-C-methyl-l-lyxo-hexose) and its d enantiomer, via the cyanohydrin route

Abstract Methyl 4,6- O -benzylidene-2-deoxy-α- d - erythro -hexopyranosid-3-ulose reacted with potassium cyanide under equilibrating conditions to give, initially, methyl 4,6- O -benzylidene-3- C -cyano-2-deoxy-α- d - ribo -hexopyranoside ( 7 ), which, because it reverted slowly to the thermodynamically stable d - arabino isomer, could be crystallised directly from the reaction mixture. The mesylate derived from the kinetic product 7 could be converted by published procedures into methyl 3-acetamido-2,3,6-trideoxy-3- C -methyl-α- d - arabino -hexopyranoside, which was transformed into methyl N -acetyl-α- d -vancosaminide on inversion of the configuration at C-4. A related approach employing methyl 2,6-dideoxy-4- O -methoxymethyl-α- l - erythro -hexopyranosid-3-ulose gave the kinetic cyanohydrin and thence, via the spiro-aziridine 27 , methyl 3-acetamido-2,3,6-trideoxy-3- C -methyl-α- l - arabino -hexopyranoside, a known precursor of methyl N -acetyl-α- l -vancosaminide.

Nucleophilic displacements of methyl 2,3-O-isopropylidene-4-O-toluene-p-sulphonyl-α-d-lyxo- and -β-l-ribo-pyranosides, and deamination of the corresponding 4-amino sugars

Abstract Reinvestigation of the reaction of methyl 2,3- O -isopropylidene-4- O -toluene- p -sulphonyl-α- d -lyxopyranoside ( 4 ) with azide ion has shown that methyl 4-deoxy-2,3- O -isopropylidene-β- l - erythro -pent-4-enopyranoside ( 8 , ∼51.5%) is formed, as well as the azido sugar 7 (∼48.5%) of an S N 2 displacement. The unsaturated sugar 8 was more conveniently prepared by heating the sulphonate 4 with 1,5-diazabicyclo-[5.4.0]undec-5-ene. An azide displacement on methyl 2,3- O -isopropylidene-4- O -toluene- p -sulphonyl-β- l -ribopyranoside ( 12 ) furnished methyl 4-azido-4-deoxy-2,3- O -isopropylidene-α- d -lyxopyranoside ( 13 , ∼66%) and the unsaturated sugar 14 (∼28.5%), which was also prepared by heating the sulphonate with 1,5-diazabicyclo[5.4.0]undec-5-ene. Deamination of methyl 4-amino-4-deoxy-2,3- O -isopropylidene-α- d -lyxopyranoside ( 5 ), prepared by reduction of 13 , with sodium nitrite in 90% acetic acid at ∼0°, yielded methyl 2,3- O -isopropylidene-α- d -lyxopyranoside ( 10a , 26.2%), methyl 2,3- O -isopropylidene-β- l -ribofuranoside ( 21a , 18.4%), and the corresponding acetates 10b (34.5%) and 21b (21.3%). These products are considered to arise by solvolysis of the bicyclic oxonium ion 29 , formed as a consequence of participation by the ring-oxygen atom in the deamination reaction. Similar deamination of methyl 4-amino-4-deoxy-2,3- O -isopropylidene-β- l -ribopyranoside ( 6 ) afforded, exclusively, the products 10a (34.4%) and 10b (65.6%) of inverted configuration. Deamination of methyl 5-amino-5-deoxy-2,3- O -isopropylidene-β- d -ribofuranoside ( 20 ) gave 22ab , but no other products. An alternative synthesis of the amino sugars 5 and 6 is available by conversion of 10a into methyl 2,3- O -isopropylidene-β- l - erythro -pentopyranosid-4-ulose ( 11 ), followed by reduction of the derived oxime 15 with lithium aluminium hydride.

Nucleophilic displacement reactions in carbohydrates. Part XXII. Formation of 1,4-anhydropyranoses from 1-O-acetyl-6-deoxy-2,3-O-isopropylidene-4-O-methylsulphonyl-α-L-manno- and -talo-pyranose with sodium azide

1-O-Acetyl-6-deoxy-2,3-O-isopropylidene-4-O-methylsulphonyl-α-L-mannopyranose (10; R = Ac) and the epimeric L-talopyranose sulphonate (12; R = Ac) yielded 1,4-anhydro-6-deoxy-2,3-O-isopropylidene-β-L-talopyranose (11) and 1,4-anhydro-6-deoxy-2,3-O-isopropylidene-α-L-mannopyranose (13), respectively, on treatment with sodium azide in NN-dimethylformamide at 140°. A mechanism involving initial deacetylation is proposed for these and related reactions.

Nucleophilic displacement reactions in carbohydrates : Part XX. Displacements on alkyl α-l-talopyranoside 4-sulphonate derivatives

Abstract The azide displacement reaction on methyl 6-deoxy-4- O -methanesulphonyl-2,3-di- O -methyl-α- l -talopyranoside ( 6 ) in N,N -dimethylformamide yielded methyl 4,6-dideoxy-2,3-di- O -methyl-α- l - threo -hex-3-enopyranoside (7, ca. 50%), methyl 4,6-dideoxy-2,3-di- O -methyl-β- d - erythro -hex-4-enopyranoside ( 8 , ca. 10%), and methyl 4-azido-4,6-dideoxy-2,3-di- O -methyl-α- l -mannopyranoside ( 9 , ca. 40%). The corresponding azide 14 (20%) and the unsaturated sugars 12 (68%) and 13 (12%) were obtained from a comparable reaction on benzyl 6-deoxy-4- O -methanesulphonyl-2,3-di- O -methyl-α- l -talopyranoside ( 11 ).

Convenient syntheses of L-digitoxose, L-cymarose, and L-ristosamine

Methyl 2,3-O-benzylidene-6-deoxy-4-O-(2-methoxyethoxymethyl)-α-L-mannopyranoside (10) and the 4-O-(methoxymethyl) analogue (11) reacted with butyl-lithium to give the 4-O-substituted methyl 2,6-dideoxy-α-L-erythro- hexopyranosid-3-uloses (12) and (13), respectively. Appropriate transformations on these keto-sugars afforded practical syntheses of 2,6-dideoxy-L-ribo-hexopyranose (L-digitoxose)(15), its 3-O-methyl analogue (17)(L-cymarose), and 3-acetamido-2,3,6-trideoxy-L-ribo-hexose (N-acetyl-L-ristosamine).A slight amendment to one of the sugar residues in published structures of the orthosomycin antibiotics flambamycin and avilamycins is indicated.

The intramolecular cyclization of 3,6-anhydro-D-glucal

In a previous report’, 3,6-anhydro-D-glucal (1) and its conversion into 3,6anhydro-2-deoxy-n-arabino-hexose (4) and 2-(o-glJtcero-1,Zdihydroxymethyl)furan by treatment with dilute hydrochloric acid at room temperature have been described. We now report that the anhydride 1 undergoes complete intramolecular cyciization on storage in dry chloroform to give 1,4:3,6-dianhydro-Z-deoxy-%-n-ffr&Gro-hexopyranose (3) (alternatively designated as 1,5:3,6-dianhydro-2-deoxy-r-o-arabinohexofuranose). Attention was drawn to this reaction in both laboratories when the n.m.r. spectrum of a solution of 3,6-anhydro-D-glucal (1) in deuteriochloroform was observed to change markedly over a period of several hours. This change was presumed to be catalysed by traces of acid in the deuteriochloroform used, and, not unexpectedly, it was effected more efficientIy in dry chloroform containing hydrogen chloride. Chromatography on silica gel gave the major product of the reaction as a hygroscopic, low-melting solid, which was readily purified by sublimation. The product was

Formation of 1,4-anhydropyranoses from 1-O-acetyl-6-deoxy-2,3-O-isopropylidene-4-O-methylsulphonyl-α-L-manno- and talo-pyranose

1-O-Acetyl-6-deoxy-2,3-O-isopropylidene-4-O-methylsulphonyl-α-L-mannopyranose (3) and the epimeric L-talopyranose derivative (4) yield the 1,4-anhydropyranoses (7) and (8), respectively, on treatment with sodium azide in hot NN-dimethylformamide; a possible general mechanism is suggested for these and related reactions.

Syntheses of methyl 2,6-diacetamido-2,3,6-trideoxy-α-d-ribo-hexopyranoside (methyl di-N-acetyl-α-d-tobrosaminide) and methyl 2-acetamido-2,3,6-trideoxy-β-l-lyxo-hexopyranoside

Abstract The title glycosides were synthesised from d -glucose, via the common intermediate methyl 2-acetamido-4-O-benzoyl-6-bromo-2,3,6-trideoxy-α- d -ribo-hexopyranoside.

Synthesis of derivatives of methyl 2,6-dideoxy-4-O-methyl-α-D-ribo-hexopyranoside: on the structure of variose

Methyl 3-O-benzoyl-2,6-dideoxy-4-O-methyl-α-D-ribo-hexopyranoside (10) has been synthesised by an unambiguous route from methyl 4,6-O-benzylidene-2-deoxy-α-D-ribo-hexopyranoside (2). The benzoate (10) differs from benzoylated methyl varioside (obtained by way of methanolysis of the antibiotic variamycin), which is claimed to have the same structure.