Deoxy-nitrosugars, 7th communication Synthesis of methyl shikimate and of diethyl phosphashikimate from D-ribose

The chain elongation of the deoxy-nitroribose 6 by a Michael addition to the vinyl-phosphonate 7 followed by a solvolysis gave the heptulosephosphonate 11 (87%). From 11 , the key intermediates 15 and 16 (77%) were obtained by a highly diastereoselective reduction, followed by detritylation, periodate cleavage, and silylation. Methoxycarbonylation of 15 and 16 gave 17 and 18 which were converted into methyl shikimate ( 21 ; 79%) by intramolecular olefination and partial deprotection. Similarly, phosphonoylation of 16 gave 22 (99%) which was transformed into the diethyl phosphashikimate 2 (53% from 6).     

Deoxy-nitrosugars 8th communication Convenient preparation of 1-C-nitroglycosyl chlorides. Halonitro ethers from hydroxy oximes

Partially protected 4- or 5-hydroxy-sugar oximes were transformed into 5- or 6-membered 1-C-nitroglycosyl chlorides, respectively, by reaction with NaOCl under phase-transfer conditions. With the exception of the oxidation of the gluco-derivative 1 giving the anomers 6 and 7 , the reactions were completely diastereoselective.     

Deoxy-nitrosugars 15th communication Synthesis of N-acetylneuraminic acid and N-acetyl-4-epineuraminic Acid

A synthesis of N-acetylneuraminic acid ( 1 ) and of N-acetyl-4-epineuraminic acid ( 2 , R = H) from 2-acetamido-4,6-O-benzylidene-1,2-dideoxy-1-nitro-D -mannopyranose ( 3 ) and 2-acetamido-1,2-dideoxy-4,6-O-isopropylidene-1-nitro-D -mannopyranose ( 4 ), respectively, is described. Michael addition of 3 and 4 to tert-butyl 2-(bromomethyl)prop-2-enoate ( 5 ) and subsequent hydrolytic removal of the NO₂ group gave the 4-nonulosonate tautomers 6 / 7 and 8 / 9 , respectively (Scheme). Stereoselective reduction of 6 / 7 and 8 / 9 with NaBH₄/AcOH in dioxane/H₂O yielded 12/13 (94:6) and 14/15 (92:8), respectively. Reduction of 6 / 7 and 8 / 9 in the absence of AcOH or in EtOH gave 12 / 13 (15:85) and 14 / 15 (15:85), respectively. Ozonolysis of 12 and 13 followed by hydrolysis gave tert-butyl neuraminate 22 and tert-butyl 4-epineuraminate 24 , respectively. Ozonolysis of 14 / 15 , separation of the products 20 and 21 , and hydrolytic removal of the isopropylidene groups gave 22 and 24 , respectively. The tert-butyl ester 22 was saponified to give 1 , which was further characterized as the methyl ester 23 . Saponification of 24 gave the crude 4-epimer of 1 , which was converted into the stable Na salt 2 and also into the methyl ester 25 .     

Deoxy-nitrosugars. 10th Communication. Synthesis of Isosteric Phosphonate Analogues of Ulose-1-Phosphates

A general approach to isosteric phosphonate analogues of ulose-l-phosphates is described. A base-catalysed chain elongation via a Michael addition of 1-deoxy-1-nitro-sugars 4, 8 , and 16 to the vinylphosphonate 18 followed by hydrolysis of the nitro adducts gave the analogues of D -ribulose-1-phosphate, D -fructose-1-phosphate, and D -sedoheptulose-1,7-diphosphate 21, 23 , and 27 , respectively, in high yields.     

Deoxy-nitrosugars. 16th Communication. Synthesis of N-acetyl-4-deoxyneuraminic acid

The synthesis of 5-acetamido-4-deoxyneuraminic acid ( 1 ) is described. Acetylation of a mixture of the epimeric triols 4 and 5 gave the tetraacetates 7 and 8 (Scheme 1). Ozonolysis of a mixture of these acetates followed by base-promoted β-elimination led to the (E) -configurated α,β-unsaturated keto ester 10 , which was hydrogenated to give the saturated keto ester 11 . Saponification of 11 and hydrolytic removal of the benzylidene group followed by anion-exchange chromatography gave the 5-acetamido-4-deoxyneuraminic acid ( 1 , Scheme 1 and 2). De-O-acetylation (NaOMe/MeOH) of the keto ester 11 gave a mixture of the tert-butyl ester 12 and the methyl ester 13 , which were converted to tert-butyl N-acetyl-4-deoxyneuraminate ( 14 ) and to methyl N-acetyl-4-deoxyneuraminate ( 15 ), respectively. Hydrogenolysis of the benzylidene acetal 11 followed by de-O-acetylation gave the pentahydroxy ester 16 .     

Deoxy-nitrosugars. 9th communication. Chain elongation of 1-C -nitroglycosyl halides by substitution with some weakly basic carbanions

The 1-C-nitroglycosyl chloride reacted with the anions form 2-nitropropane, nitromethane, and diethyl malonate, to give the chain-extended products 2 (81%), 5 (72%), and 6 (83%), respectively. Treatment of the 1-C -nitroglycosyl bromide 7 by the lithium salt obtained form 8 gave the dodecodiulose derivative 9 (76%). Th β-D-configuration of 2 and 9 was inferred form their NMR and CD spectra. Treatment of 2 and 9 with sodium sulfide gave the enol ethers 3 (96%) and 10 (92%), respectively. The (Z)-configuration of 10 was deduced form the configuration of its hydrogenation product 11 .     

Deoxy-nitrosugars 12th communication Synthesis of isosteric mono-phosphonate analogues of β-and α-D-fructose 2,6-bisphosphate

A synthesis of the isosteric mono-phosphonate analogues 2a and 19 of the β-and α-D -fructose 2,6-bisphosphate, respectively, is described. Chain elongation of the 1-deoxy-1-nitro-D -arabinose 3 (Scheme 1) by a Henry reaction with paraformaldehyde followed by protection of the resulting alcohol (methoxymethyl ether) and a radical-chain substitution by nitromethane anion gave the key intermediates, the gluco-anhydroalditol 6 and the manno-anhydroalditol 7 . These products equilibrated under basic conditions. Conversion of 7 to the aldehyde 9 , Abramov reaction of 9 with diphenyl phosphite followed by deoxygenation according to Barton gave the phosphonate 11 (Scheme 2). Selective hydrogenolysis of 11 , phosphorylation and deprotection gave 2 which was converted to the tetrasodium salt 2a . Similarly, 6 was transformed into the isosteric phosphonate analogue 19 of the α-D -fructose 2,6-bisphosphate (Scheme 3).     

Deoxy-nitrosugars. 5th Communication. The anomeric effect of the nitro group

The 1-deoxy-1-nitro-D -manno-pyranose 4 was transformed into the nitroolefin 5 and hence into the anomeric 1,2-dideoxy-1-nitro-3, 4, 6-tri-O-benzyl-D -arabino-hexopyranoses ( 3a and 3b ; cf. the Scheme). Conformational analysis of 1-benzyloxy-2-nitroethane ( 6 ) by ¹H-NMR spectroscopy (Fig. 2) showed the synclinal conformation to be more stable than the antiperiplanar one by about 1.4 kcal/mol (attractive gauche-effect). This gauche-effect favours the 1-deoxy-1-nitro-2, 3, 4, 6-tetra-O-benzyl-β-D -manno-hexopyranose ( 1b ) possessing an equatorial nitro group, which is, however, qualitatively the less stable anomer. The relative concentrations of the anomers of 1 and 3 , respectively, were determined by ¹H-NMR spectroscopy after base catalyzed equilibration at 37° in CHCl₃-solution (Table). Anomeric effects for the nitro group of approximately 2.4 kcal/mol in 3 and of approximately 3.4 kcal/mol in 1 were calculated.     

Synthesis of 13,14-Dehydro-15-deoxy-16-hydroxy-16-methyl-17-phenoxyprostaglandin B1 Ethyl Ester

Russian Journal of Organic Chemistry - A new synthetic route has been developed for the construction of the main skeleton of ω-aryloxyprostaglandin (PG) via 1,2-addition of lithiated...     

Deoxy-nitrosugars. 6th communication. Stereoelectronic control in the reductive denitration of tertiary nitro ethers. A synthesis of ‘C-glycosides’

The separate, radical denitration with Bu₃SnH of the pyranose derivatives 3, 4, 9 , and 10 gave in good yields exclusively the ‘C-glycosides’ 5 and 11 , respectively (Scheme 1). Similar reduction of the cyclohexyl derivatives 15, 16, 19 and 20 gave 4:1 mixtures of 17, 18, 21 and 22 , respectively, always with predominant formation of an axial C,H-bond. In the furanose series a divergent behaviour was observed for the D -mannose-derived nitro ethers 25 and 27 and the D -ribose-derived nitro ethers 30 and 31 , respectively, in that the former two gave isomerically homogeneous reduction products ( 26 and 28 , respectively; Scheme 3) and the latter a 1:1 mixture of the diastereoisomers 32 and 33 (Scheme 4). The stereochemical results were explained on the basis of the stereoelectronic effect of the ring O-atom, the preferred conformation of the intermediate, pyramidal alkoxyalkyl radicals and steric effects in the trioxabicyclo [3.3.0]octane ring system.     

Analogs of pyrimidine nucleosides. 17. Synthesis of 1-[5(2)-fluoromethyltetrahydro-2-furyl]uracils

The synthesis of 2-fluoromethyltetrahydrofuran is described, and it is shown that chlorination of the latter gives 2-chloro-5- and 2-chloro-2-fluoromethyltetrahydrofurans in a ratio of 5:1. 2,4-Bis(trimethylsilyl) derivatives of uracil were alkylated by means of the mixture of -chloro ethers without separation, and a mixture of the cis and trans isomers of 1-(5-fluoromethyltetrahydro-2-furyl)uracils and 1-(2-fluoromethyltetrahydro-2-furyl)uracils were obtained. The reaction products were identified on the basis of the PMR spectra.See [1] for communication 16.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 256–259, February, 1982.     

Deoxy-nitrosugars. 11th Communication. Reactions of 1-C-nitroglycosyl halides and 1-C-nitroglycosyl sulfones with dialkyl-phosphite anions: Nucleophilic attack vs. single-electron transfer

Treatment of the chloro-nitro-ribofuranose 7 with KPO(OMe)₂ gave the O-amino phosphate 8 (5 %) and the nitrile 9 (62 %). Compound 9 was also obtained by the reaction of 8 with KPO(OMe)₂, and its structure was established by X-ray analysis. Treatment of the chloro-nitro-mannofuranose 10 , the bromo-nitro-ribofuranose 14 , or the bromo-nitro-mannofuranose 16 , respectively, with the K or Na salt of HPO(OMe)₂ lead also to O-amino phosphates and nitriles. The (1-C-nitroglycosyl)phosphonate 22 was obtained (21 %) together with the nitrile 21 (51 %) from the chloro-nitro-mannofuranose 10 and KPO(OEt)₂. The reaction of the 1-C-nitroglycosyl sulfone 25 (NO₂-group endo) with KPO(OEt)₂ gave the (1-C-nitroglycosyl)phosphonate 22 (61%) and the nitrile 21 (11 %), whilst the anomeric sulfone 26 (NO₂-group exo) gave 22 (15 %) and 21 (58 %). In the presence of [18] crown-6, a mixture of the anomers 25 and 26 gave the (1-C-nitroglycosyl)phosphonate 22 in 67 % yield together with 21 (13 %). These findings are rationalized as the result of a competition between a nucleophilic attack of the dialkyl-phosphite anions on the NO₂-group leading ultimately to the nitrile 21 and a single-electron transfer reaction leading to the (1-C-nitroglycosyl)phosphonate 22 .     

Synthesis of (1-->4)-linked 2-deoxy-2-fluoroglucose oligomers. 1

[reaction: see text] Thioglycosides of natural monosaccharides are readily converted into their corresponding chlorides by diphenylchlorosulfonium chloride. This reagent can likewise effect the conversion of the more stable 4-chlorophenylthio 2-deoxy-2-fluoroglucose derivatives into chloride glycosyl donors. On the basis of this activation strategy, it was possible to assemble unnatural oligosaccharides composed of 2-fluorodeoxy sugars.