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, 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. 17th communication. Synthesis of ketose-derived nucleosides from 1-deoxy-1-nitroribose

A new approach to ketose-derived nucteosides is described. It is based upon a chain elongation of 1-deoxy-1-nitroaldoses, followed by activation of the nitro group as a leaving group, and introduction of a pyrimidine or purine base. Thus, the nitroaldose 7 was prepared from 3 by pivaloylation (→ 4 ), synthesis of the anomeric nitrones 5/6 , and ozonolysis of 6 (Scheme 1). Partial hydrolysis of 4 yielded 8/9 , which were characterized as the acetates 10/11 and transformed into the nitrones 12/13 . Ozonolysis of 12/13 gave 14/15 , which were acetylated to 16/17 . Henry reaction of 7 lead to 19 and 20 , which were acetylated to 21 and 22 (Scheme 2). Michael addition of 7 to acrylonitrile and to methyl propynoate yielded the anomers 23/24 and 25/26 , respectively. Similar reactions of 16/17 were prevented by a facile β-elimination. Therefore, the nitrodiol 15 was transformed into the orthoesters 27 and then, by Henry reaction, partial hydrolysis, and acetylation, into 28 and 29 (Scheme 2). The structure of 19 was established by X-ray analysis. It was the major product of the kinetically controlled Henry reaction of 7 . Similarly, the β-D-configurated nitroaldoses 23 and 25 were the major products of the Michael addition. This indicates a preferred ‘endo’-attack on the nitronate anion derived from 7 . AMI calculations for this anion indicate a strong pyramidalization at C(1), in agreement with an ‘endo’-attack. Nucleosidation of 21 by 31 afforded 32 and 33 . Yields depended strongly upon the nature and the amount of the promoter and reached 77% for 33 , which was transformed into 34 , 35 , and the known ‘psicouridine’ ( 36 ; Scheme 3). To probe the mechanism, the trityl-protected 30 was nucleosidated yielding 37 , or 37 and 38 , depending upon the amount of FeCl₃. Nucleosidation of the nitroacetate 28 was more difficult, required SnCl₂ as a promoter, and yielded 39 and 40 . The β-D-anomer 40 was transformed into 36 . Nucleosidation of 23 (SnCl₄) yielded the anomers 41 and 42 , which were transformed into 43 and 44 , and hence into 45 and 46 (Scheme 4). Similarly, nucleosidation of 25 yielded 47 and 48 , which were deprotected to 49 and 50 , respectively. The nucleoside 49 was saponified to 51 . Nucleosidation of 21 by 52 (SnCl₂) afforded the adenine nucleosides 53 and 54 (Scheme 5). The adenine nucleoside 53 was deprotected (→ 55 → 56 ) to ‘psicofuranine’ (1), which was also obtained from 58 , formed along with 57 by nucleosidation of 28 . The structure and particularly the conformation of the nitroaldoses, nitroketoses, and nucleosides are examined.     

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. 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 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).     

Acylation of N-acetylneuraminic acid

Summary The direct acylation of N-acetylneuraminic acid takes place ambiguously and leads to two reaction products: the acylated -lactone and the acylated derivative of the pyranose form of the acid.Khimiya Prirodnykh Soedinenii, Vol. 3, No. 2, pp. 191–197, 1967     

Glycosidation of N-acetylneuraminic acid

Conclusions The synthesis of the methyl esters of 9-O-(-D-glucopyranosyl)- and 9-O-(-D-galaetopyranosyl)-N-acetylneuraminic acid is described.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 215–217, January, 1968.     

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 .     

The benzhydryl ester of N-acetylneuraminic acid

Conclusions Benzhydryl protection of the carboxy group of N-acetylneuraminic acid has been described for the first time.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1261–1262, July, 1966.     

Synthesis of 4-o-(N-acetyl-β-D-glucosaminyl)-6-o-acyl-N-acetylmuramyl-L-alanyl-D-isoglutamine

Long-chain acyl derivatives of the disaccharide dipeptide, which is a common building unit of bacterial cell walls, were synthesized in order to test their immunostimulating activity.     

A new synthesis of N-acetylneuraminic acid

A new synthesis of N-acetylneuraminic acid (Neu5Ac; 28 ) via aldehyde 10 is described. The aldehyde 10 was obtained from N, acetyl-D -glucosamine ( 11 ; 5 steps, overall yield ca. 6%) or from D-glucono-1,5-lactone ( 17 ; 6 steps, overll yield ca 57%). Thus, on the one hand, N-acetyl-D -mannosamine ( 12 ), obtained from 11 , was transformed into the known dithioacetal 14 and hence into the (ethylthio)dihydrooxazole 16 , which was cleaved under weakly acidic conditions to the aldehyde 10 . On the other hand, the known ester 18 , obtained from 17 , was sulfonylated and further transformed via the azide 20 into the N-acetyl-D -mannonate 22 . Reduction of 22 to 23 and oxidation of 23 with ‘periodinane’ again gave 10 . The aldehyde 10 was treated with the organozinc reagent 8 obtained from tert-butyl 2-(bromomethyl)acrylate ( 2 ) to yield predominantly 24 , which was transformed (two steps) into the 2-methylidene-D -glycero-nononic acid 27 and hence into Neu5Ac (28).     

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.     

Aspartase-Catalyzed Preparative Scale Synthesis of 15N-Aspartic Acid

A preparative scale synthesis of ¹⁵N-aspartic acid from fumarate and ¹⁵NH₄OH catalyzed by immobilized aspartase has been developed. Immobilization of aspartase in membrane enclosed enzyme immobilization (MEEI) facilitates the separation of the enzyme from product and makes the enzyme stable and durable for multiple usage. A simple isolation procedure in total yield of 62% using perfusion ion exchange chromatography renders the procedure more practical.     

The first synthesis of N-acetylneuraminic acid 1,7-lactone

N-Acetylneuraminic acid is transformed into its until now unavailable and rather unwieldy 1,7-lactone, via the manageable 2-benzyloxycarbonyl N-acetylneuraminic acid 1,7-lactone which generates the free lactone in quantitative yield by hydrogenolysis.     

15-羟基十五烷酸的脂肪酶催化合成环十五内酯

15-羟基十五烷酸的脂肪酶催化合成环十五内酯