Acetylneuraminic acid synthesis

DeNinno MP (1991) The synthesis and glycosidation of N-acetylneuraminic acid. Synthesis 1991 583-593... 

An elegant continuous process for N-acetylneuraminic acid synthesis was developed by introducing the N-acetylneuraminic acid-2-epimerase for epimerization of N-acetyl glucosamine 119 and integrating the epimerization with synthesis in an enzyme-membrane reactor [151]. Although this process has an excellent space-time yield, the epimerase enz)une is not freely available and the product stream is very dilute and chromatography is required for purification, making scale-up difficult. 

DeVries, G. H., and Binkley, S. B., 1972, 3-Hydroxy-N-acetylneuraminic acid. Synthesis and inhibitory properties. Arch. Biochem. Biophys. 151 243. 

Thus, an alkene can be considered as a masked ketone that can be unmasked by ozonolysis. This is illustrated by the synthesis of N-acetylneuraminic acid via the ozonolysis of the precursor acrylic acid in THF/aqueous media (Eq. 3.22). The use of aqueous media facilitated the solubility of the polyhydroxyacids.92... 

Vasella has used deoxy-nitro sugars for the synthesis of various biologically important carbohydrates,10 and the radical nitromethylation of deoxy-nitro sugars has been used for synthesis of fructose 6-phosphate11 and 6-C-methyl and 6-C-(hydroxymethyl)analogues of V-acetylneuraminic acid (see Scheme 7.2).12... 

Takahashi and coworkers described an effective sialylation method utilizing the N-Fmoc, N-Troc and N-trichloroacetyl-P-thiophenyl sialosides (Scheme 4.6d) [167]. It was found that the N-Troc derivative of N-acetylneuraminic acid performed better than the corresponding N-Fmoc derivative. An N-Troc P-thiosialoside was applied for the synthesis of glycosyl amino acids by one-pot glycosylation [167]. Importantly, it was found that the N-Troc protecting group could be converted into an acetamido moiety without causing racemization of the peptide. 

Example 5 Hayakawa and Noyori group in their studies on new activators for phosphoroamidite coupling reactions have applied the most effective member of the group of acid/azole complexes AT-(phenyl)imidazolium tri-flate (N-PhIMT) in the efficient synthesis of biologically important compounds [20j]. A noteworthy example is synthesis of cytidine-5 -monophos-pho-AT-acetylneuraminic acid. This compound is a source of sialic acid in the sialyltransferase-catalysed biosynthesis of sialyl oligosaccharides [25]. 

Total Synthesis of the Biologically Active Form of A -Acetylneuraminic Acid... 

N-Acetvlneuraminic Acid Aldolase. A new procedure has also been developed for the synthesis of 9-0-acetyl-N-acetylneuraminic acid using the aldolase catalyzed reaction methodology. This compound is an unusual sialic acid found in a number of tumor cells and influenza virus C glycoproteins (4 ). The aldol acceptor, 6-0-acetyl-D-mannosamine was prepared in 70% isolated yield from isopropenyl acetate and N-acetyl-D-mannosamine catalyzed by protease N from Bacillus subtilis (from Amano). The 6-0-acetyl hexose was previously prepared by a complicated chemical procedure (42.) The target molecule was obtained in 90% yield via the condensation of the 6-0-acetyl sugar and pyruvate catalyzed by NANA aldolase (Figure 6). With similar procedures applied to KDO, 2-deoxy-NANA and 2-deoxy-2-fluoro-NANA were prepared from NANA. 

Figure 6. Synthesis of 9-0-acetyl-N-acetylneuraminic acid. The aldol acceptor was prepared from N-acetylmannosamine and isopropenyl acetate in DMF catalyzed by protease N obtained from Amano. The aldol condensation was carried out by using N-acetylneuraminic acid aldolase as catalyst.

E. Schreiner, R. Christian, and E. Zribal, Synthesis of 9-deoxy-, 7,9-dideoxy-, and 4,7,9-trideoxy-iV-acetylneuraminic acid and their behaviour towards CMP-sialate synthase, Liebigs Ann. Chem. p. 93 (1990). 

The Sowden homologation [21], based on the nitroaldol condensation (Henry reaction) [22] between the aldehydo sugar and nitromethane in basic medium, followed by the Nef decomposition [23] of the resultant nitronate in strongly acidic conditions, has been employed in a more limited number of cases than the cyanohydrin synthesis. A recent example in this area is shown by the stepwise homologation of (V-acetyl-D-mannosamine (11) into /V-acetylneuraminic acid (12) [24] (Scheme 4). Also, this procedure has found... 

Having set up a protocol for the aminohomologation of various aldehydo sugars, the value of the method was tested by the synthesis of simple natural products. The firsl example involved [57a] the conversion of 2,3 4,5-di-0-isopropylidene-D-arabinose 59 (Scheme 18) through the nitrone 60 into the W-acetyl-D-mannosamine diacetonide 61 and the deprotected compound 11, both well-known key intermediates for the synthesis of /V-acetylneuraminic acid (Neu5Ac) [59,60]. Unfortunately, in this case the addition of 2-LTT (25b) to the nitrone 60 occurred with modest selectivity (ds 75% to the best) therefore, the overall yield of 61 was quite low (29%). 

L. Benzing-Nguyen and M. B. Perry, Stepwise synthesis of /V-acetylneuraminic acid and /V-acety 1 - K ncuraminic acid, J. Org. Chem. 73 551 (1978). 

R. Csuk, M. Hugener, and A. Vasella, A new synthesis of /V-acetylneuraminic acid, Helv. Chim. Acta 71 609 (1988). 

T. Kondo, H. Abe, and T. Goto, Efficient synthesis of 2a-glycoside of W-acetylneuraminic acid via phenylsulfenyl chloride adduct of 2-deoxy-2,3-dehydro-lV-acetylneuraminic acid methyl esier tetra-O-acetate, Chem. Lett., p. 1657 (1988). 

A. Hasegawa, J. Nakamura, and M. Kiso, Synthesis of alkyl ot-glycosides of 2-thio-W-acetylneuraminic acid, J. Carbohydr. Chem. 5 11 (1986). 

T. Murase, H. Ishida, M. Kiso, and A. Hasegawa, A facile regio- and stereoselective synthesis of a-glycosides of W-acetylneuraminic acid, Carbohydr. Res. 184 Cl (1988). 

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