Regioselective aectylations of sialic acid α‐ketosides

Abstract

Various partially acetylated sialic acid a-ketosides were obtained without expensive protecting group techniques by using trimethyl orthoacetate or dimethylacetamide dimethyl acetal as acetylating agents or by performing a partial Zemplen de-O-acetylation. Using trimethyl orthoacetate as acetylating agent, we synthesized 9-O-acetylated, 8-O-acetylated, and 8,9-di-O-acetylated sialic acid a-ketoside benzyl ester derivatives. The acetylation with dimethylacetamide dimethy1 acetal yielded 9-O-acetylated, 8-O-acetylated, 4,9-di-0-acetylated, 8,9-di-O-acetylated, and 4,8,9-tri-O-acetylated sialic acid a-ketoside benzyl ester derivatives. The partial Zemplen de-O-acetylation permitted the synthesis of 7,8,9-tri-O-acetylated sialic acid a-ketoside benzyl ester derivatives. After catalytic hydrogenation the 8-O-acetylated derivatives 2e and 3d were not stable and were completely converted into the 9-O-acetylated sialic acid a-thioketoside 2k. The N-acetyl-8,9-di-O-acetylneuraminic acid a-aminophenylthioketoside 21 showed a migration of the acetyl group from position 8 to position 7 in polar solvents, yielding a mixture of the 8,9-di-0-and the 7,9-di-O-acetylated derivatives 21 and 2 m in a molar ratio of approximately 1:l. The 7,9-di-O-acetylated derivative 2 m could be separated and was completely stable in methanol. Using the isopropylidene protecting group we could also prepare the 4-O-acetylated sialic acid a-thioketoside 20. Treatment of the 9-O-acetylated derivative 2k with fluorescein isothiocyanate gave the fluorescent derivative 5 .Sialic acids are, as constituents of sialoglycoproteins and gangliosides, widely distributed in the In addition to N-acetylneuraminic acid, a great number of substituted neuraminic acid derivatives occur bearing e.g. acetyl groups at the hydroxyl The acetyl ester groups can be located in the positions 4, 7, 8, or 9 in various combinations. These glycoconjugates containing O-acetylated sialic acids are involved in many biological functions [4]. Especially the O-acetylation is responsible for different biological processes. An acetyl ester group in position 4 blocks the action of bacterial sialidases completely [5]. Acetylation in the glycerol side chain diminishes the sialidase actionL6] and influences in this way the sialic acid catabolism.There are few synthetic methods for obtaining selectively acetylated sialic acid derivatives. First, Haverkamp et al. realized the synthesis of 9-O-acetylated, 4,9-di-O-acetylated and 4,8,9-tri-O-acetylated sialic acid derivatives by using Nacetylimidazole as acetylating agentr71. The selective 9-0-acetylation with trimethyl orthoacetate was described by Ogura et al. [8,91. Also Hasegawa et a1.[l01 synthesized successfully 9-0-and 4,9-di-O-acetylated sialic acid derivatives by use of acetyl chloride/pyridine at -40°C. Recently, a further selective 9-O-acetylation method using dimethylacetamide dimethyl acetal was described byIn addition, Ogura, Hasegawa and coworkers synthesized 4-O-acetylated, 7-O-acetylated, 7,8-di-O-acetylated, 7,9-di-O-acetylate...

Chemistry, biochemistry and biology of sialic acids

“…l), and is abbreviated as Kdn (2-keto-3-deoxynononic acid; also in this case the D-notation is part of the trivial name). Also starting from a-Neu5,8,9Ac3 4-aminophenylthio-glycoside a 1 : 1 equilibrium between the 8,9-and 7,9-di-O-acetylated derivatives is established [57]. Neu5Ac has a pK, value found in the range of 2.2-3.0 in various studies with an average of 2.6.…”

Facile synthesis of oligoyne amphiphiles and their rotaxanes

“…7,8 We first investigated the complete deprotection of the tetra- O -acetyl β- d -glucosyl hexayne TAG6 , that is, the deacetylation of the glucosyl head group by treatment with substoichiometric amounts of NaOMe in methanol according to Zemplén, 55 and the simultaneous or subsequent desilylation with cesium fluoride (Scheme 3). Solutions of the desilylated compound Glu6-H , however, quickly turned dark brown, indicating the fast degradation of the hexayne moieties.…”

New Optically Active 4‐Alkoxyprolinol Ethers Derived from trans‐4‐Hydroxy‐L‐proline

“…[16] Zemplén transesterification with catalytic amounts of sodium methoxide in methanol regenerated the trans-N-acetyl-4-hydroxyprolinol (8) pure enough for ether synthesis. [17] Double O-methylation was carried out with an excess of methyl iodide in the presence of sodium hydride in 61 % yield (from 7). [18,19] The final removal of the amide protecting group upon treatment with 3 n aqueous HCl gave the trans-4-hydroxyprolinol dimethyl ether 1 (hydrochloride) in 96 % yield.…”