Azido derivative neuraminic acid

The sialic acid aldolase-catalyzed condensation of D-mannose 8 and pyruvate led, in an excellent yield, to the synthesis of KDN 9 [33], a natural deaminated neuraminic acid first isolated from rainbow trout eggs [34] and then discovered in other species. The discovery that sialic acid aldolase accepts as substrates D-mannose substituted on the 2-position, even by bulky substituents such as phenyl, azido, or bromine, opened the route to novel unnatural sialic acid derivatives [35-39]. Pentoses also are substrates. N-Substituted neuraminic acids could be prepared either directly from the corresponding Af-substituted mannosamine, such as N-thioacyl derivatives [40], or after reduction and acylation of 5-azido-KDN [41]. Recently, AT-carbobenzyloxy-D-mannosamine was converted, in a good yield, into the N-carbobenzyloxy-neurarninic acid, further used as a precursor of a derivative of castanospermine [42]. 

The 4 9-bis-0- and 4>8,9-tris-0-t-butyldimethyl-silylether derivatives 2J and 8 of the biologically important neuraminic acid represent useful starting points for the synthesis of the new structurally varied nonulosonic acid derivatives 2 9 (figure 3) j5C and 21 (figure 6). Opening of the oxirsne ring of 29 with Hl. j leads to the 8-d.esoxy-8-azido-neuraminic acid derivative which corresponds completely 23. 

Addition of 2,4-dimethylbenzenesulfenyl chloride to the glycal derived from tetra-O-acetyl-neuraminic acid methyl ester, followed by reaction with sodium methylthiolate, furnished the 2-methylthio-3-thiosialic acid derivative 14. Its use as a glycosyl donor is referred to in Chapter 4, and the azido phenylselenation of a furanoid glycal is covered in Chapter 9. 

Neuraminic acid derivatives variously N-acylated have been prepared by reduction-acylation of a 5-azido compound, itself produced from 2-azido-2-deoxy-D-mannose using NeuNAc pyruvate lyase.54... 

A large number of aldoses and derivatives have been tested as substrates for NeuSAc aldolase which adds pyruvic acid to the aldose. A free hydroxyl group is required at C-3 of the aldose, and aldoses with the -configuration at C-3 lead to products with the iS-configuration at C-4 in the product. An enzymic method for the conversion of /V-acetyl-D-mannosamine and D-mannose into neuraminic acid and Kdo respectively has been improved and simplified, and the reactions were carried out on a 10 g scale. iV-Acetyl-4-azido-4-deoxy-D-mannosaniine has been converted with an aldolase into 5-acetamido-7-azido-3,5,7-trideoxy-D-g/ycero-D-gfl/flcro-2-nonulopyranosonicacid. ... 

Anomeric carbodithioates, both O- and N-linked have been investigated. The O-ethyl derivative, i.e. the ethyl S-glycosyl xhantate, of 2-azido-galactopyranoses was found to be an efficient donor activated by either Cu(OTf)2 or DMTST [138, 139], but especially the same type of derivative of N-acetyl-neuraminic add has proven to be an excellent alternative as a sialic acid donor, which has found general applications activated by thiophilic promoters as DMTST or MeSOTf (Scheme 25) [140-142]. 

---