Neuraminic acid azido

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. 

Azido-2-deoxy-2,3-didehydro-neuraminic acid Neu2en5N3 [350]... 

Af-Acetyl-9-azido-9-deoxy-neuraminic acid (methyl a-glycoside)... 

A -Acetyl-4-allylamino-2,3-didehydro-2,4-dideoxy-neuraminic acid 5-N-Acetyl-4-amino-2,3-didehydro-2,4-dideoxy-neuraminic acid 5-(V-Acetyl-4-azido-2,3-didehydro-2,4-dideoxy-neuraminic acid... 

Al-Acetyl-9-.S-(4-azido-2-nitrophenyl)-2,3-didehydro-2,9-dideoxy-9-thio-neuraminic acid 5-At-Acetyl-2-deoxy-2,3-didehydro-4-epi-neuraminic acid (methyl ester) 5-Af-Acetyl-2-deoxy-2,3-didehydro-4-oxo-neuraminic acid 5-Af-Acetyl-2-deoxy-2,3-didehydro-6-thio-neuraminic acid 5-A -Acetyl-2-deoxy-2,3-didehydro-7-epi-neuraminic acid 5-//-Acetyl-2-deoxy-2,3-didehydro-8-epi-neuraminic acid 5-Af-Acetyl-2-deoxy-2,3-didehydro-7,8-diepi-neuraminic acid 5-N-Acetyl-2-deoxy-2,3-didehydro-8,8-dimethoxy-neuraminic acid... 

Methyl 4,5,7,8,9-penta-(9-acetyl-2-azido-2,3-dideoxy-D-gr/Tccro-a- and p-D-g(a/acro-2-nonulo-pyranosonates (83) were formed by treatment of the p acetate with trimethylsilyl azide in the presence of equimolar amounts of SnCU- The poor yields reported are associated with problems in separation of the catalyst. Formation of the neuraminic acid analog, namely methyl (5-acetamido-4,7,8,... 

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. ... 

An improved procedure for the direct synthesis of 1,2-Q-isopropylidene-a-D-glucofuranose has been published treatment of D-glucose monohydrate with acetone in the presence of sulphuric acid gave, after filtration of unreacted starting material and neutralisation with NaOH, a product mixture consisting to 83% of the 1,2-acetonide. The contaminants, mainly a- and -D-glucopyranose, were readily removed by firactional crystallisation. D-Glucose has been converted to the synthetically useful diacetonide dimethyl acetal (1) by exposure to 2,2-dimethoxypropane and sulphuric add in methanol. The transformation of compound (1) to 2-azido-2-deo -D-maimose and hence to neuraminic add is covered in Chapter 16. 

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]. 

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