Structural Transformations of N-Acetylneuraminic Acid, VIII. Synthesis of 7-, 8-, 9-Deoxy- and 4,7-Dideoxyneuraminic Acid

Article abstract of DOI:10.1007/BF00810094

The 7- and 8-Iodnonulosonic acid derivatives 1 and 2 react with tributyltinhydride-AIBN to the 7- and 8-deoxy-N-acetylneuraminic acid derivatives 3a and 4a which after hydrolysis give the 7-deoxy-N-acetylneuraminic acid 3b (5-N-acetamido-3,5,7-trideoxy-β-D-galacto-2-nonulopyranosidonic acid = 7-Deoxy-Neu5Ac) and 8-deoxy-N-acetylneuraminic acid 4b (5-N-acetamido-3,5,8-trideoxy-β-D-galacto-2-nonulopyranosidonic acid = 8-Deoxy-Neu5Ac).The 4,8,9-tris-(t-butyldimethylsilyl)-N-acetylneuraminic acid derivative 5a yields after transformation to the 7-O-acetyl compound 5b and partial removing of the protecting groups the derivative 5c.Further reaction with the Mitsunobu-reagent and methyliodide affords the 9-Iodocompound 6a which turned to the 8-O-acetylderivative 6b.Subsequent reduction by means of tributyltinhydride yields first the 9-deoxyderivative 7a and after hydrolysis the 9-deoxy-N-acetylneuraminic acid 7b (5-N-acetyl amido-3,5,9-trideoxy-D-glycero-β-d-galacto-2-nonulopyranosidonic acid = 9-Deoxy-Neu5Ac).Another synthesis of 7b follows the route 8f -> 8g -> 7c.The Deoxy-N-acetylneuraminic acid 3b could be prepared also by an alternative procedure using the methyl-β-8,9-methylethylen-4-O-t-butyldimethylsilyl-N-acetylneuraminic acid methylester 8a via the intermediate compounds 8d and 8e.Application of the 8,9-O-methylethyliden-N-acetylneuraminic acid derivative 8 opens an approach to the xanthogenates 8a and 8b which could be reduced to the deoxy-N-acetylneuramic acid derivatives 9a and 10a.Hydrolysis of 10a yields the 4,7-dideoxy-N-acetylneuraminic acid 10b (5-N-acetamido-3,4,5,7-tetradeoxy-β-D-lyxo-2-nonulopyranosidonic acid = 4,7-Dideoxy-Neu5Ac). - Keywords: Deoxygenation of sialic acids; Xanthogenates of sialic acids; Reaction of side chain deoxy-iodo sialic acid with tributyltinhydride; Reaction of xanthogenates of sialic acids derivatives with tributyltinhydrde