Neuraminic acid natural derivatives

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 sialic acids are a large family of mono-saccharides derived from 3-deoxy-non-2-ulosonic acid. The three major sialic acids found in nature are W-acetyl (NeuSAc) 1 and A-glycolyl (NeuSGc) 2 derivatives of neuraminic acid (5-amino-3,5-dideoxy-D-gfycero-D-.ga/acto-non-2-ulosonic acid) and KDN (3-deoxy-D- /ycero-D- a/acto-non-2-ulosonic acid) 3 (O Fig. 1)... 

Natural sialic acids (Schauer 1982 1991) are derivatives of 5-amino-3,5-dideoxy- D-glycero-D-galacto-nonu osonic acid 12.1. This awkward name has been replaced by neuraminic acid . The most common derivative is N-acetyl-neuraminic acid 12.2 whose configuration is easy to memorize because, in the Fischer representation, 12.3, it is presented as an aldolic condensation product of N-acetylmannosamine (2-acetamido-2-deoxy-D-mannose) and pyruvic acid. When the expression sialic acid is used without any other precision, it is in reference to derivative 12.2. It exists in the free state or glycosidated in the d-conformation, which allows an equatorial disposition of the three-carbon side chain. Structure 12.2 represents the stable /3-anomer of the free sugar with an axial anomeric hydroxyl group and all-equatorial non-anomeric substituents. An X-ray spectrum of this crystallized /3- anomer confirms this conformation and reveals, moreover, that the side chain has the zig-zag conformation with two... 

Subsequently, a number of other compounds isolated from natural products were related to neuraminic acid by formation, from them, of its mono-methoxy derivative. These included prehemataminic acid from erythrocytes, gynaminic acid from human milk and meconium, lactaminic acid... 

Acylated neuraminic acids and other derivatives of neuraminic acid may also be called sialic acids (abbreviated Sia) when the nature of the (V-acyl substituent(s) is not relevant or is unknown. ... 

Sialic acid is the general name of a family of nine-carbon sugars, which are N- and O-acyl derivatives of neuraminic acid, 5-amino-3,5-dideoxy-D-glycero-D-galacto-2-nomlopyranosic acid such as 5-N-acetylneuraminic acid (NeuSAc, 1) which is the most natural occurring sialic acid [1]. 

The 4,5-unsaturated, 4-deoxy aminohexopyranuronate 104 is the cyclic, tautomeric form of the corresponding 5-acylamido-3,5-dideoxy-glyculosonate (105), a type of compound that exists in Nature. Neuraminic acid (106) may be regarded as being a derivative thereof... 

---