The Chemical Synthesis of D-Glucuronic Acid

Mehltretter, C. L., The Chemical Synthesis of D-Glucuronic Acid, VIII, 231-249... 

In the present chapter, the more significant methods which have been reported for the chemical synthesis of D-glucuronic acid will be described and discussed. They are reductive and oxidative procedures and will be... 

Until recent years, the sole somce of /3-D-glucopyranosiduronic acids, and indeed of D-glucuronic acid itself, was the urine of animals fed with the appropriate aglycons, and in most instances the chemical synthesis in the laboratory has yet to be achieved. In some cases [for example, phenol-phthalein (mono-)j3-D-glucopyranosiduronic acid], laboratory synthesis still presents difficulties. 

Compounds known to behave in this way in vivo are listed in recent reviews in this Series.1 2 The structures of some of the /3-D-glucopyranosiduronic acids isolated from urine have been proved by chemical synthesis.3 A few similar derivatives of flavones and triterpenes have been isolated from plants. D-Glucuronic acid also occurs in mammalian tissues as a constituent of acid mucopolysaccharides (aminodeoxypolysaccharides, containing uronic acid), such as hyaluronic acid, chondroitinsulfate, and heparin,4 and it is a direct precursor of L-ascorbic acid in plants and mammals.6 It is present in many of the plant polysaccharides classified as hemicelluloses6 and gums,7 and it has also been found in certain bacterial polysaccharides.4... 

While this approach afforded gram quantities of a heparin-like polysaccharide with anticoagulant activity, unnatural saccharide units, such as 3-0-sulfo-D-glucuronic acid, were present in their product, suggesting a limitation in the selectivity of chemical sulfonation/desulfonation in HS synthesis. 

Whitesides and coworkers have carried out a comparison of enzymic and chemical routes to CTP, GTP and UTP on a 10-gram scale. They concluded that CTP and GTP were best made enzymically, and UTP by reaction of CTP with nitrous acid. The triphosphates were then employed for the enzymic synthesis of UDP-Glucose, UDP-Glucuronic acid, and GDP-Mannose.i94 Cytidine diphosphate sugars have been prepared from the 3,6-dideoxyhexoses paratose and abequose,193 and all four nucleoside diphosphate sugars of 6-sulpho-a-D-quinovose have been synthesized for studies of sulpholipid biosynthesis in chloroplasts.196 The stable analogue (138) of CMP-KDO has been prepared by a triester approach, but was only a weak inhibitor of KDO incorporation into lipopolysaccharides.197 A reference to acetylated forms of UDPGlc is mentioned in Chapter 7. 

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