Iduronic acid synthesis

For the synthesis of D-glucuronic acid, methods of oxidation of suitable D-glucose derivatives have been devised during the past two decades these procedures have been comprehensively reviewed by Marsh,6 Mehltretter,7 and Heyns and Paulsen.8 For special purposes, for example, for the preparation of 6-I4C-labelled D-glucuronic acid, chain-extension reactions of 1,2-O-isopropylidene-a-D-xy/o-pen-todialdo-I,4-fiiranose by the cyanohydrin synthesis9 or by ethynyla-tion10 are used, but these frequently yield mixtures of D-glucuronic acid and L-iduronic acid. 

L-lduronic acid synthesis Synthesis of L-iduronic acid residues occurs after D-glucuronic acid has been incorporated into the carbohydrate chain. Uronosyl 5-epimerase causes epimerization of the D- to the L-sugar. 

These reactions were applied to the synthesis of phenol derivatives [32], aminoglycoside antibiotics [33] etc.. . and are of great interest in other synthetic applications, b) In the field of substitution reactions, a more recent application of photobromination reactions is described for the synthesis of L-iduronic acid derivatives from D-glu-curonic acid analogs 26. The C-5 photobrominated product 27 is reduced with tri-n-butyltin hydride to give a mixture of starting material and the L-idopyranuronate 28 by a supposed rapidly interconverting radical [29] (Scheme 14). 

N. Baggett and A. Smithson, Synthesis of L-iduronic acid derivatives by epimerisation of anancomeric D-glucuronic acid analogues, Carbohydr. Res., 108 (1982) 59-70. 

Nowadays, no saturated or unsaturated mannuronic acid derivatives are commercially available in a monomeric form, thereby limiting their uses in chemical synthesis. In contrast to o-glucuronic, o-galacturonic, or L-iduronic acids, only the D-mannurone lactone form (D-mannofuranurono-6,3-lactone) was available for... 

The L-iduronic acid-like 1-iV-imino sugars 39-41 have been prepared from a siastatin B derivative (See Vol. 27, p. 237, ref. 96) as metastasis inhibitors. The synthesis and glycosidase activity of other siastatin B analogues are mentioned in Chapter 19. 

Iduronic acid is not handled as the monomer in any known pathway of polysaccharide synthesis. It arises after polymerisation. Though sugar nucleotide derivatives of it have been described, their function, if any, is unknown. 

The synthesis of derivatives of L-iduronic acid from 1,2-0-isopropylidene-a-D-xy/o-pentodialdo- 1,4-furanose by way of an acetylenic intermediate is mentioned in Chapter 12 (see Scheme 58). A related sequence of reactions with methyl 2,3-0-isopropylidene-P-D-nho-pentodialdo-l,4-furanoside has furnished methyl (methyl 2,3-0-isopropylidene-a-L-talofuranosid)uronate and its P-D-a//o analogue from acetylenic precursors. Malonic acid reacted with methyl 2,3-0-isopropylidene-P-D-riho-pentodialdo-l,4-furanoside to give the unsaturated uronic acid derivative (420). 

Moreover, the synthesis of hexasaccharides 52-53 and oclasaccharide 41, partly O-desuIfonated at positions 2 and/or 6 of glucosamine as well as position 2 of iduronic acid have been reported (Figures 7.2 and 7.4) [32, 45, 52]. 

---