Analogs monosaccharide synthesis

Preparation of modified, bacterial polysaccharides having monosaccharide analogs inserted into the polymeric chain is of interest for study of the structure-properties relationship in these biopolymers. Incorporation of chemically prepared, modified, biosynthetic precursors of the polymers in enzymic reactions seems a promising approach for achieving this aim. Such an approach, which may be termed chemical-enzymic synthesis, has now been studied by our group,439-441 using O-specific polysaccharides (10-12) of Salmonella serogroups B and E as an example. 

In an article that collates information not extensively treated before, Z. J. Witczak (West Lafayette) describes the synthesis, chemistry, and preparative applications of monosaccharide thiocyanates and isothiocyanates the thiocyanate anion is an ambident nucleophile of great synthetic versatility in approaches to nucleoside analogs and to thio and deoxy sugars. 

Fructose 1,6-biphosphate aldolase from rabbit muscle in nature reversibly catalyzes the addition of dihydroxyacetone phosphate (DHAP) to D-glyceraldehyde 3-phosphate. The tolerance of this DHAP-dependent enzyme towards various aldehyde acceptors made it a versatile tool in the synthesis of monosaccharides and sugar analogs [188], but also of alkaloids [189] and other natural products. For example, the enzyme-mediated aldol reaction of DHAP and an aldehyde is a key step in the total synthesis of the microbial elicitor (—)-syringolide 2 (Fig. 35a) [190]. 

Enzymes Catalyzing C—C Bond Formation for the Synthesis of Monosaccharide Analogs... 

The dephosphorylation of 5-chloro and 5-bromo-D-xylulose-l-phosphate was carried out by the addition of acid phosphatase. After purification, 5-chloro-D-xylu-lose and 5-bromo-D-xylulose were recovered as pure compounds in 47 and 12% yields, respectively, from DHAP. In this study, we have shown that DHAP generated from glycidol 7 can be used in situ as a donor substrate of FruA in the presence of 2-halo-acetaldehydes 20 as acceptor substrates for the synthesis of 5-halo-D-xylulose 19. Given that DHAP aldolases display a broad specificity towards acceptor substrates, this strategy can be applied generally to the synthesis of various analogs of monosaccharides. 

Most of the methods presented for the de novo synthesis of linear monosaccharides can be used to prepare branched-chain sugars and analogs and some examples are given above and below. The branched-chain aminolactone 222 was prepared by two-carbon chain elongation via addition of 221 to 2,3-0-isopropylidene-L-glyceraldehyde (Scheme 13.69) [126]. 

The avermectin family includes several analogs with different biological activities most are roughly 80 20 mixtures of isomers which are prohibitively difficult to separate. The complete synthesis of avermectin Au has been reported (7). Unmetabolized ivermectin or abamectin, and their monosaccharides and aglycones, are the major residues in meat and agricultural commodities (1). These are generally analyzed by HPLC. 

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