The Synthesis of Antibiotic Sugars

Abstract

The term antibiotic sugar denotes the carbohydrate component of an antibiotic. Two alternative approaches are adopted for the synthesis of these neutral and amino sugars, many of which have unusual structures : One route starts from fairly simple non-carbohydrate precursors, the other depending upon the modification of a carbohydrate precursor.

Nucleotide Deoxysugars: Essential Tools for the Glycosylation Engineering of Novel Bioactive Compounds

“…In this respect, new opportunities for the (chemo)enzymatic synthesis of dTDP-deoxyhexoses have been brought about by the cloning of deoxysugar pathway genes. Their successful heterologous expression should therefore facilitate the characterization of the underlying enzymes leading to the synthesis of dTDP-deoxyhexoses as substrates of glycosyltransferases by combinatorial biocatalysis where deoxysugar pathways are reconstituted or combined as OH dTDP-α-D-olivose (1) dTDP-β-L-olivose (2) dTDP-β-L-rhodinose (9) dTDP-β-L-daunosamine (8) dTDP-β-L-mycarose (5) dTDP-α-D-mycaminose (4) dTDP−α-D-desosamine (6) dTDP-α-D-mycarose (3) dTDP-6-deoxy-α-D-allose (7) Fig. (2).…”

“…D-and L-deoxyhexoses are important carbohydrate components which mediate important biological functions of glycoconjugates in animals, plants, and microorganisms [1][2][3][4]. The presentation of deoxysugars is a widely used method of nature to change surface properties of compounds and organisms by influencing the interaction with the environment in a mostly hydrophilic setting.…”

The chemistry of hexenuloses

“…Compound 68 is then R = OBz; R' = CH,; 6 h, 53% R = OH; R' = C,H,; 5 h, 82% R = H; R' = C,H,; 60 h, 85% Some variations to this synthetic route were reported by a number of workers: (1) electrolytic methoxylation of the furylcarbin01,~~~~~ (2) oxidation of furylcarbinol with p e r a~i d s , l~~J~ (3) cleavage of the acetal bonds in 66 with organic per acid^^^*^^ or Dowex 50 resin,@ followed by formic or trifluoroacetic acid in methanol to give 63, and (4) methylation of 68 with methyl iodide in the presence of silver oxide.143J44 The furylcarbinol Bognar and H e r c~e g h l~~J~ described an analogous procedure for the synthesis of hex-3-enopyranosides 76 starting with 5-methyl-2-furaldehyde (72) (Scheme IX). This method is the reversal of the well-known transformation of sugars into furan compounds.…”

“…The attractive features of the methods employed for synthesizing the hexenopyranosuloses are (1) the simplicity and ease of execution of the reactions, (2) the high yields of important intermediates and final products, (3) the low cost and availability of the reagents, and (4) the limited use of chromatographic techniques. The deployment of protecting groups coupled with the availability of modern chemical reagents has simplified efforts in preparing suitably substituted derivatives for use as intermediates in synthetic sequences leading to carbohydrate enones.…”

“…Structural features in hex-or pent-2-enopyranosid-4-uloses make them attractive dienophiles in Diels-Alder reactions: (1) the cis olefinic function will lead to a series of cis adducts; (2) there are present two readily distinguishable one and two carbon fragments;…”