Antibiotics, from carbohydrates

N. K. Kochetkov and A. F. Sviridov, Stereocontrolled synthesis of the main aglycons of 14-member macrolide antibiotics from carbohydrates, Mendeleev Khim. Zh., 6 (1991) 389-400. 

Pelyvas, I. F., Madi-Puskas, M., Toth, Z. G., Varga, Z., Hornyak, M., Batta, G., Szlaricskai, F. Synthesis of new pseudo-disaccharide amino glycoside antibiotics from carbohydrates. J. Antibiot. 1995, 48, 683-695. 

Furoic acid (furan-2-carboxylic acid, or pyromucic acid) is used as a bactericide, and the furoate esters are used as flavoring agents, as antibiotic and corticosteroid intermediates. It is obtained by the enzymatic or chemical/catalytic aerobial oxidation of furfural (2-furalaldehyde) the latter is the only unsaturated large-volume organic chemical prepared from carbohydrates today. D-Xylose and L-ara-binose, the pentoses contained in the xylan-rich portion of hemicelluloses from agricultural and forestry wastes, under the conditions used for hydrolysis undergo dehydration to furfural. 

A. F. Sviridov, A. Yu. Romanovich, and O. S. Chizhov, Synthetic studies in polyene macrolide antibiotics. 1. Synthesis of C1-C6 and C7-C12 fragments of amphothericin-B from carbohydrate precursors, Bioorg. Khim., (1987) 1665-1671. 

Sch 47554 (234) and Sch 47555 (235) are two novel antifungal antibiotics from Streptomyces sp. SCC-2136 [167]. They were the first angucyclines containing 3 -deoxyaquayamycin (236) as the aglycon moiety, i.e., these compounds bear a C-glycosidically bound D-amicetose moiety instead of a D-olivose moiety in their aglyca. L-aculose and L-amicetose occur as further carbohydrate moieties. 

The potential of the ester enolate Claisen rearrangement for the stereocontrolled synthesis of highly functionalized, complex systems has been demonstrated in numerous applications in natural product synthesis. Utilizing the 1,3-chirality transfer Ireland has synthesized oxygen heterocycles with chiral side chains, such as are found as units in polyether antibiotics and macrolides, starting from enantiomerically pure furanoid or pyranoid glycal systems of type (41), which are easily accessible from carbohydrates (Scheme 65). ... 

Mitomydn and Rifamycin.—Common to antibiotics like mitomycin C (190) and rifamycin S (193) is a C7N unit (shown in heavy bonding) which, it has been supposed, derives from carbohydrate metabolism. Recent experiments on mitomycin and rifamycin biosynthesis have been directed to discovering more precisely what the intermediates in the generation of this unit are. 

Although the search for new, more active /8-lactam antibiotics, or for new methods of their synthesis does not represent contemporary world research trends, a variety of compoimds having /8-lactam fragments have been foimd to display very interesting, but not antibacterial activities [20]. This prompted us to update the report on the synthesis of /8-lactams from carbohydrates. The present survey comprises fiterature published after 1994. 

The presented review describes total syntheses directed towards 6-amino-6,8-dideoxy-D-eryt/iro-D-galacto-octose, commonly named lincosamine - the sugar component of the antibiotic lincomycin. In the first part we present total syntheses of lincosamine that start from carbohydrate precursors. The D-galactose-derived aldehyde is the most frequently used synthon. In the second part, total syntheses of lincosamine from non-carbohydrate precursors are presented. This part of the review is divided into two subsections. The first one groups syntheses based on the application of furan compounds. In the second one we present a hetero-Diels-Alder approach to the synthesis of lincosamine. 

Goldinonolactone (40) and the chiral tetrahydrofuran (41) were key intermediates in a chiral, but non-carbohydrate-based, synthesis of the antibiotic aurodox both these intermediates are also accessible from carbohydrates, (40) being made from an L—mannose derivative and (41) from D-mannose via a previously described acetyl-... 

A review on the total synthesis of macrolide antibiotics includes discussion of chiral routes to the aglycones from carbohydrates. Hethynolide (27), the aglycone of methymycin, has been prepared from the hydroxy-aldehyde (28) and the acid (29) by esterification followed by intramolecular Wadsworth-Emmons reaction (Scheme 5) ... 

The same chromophore as is found in the arcyriaflavins occurs also in rebeccamycin (516) and in its dechloro derivative, two antitumour antibiotics isolated from Nocardia aerocoligenes 510). Also closely related to these compounds are staurosporin (517), an antibiotic from Streptomyces staurosporeus which exhibits pronounced antihypotensive activity 258), and other carbohydrate bridged bisindoles (575). Due to the small amounts of Arcyria metabolites available from the... 

We have abstracted over 1400 references in carbohydrate chemistry for 1983. The areas of interest reflected in these references have confirmed the trends apparent in recent years. Besides the well-established fields of glycoside, nucleoside, and antibiotic chemistry, there has been a rapid increase in papers reporting the synthesis of chiral natural products from carbohydrate precursors, and a separate chapter on oligosaccharides has clearly justified its inclusion. Incidentally, these last two chapters have both resulted from suggestions made to us by interested readers, and we would like to encourage further participation of this kind. The emphasis in these areas should not obscure the fact that many other aspects of monosaccharide and oligosaccharide chemistry continue to attract much interest, as is demonstrated by the fact that only six of the twenty-four chapters in this volume contain fewer than thirty references. 

A number of papers have described routes from carbohydrates to hydroxyl-ated aminoacids. The azide (78), derived from L-arabinose, was converted, via the 4,5-azirldine. into polyoxamlc acid (79), a constituent of the polyoxin class of antibiotics.The aminosugar derivative (80), an intermediate in Horton s daunosamine synthesis, can be transformed (Scheme 19) into (81), and hence into the lactone (82), which is a protected form of the hydrojqrlated 3-amino-acid found in the antiulcerogenic compound AI-77-B the regiochemistry in the reductive opening of the acetal is unexpected. 72 o-Glucose has been converted... 

A review of synthetic approaches to antibiotics mentions those towards lincosamine from carbohydrate and non-carbohydrate precursors. ... 

The complex sixteen-membered-ring macrolide antibiotic tylosin (191) is extensively used today as a therapeutic agent and a nutrient. The molecule has been at the focus of a number of synthetic investigations. This year, Nicolaou and co-workers have described the elaboration of the three fragments (186), (187), and (188) for the synthesis of 0-mycinosyltylonolide (190) in their appropriate optically active forms, and all three were formed from carbohydrate precursors. Combination between (186) and (187) gave rise to an intermediate which, with (188), was then elaborated to the keto-phosphonate (189). The... 

Lactic Acid B cteri. The lactic acid bacteria are ubiquitous in nature from plant surfaces to gastrointestinal tracts of many animals. These gram-positive facultative anaerobes convert carbohydrates (qv) to lactic acid and are used extensively in the food industry, for example, for the production of yogurt, cheese, sour dough bread, etc. The sour aromatic flavor imparted upon fermentation appears to be a desirable food trait. In addition, certain species produce a variety of antibiotics. 

Oligosaccharides also occur widely as components (via glycosidic bonds) of antibiotics derived from various sources. Figure 7.20 shows the structures of a few representative carbohydrate-containing antibiotics. Some of these antibiotics also show antitumor activity. One of the most important of this type is bleomycin A2, which is used clinically against certain tumors. 

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