Polyoxin antibiotics

The reaction protocol was further extended to the concise synthesis of poly-oxamic acid, the unique polyhydroxyamino acid side-chain moiety of the antifungal polyoxin antibiotics (63). Treatment of the template 205 under standard thermal cycloaddition conditions with (5)-glyceraldehyde acetonide led to the formation of a single diastereoisomer 208 in 53% yield. Subsequent template removal released polyoxamic acid 209 in essentially quantitative yield. This represents a matched system, with the mismatched system leading to more complex reaction mixtures (Scheme 3.70). 

Polyoxlns. The polyoxin antibiotics are effective against fungi that contain chitin in their cell walls. The resistance to polyoxlns in some fungi of this type appears to be related to a permeability factor rather than to a change in the site of action (14). Polyoxlns competitively inhibit chitin synthetase and thus prevent the incorporation of uridinediphospho-N-acetylglucosamine into the chitin polymer (14). 

Polyoxin antibiotics were discovered in Japan in cultures of Streptomyces cacaoi var. asoensis (Suzuki et al., 1965). They are a mixture of related components with similar physical and chemical properties. The structure of polyoxins (15, 16) was elucidated by Isono et al. (1969). That, for example, of polyoxin B was found to be... 

Chitin is a major component of fungal walls (but also found in insects, etc.). The enzyme that synthesizes chitin (chitin synthase) is a target for the polyoxin antibiotics. 

A transglycosylation reaction involving iV -benzoyl-iV ,9-bis(trimethylsilyl)-adenine and a suitably protected uracil polyoxin C has been used in preparing the adenin-9-yl analogue (615) of the nucleoside skeleton of the polyoxin antibiotics, which contain a labile 5-amino-5-deoxy-p-D-allofuranosyluronic acid residue. ... 

Investigation of the biosynthesis of polyoxin antibiotics from labelled substrates by S. cacaoi has revealed that the 5-amino-5-deoxy-)3-D-allofuranosyl-uronic acid residue of these antibiotics is not derived via oxidation of either D-glucose or o-allose at C-6, but is formed from triose precursors. ... 

The 3, 5-iV-formylepimine derivative (432) [derived from the diacetal (431)] has been converted into a protected analogue (433) of the polyoxin antibiotics. The stereochemistry of the AT-formylepimine derivative (432) was established by A -ray crystallographic analysis. A series of lipophilic 9-(3-alkyl-3-deoxy-j8-D-ribofuranosyl)adenines (434) has been prepared by glycosylation of 6-benzamido-9-chloromercuripurine with the appropriate branched-chain sugar... 

Antifungal antibiotic (+ )-polyoxin J can be obtained in 46,4% yield by combining the derivative of 5-O-carbamoylpolyoxamic acid (348) with thymine polyoxin C (347) (Scheme 2.152) (196, 583)... 

Michael additions to sugar nitro olefins have received considerable less attention than the Henry reaction involving nitro sugars. Early examples of Michael addition include the synthesis54 of licoricidin by Paulsen in 1982, the addition of phosphorous nucleophiles to a D-glucose based nitro olefin55 by Yamashita in 1987 and the synthesis of the natural antibiotic polyoxin published by Barret in 1990.56... 

The discovery of the polyoxin group (1) of antifungal nucleoside antibiotics (2) spurred the attention of synthetic chemists as well as biologists for a number of reasons. Their unusual structural features combined with unique biological activity fostered studies on many fronts (3). During their studies on the biosynthesis of the polyoxins, Isono, Crain and McCloskey (4) discovered three novel acidic nucleosides which they called octosyl acid A, B and C,... 

Fermentation procedures for preparing uridine 5 -(2-acetamido-2-deoxy-a-D-glucopyranosyl pyrophosphate) have also been reported. One of them255 involves the cultivation of Helminthosporium sativum in the presence of 2-amino-2-deoxy-D-glucose and the antibiotic polyoxin the latter is an inhibitor of chitin biosynthesis. The other256 utilized the incubation of yeast cells with uridine 5 -phosphate in the presence of an excess of 2-amino-2-deoxy-D-glucose and inorganic phosphate.257... 

Polyoxins and Neopolyoxms. The polyoxins and neopolyoxins are peptidylpyrimidine nucleoside antibiotics that have achieved use as agricultural fungicides. See Fungicides. 

Polyoxins. The polyoxins, a new group of peptidyl-pyrimidine nucleoside antibiotics, are produced by Streptomyces oaoaoi var. asoensis (32,33). Polyoxins are composed of thirteen components (A - M) of some closely related Mpeptidic nucleosides11 as referred by Isono and Suzuki (34). They can be safely used with no toxicity to man, livestock, fish and plant. Such excellent characteristics may be due to the fact that polyoxins selectively... 

Recently, Nishimura et at. (47) have reported the discovery of polyoxin resistant strains of A. kikuehiana in some orchards of Tottori Prefecture, Japan. Hori et at. (48) suggested that the resistance is caused by a lowered permeability of the antibiotic through the cell membrane into the site of chitin synthesis. 

Difficulty for analysis in micro-scale Antibiotics are generally mixtures of various structurally related components like polyoxins. This complexity is a difficulty for analysis in microscale and safety evaluation of compounds. 

Isono K, Asahi K, Suzuki S (1969) Studies onpolyoxins, antifungal antibiotics. 13. The structure of polyoxins. J Am Chem Soc 91 7490-7505... 

In the synthesis of ( + )-polyoxamic acid36, representing a common structural feature of the polyoxin-type antifungal antibiotics, rearrangement of a trichloroacetimidate 1, derived from L-tartrate, gives a 1 1 mixture of diastereomers 2 and 3, showing no induction by the stereogenic centers outside the electrocyclic arena. 

Purine and pyrimidine analogues of nucleic acid components 84MI5. Pyrimidine antibiotics, polyoxines 79H(13)333. 

The polyoxin mixture was a water extract of the agricultural product obtained from Kaken Kagaku Company. The other antibiotics were originally unknown isolates from the SK F fermentation screen. 

During a recent approach to the synthesis of the antibiotic polyoxins, methyl allene was treated with the N-sulfonyl imine from ethyl glyoxylate at 130°C [89] [Eq. (61)]. However, the desired [2+ 2]-cycloadducts 262 - 264 were obtained in only very small amounts, while imino ene product 261 was the major product, formed in 33% yield. 

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