Polyoxin antifungal

The octosyl acids are isolated from Streptomyces cacaoi they are part of a broader group of polyoxin antifungal nucleosides [349]. Danishefsky and co-workers [350] have reported a total synthesis of octosyl acid A featuring the hetero-Diels-Alder addition of ( )-l-methoxy-3-(trimethylsilyloxy)butadiene to a protected D-ribose-derived aldehyde. 

Isono K, Asahi K, Suzuki S (1969) Studies on Polyoxins, Antifungal Antibiotics. 13. Stractiue of Polyoxins. J Am Chem Soc 91 7490... 

Isono K, Asahi K, Suzuki S. Polyoxins, antifungal antibiotics. XIII. Structure of polyoxins. J. Am. Chem. Soc. 1969 91 7490-7505. 

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)... 

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,... 

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). 

An application of the deracemization strategy has provided efficient entry to a novel amino acid substituent of the antifungal agents, polyoxins and nikkomycins, as shown in Scheme 8E.20. The versatile five-carbon building block was obtained from phthalimidation of the hydroxymethyl-substituted epoxide in 87% yield and 82% ee. Straightforward synthesis of polyoxamic acid was then accomplished by subsequent dihydroxylation and selective oxidation of the alkylation product. 

The NCA 138 represents the amino-protected and carboxy-activated form of poly-oxamic acid 140, the hydroxylic amino acid portion of the antifungal family of polyoxins 139, Fig. 8. Other polyolic NCAs such as 141,142, and 143, Fig. 9, have also been prepared from the corresponding a-hydroxy p-lactams with equal success [123, 124]. 

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. 

Polyoxins constitute a group of antifungal metabolites produced by Streptomyces cacaoi var. asoensis, the gross structure of which is divisible into a nucleoside moiety and a dipeptide comprised of a unique functionalized polyhydroxynorvaline known commonly as 5-(9- or d-... 

A group of aminoacylamino- nucleoside antibiotics (more than 25 components) from cultures of Streptomyces tendae, see also polyoxins. The N. exhibit acar-icidal, insecticidal, and antifungal activities. The activity is based on an inhibition of chitin biosynthesis as a result of the structural analogy to UDP-Al-acetyl-... 

Nucleoside antibiotics with a bicyclic carbohydrate unit from Streptomyces cacaoi var. asoensis. Distinctions are made between O. A (pK i 3.0 pKj2 4.3 pKg3 9.4), O. B, and O. C(pK, 3.1 pK 24.5 pK,j 9.9). 0. represent a large group of polyoxin-like antibiotics with antifungal activities. 

C15H23N7O5, Mr 381.39, amorphous, LD50 (mouse p. o.) 1000 mg/kg. An antiviral and antifungal nucleoside antibiotic from cultures of Streptomyces griseolus and S. incamatus. The development of S. as a fungicide, parasiticide, and human antimycotic was abandoned on account of its nephrotoxic side effects (see also nik-komycins, polyoxins). 

As Polyoxin A, P-81 with R, = CH3, R2 = R3 = OH C17H25N5O12 491.411 Nucleoside antibiotic. Produced by Strep-tomyces cacaoi var. asoensis. Antifungal agent. Amorph. powder. Sol. H2O poorly sol. MeOH, hexane. 

Garner s aldehyde is a key building block in the synthesis of chiral natural products [66]. It can be converted, for example, into a chiral 2-amino-l,3-dihydroxypropyl substructure (Scheme 4.94). This motif can be found in numerous natural products, such as in some imino sugars, the antifungal antibiotic polyoxin J, sphingosine, or the cytotoxic sphingosine derivative pachastrissamine. 

Staake M, Chauhan J, Zhou D, Shanker A, Chatteijee AD, Das S, Patterson SE. Phosphouoxius III synthesis of a-aminophosphonate analogs of antifungal polyoxins with anti-giardia activity. Org. Lett. 2010 12 45%-4599. 

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