Nystatin synthesis

Nucleoside antibiotics biosynthesis, 1, 88-90 Nucleosides oxa analogues, 3, 1085 as pharmaceuticals, 1, 153 protected, 5, 316 Nucleosidin occurrence, 5, 603 Nupharolutine synthesis, 2, 393 Nybomycin applications, 6, 667 Nybomycin, deoxy-applications, 6, 667 Nystatin antifungal agent veterinary use, 1, 211... 

As an example of the usefulness of the Sharpless asymmetric epoxidation the enantioselective synthesis of (-)-swainsonine and an early note by Nicolaou on the stereocontrolled synthesis of 1, 3, 5...(2n + 1) polyols, undertaken in connection with a programme directed towards the total synthesis of polyene macrolide antibiotics, such as amphotericin B and nystatin Aj, will be discussed. 

We will describe here the first method as developed by Nicolaou [2] which has recently been applied to the synthesis and stereochemical assignment of the C(l)-C(10) fragment of nystatin Aj (2) [5]. 

HANSCH GM, GEMSA D, RESCH K. Induction of prostanoid synthesis in human platelets by the late complement components CSb-9 and the channel forming antibiotic nystatin inhibition of the recyclation of liberated arachidonic acid. J Immunol 135 1320-1324,1986. 

A recent example involves the synthesis of N-glycosyl derivatives of polyene macrolide antibiotics, such as the preparation of N-(deoxyfructosyl)nystatin (128) by reaction of nystatin with (+)-glucose (Scheme 30)."°... 

C. Nystatin decreased synthesis of ergosterol in fungal cell membranes... 

It has been reported that between 10 and 20 min after candicidin treatment of yeasts that protein syntheses slowed and then ceased. Protein synthesis slowed not as a result of energy deficiency, as ATP was abundant in polyene-treated cells at this stage, but as a direct result of reduced potassium levels [287]. Similar reductions in protein syntheses have been observed in E. coli mutants with defective potassium transport systems [291]. Upon treatment with levels of nystatin that did not affect yeast respiration, the uptake of glycine was rapidly reduced and ceased within 20 min of antibiotic application. Low nystatin concentrations did not produce leakage of amino acids into the environment, suggesting that nystatin at high concentrations damaged the cell membrane to such an extent that all normal uptake processes ceased [292]. 

Significant reduction in serum cholesterol levels can also be demonstrated in animals simultaneously fed polyenes and high sterol diets. Dogs appeared more able to maintain their serum cholesterol levels when fed sterols and filipin, amphotericin B or candicidin [145,535] but nystatin had no effect. The anti-hypercholesterolemic effect was not simply due to the prevention of sterol uptake [538,539]. A consequence of the excretion of sterol-polyene complexes in the faeces is the loss of bile salts (which are steroids) and this tends to remove sterol from the body. This resulted in increased hepatic synthesis, increased utilization of adipose fat and reduced sebum levels. Candicidin has been suggested as an antihypercholesterolemic agent in man [546]. 

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