Polyenes Polyether antibiotics

The first polyether antibiotic to be isolated was nigericin 1 in 1951. By 1983, more than 70 terrestrial polyether antibiotics had been reported and Cane et al. (1) had proposed a unified stereochemical model to account for their biosynthesis, including the polyene-polyepoxide model of polyether formation. It took almost 20 years for the first polyether gene cluster to be reported (2). In contrast, the first marine polyethers were reported in 1981, and a model to explain the biosynthesis of marine polyether ladder compounds was proposed in 2006 (3) no genetic information is available currently for the marine polyethers. 

A different mechanism was adopted in the biosynthesis of cyclic polyethers such as monensin. These PK-derived polycycles are formed in a cascade fashion with other enzymatic transformations. For example, in the biosynthesis of monensin (Equation 8.2), the cascade polyether formation is triggered by epoxidation of a polyene template [40]. Similar mechanisms can probably be used to make other polyether antibiotics containing tetrahydrofurans and tetrahydropyrans [41]. 

The antibiotic aurocitrin (178) has been synthesized using a Wittig reaction of the dienylidene ylide (177). A series of PO-olefinations have been used to construct the polyene system (179), which, after suitable modification, was cyclized to (180) in a trial of a new approach to the synthesis of the polyether antibiotic X-14547A. ... 

Substances of the amphotericin D (a polyene), polyether (for example crown cyclic ethers), Antamanide (a peptide), and valinomycin (a depsi-peptide) represent structural types capable of complexing with alkali metal ions and thereby promoting their dissolution in fairly nonpolar solvents. Such compounds are known as ion carriers and some display antibiotic properties which may in part reside with activity in natural membranes. In order to evaluate structural changes upon such interesting functions, Gisin and Merri-field have synthesized a cyclododecapeptide (Chart 15) where the D-a-hy-droxyisovaleric acid and L-lactic acid units of valinomycin were replaced respectively with D-Pro and L-Pro. In MeCl-Aq the valinomycin analog was found to exhibit a seven times greater affinity for potassium picrate (to form a 1 1 hydrophobic complex) than that of the parent depsipeptide. 

Structures of antibiotics vary widely they can be divided into peptide, macrolide, aminoglycoside, nucleoside, oligosaccharide, polyether, sesquiterpene and polyene compounds, and many more. 

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