Polyether antibiotics stability

In the Ba2+ complex with (145), two anions coordinate to the cation in different ways (Figure 32b). The metal ion sits primarily in a cavity provided by one of the anions and is six-coordinated by two ether, two hydroxy, one keto and one carboxylate oxygen atoms. A nine-fold coordination is completed by further coordination to two oxygen atoms from the second anion and a water molecule. 73 A review of the structures of polyether antibiotic complexes is available and includes a compilation of structural data.372 The stoichiometries of alkali and alkaline earth complexes of (145) in methanol, have been determined potentiometri-cally and show 1 1 neutral complexes for the alkali metal cations, and high stability 1 1 (charged) and 1 2 (neutral) complexes for the alkaline earth cations.574... 

Because the stability constant of its complex with potassium is much greater than that with sodium, valinomycin is a relatively specific potassium ionophore. In contrast, the mushroom peptide antamanide has a binding cavity of a different geometry and shows a strong preference for sodium ions.388,390 The structure of the Na+-antamanide complex is also shown in Fig. 8-22B. The Streptomyces polyether antibiotic monensin (Fig. 8-22D),389,391 a popular additive to animal feeds, is also an ionophore. However, its mode of action, which involves disruption of Golgi functions, is uncertain 392... 

Cations are known to be transported through membranes by synthetic macrocyclic polyethers as well as by antibiotics. When the rate-determining step is the ion extraction from the IN aqueous phase to the membrane phase, the transport rate increases with the increasing stability constant. On the other hand, when the rate-determining step is the ion-release from the membrane phase to the OUT aqueous phase, the carrier must reduce the stability constant in order to attain efficient decomplexation. Some polyether antibiotics feature... 

The greater reactivity of MPM ethers widi respect to unsubstituted benzyl ethers and aliphatic ethers can be attributed to the increased stabilization by the 4-medioxy substituent of a catitmic intermediate of type (36 Scheme 6). The selectivity between these groups has been ermloited in the synthesis of a variety of natural products, including octosyl acid A, oligosaccharides, - inositol jdiosphates, - and the polyether antibiotics X-206 and salinomycin (equation 28). ... 

Thermodynamic data have also been reported for the binding of the alkali metals with the two isomers of the cyclic polyether 2,5,8,15,18,21-hexaoxatricyclo[20,4,0,0 ]hexacosane (4). The stability order of these metal ions with either isomer is identical to the permeability order for the same metals with the structurally related antibiotics (lb) and (3) i.e. K+ > Rb+ > Cs > Na+, Li+. 

---