Cyclic hexadepsipeptide

Resistance to streptogramin type B antibiotics can be mediated in staphylococci and enterococci by plasmids carrying a vgb gene [2]. The Vgb enzyme is a lyase that linearizes the cyclic hexadepsipeptide by cleavage of the ester bond via an elimination reaction. 

The enniatins and beauveracin are cyclic hexadepsipeptides and so are 18-membered macrocycles built up of alternating amino acid and carboxylic acid residues. They exhibit lower selectivity than (137) and consequently are more broad spectrum ionophores. The structure of (138)KI has been solved544 but it was not possible to conclude, with certainty, whether the metal is entrapped in the central cavity, as in related cyclic polyether structures (Figure 14a), or whether it occupi.es a site between two adjacent ligand molecules to give an infinite sandwich (147) as has been found in the RbNCS complex of a synthetic ldlldl isomer of (138).545 Adducts of 1 2 sandwich and 2 3 club sandwich stoichiometry have been proposed for Cs+ complexes of (138),546a and the 1 2 K+ sandwich complex of (138) has been proposed as the species which transports K+ across lipid layers as it shields the metal effectively from solvent interactions.5461 ... 

In 1959 Shchukina et a I. 56 showed that the addition of pyridine to DCC increases the yield (65-85%) of depsipeptides constructed from Z-protected amino acids and serine, threonine, or salicylic acid derivatives. The ferf-butyl ester of Af-(benzyloxycarbonyl)-leucylleucic acid (Table 2) was prepared in 60% yield under the same conditions of addition using a 2 molar excess of pyridine to carbodiimide. 57 The DCC/pyridine technique was successfully utilized in the ring closure between ()-alanine and leucic acid residues during the synthesis of the cyclic hexadepsipeptide destruxin B.[58 Under this modified approach the... 

The polychlorinated cyclic hexadepsipeptides kutznerides 1-9 (1036-1044), which contain both the novel 6.7-d i c h I oroh e x ah yd ropy rro I o 12.3 -/< i n do I e core and several unusual amino acids, are found in the actinomycete Kutzneria sp. 744 inhabiting the roots of Picea abies (1071,1072). These compounds show moderate activity against root-rotting fungi. Another chlorinated he xahydropvitoIo12.37 indole cyclohexapeptide is the dimeric chloptosin (1045) isolated from a Streptomy-... 

Standard procedures were followed for isolation of the toxic principles from mycelium of FA 120. A methylene chloride extract of the freeze-dried hyphae was initially partitioned between hexane and aqueous methanol to separate lipids from more polar material. Bio-assay-monitored chromatographic fractionation of the hexane-soluble material led to the isolation of a fraction (ca. 5% of the hyphal weight) which could account for much of the toxicity of the hyphae of FA 120 to spruce budworm larvae. The spectroscopic and chemical properties of this material were characteristic of the enniatins, a group of cyclic hexadepsipeptide ionophore antibiotics produced by several plant pathogenic Fusarium species, including F. lateritium... 

The enniatins enniatin A [2505-15-1], C3(,H63N309, enniatin B [917-13-5], C33H57N309, enniatin C [19893-23-3], C36H63N309, and beauvericin (Fig. 8) are 700—800 molecular weight cyclic hexadepsipeptides. They form valinomycinlike hydrophilic cavities surrounded by outer lipophilic regions, but they have more flexible structures than those seen with valinomycin and therefore have less specificity for potassium over sodium ion than valinomycin (186,187). 

The association constant for ion binding of Cyclo-(Pro-Gly)3 is nearly the same as that of antamanide, but the selectivity for Ca of Cydo-(Pro-Gly)3 is inferior to that for Na" " of antamanide 144). Cyclo-(Pro-Gly)3 resembles the K -specific cyclic hexadepsipeptide aiitibiotic enniatin 145), in the aspect that both cyclic compounds form sandwich-type comidexes with ions. It is very likely that Cyclo-(Pro y)3 transports ions across a membrane via the formation of a club sandwich-type complex. The metal-ion complex of Cydo-(Proextractable with water from organic phase. A specific behavior of Cyclo Pro-Gly)3 in the ion tran rt throu a membrane is expected from this property. 

Enniatin B is a cyclic hexadepsipeptide the smaller ring results in a relatively planer array of ligetnding oxygen atoms the more open lnd more flexible cage results in a IC " Na" " discrimination of only 3 1 (j6). 

Kutznerides a-i are antifungal and antimicrobial cyclic hexadepsipeptides isolated from the soil actinomycete Kutzneria sp. 744. These metabolites are... 

Enniatin B (Fig. 2B) is a cyclic hexadepsipeptide The ring, which is only half the size of that of valinomycin, is too small to fold into the bracelet conformation of valinomycin and forms a staggered plane The complexing cage is consequently less well defined and the K -.Na selectivity (K Na 3 1) is considerably attenuated... 

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