Depsipeptides cyclo

Cyclic peptides are important biologically active compounds that combine peptide properties with conformational bias and often improved serum stability and membrane penetration [1-3]. Depsipeptides are similar compounds, but they contain as part of their backbone one or more hydroxylated amino acid residues that add ester or lactone moieties to the peptide (Fig. 1) [4-6]. Cyclo- and... 

The antibiotic viscosin from Pseudomonas viscosa (Scheme 8) is a cyclo-depsipeptide acyl-ated at the N-terminus with D-3-hydroxydecanoic add.[103 112] The C-terminal carboxy group is esterified with the hydroxy group of the Thr3 residue. The synthesis of this natural product presents the problem of an ester ring closure and was performed in two steps with initial solid-phase synthesis of the Thr3-0-branched linear intermediate followed by ring closure with formation of the amide bond.1 131... 

More yS-amino acids are, apparently, special building blocks within natural (cyclo)peptides and depsipeptides [11]. It is not dear whether Nature aimed at an increase of proteolytic stability or at conformational modification. Chemists, however, followed this example of natural / -amino acid chemistry decades ago and started to modify known a-peptides by substitution of solitary a-amino adds with p-amino acids [12]. One major issue of this synthetic analoging was to increase the proteolytic stability of peptides [13, 14] with regard to peptidases [15]. A second goal was the controlled conformational tuning of cyclo-a-peptides with / -amino acid modifications. 

R129 P. Jeschke, W. Etzel, A. Harder, M. Schindler, A. Gohrt, U. Pleiss, H. Kleikauf, R. Zocher, G. Thielking, W. Gau and G. Bonse, Cyclo-depsipeptides From Natural Product to AnthelminticaUy Active Synthetic Enniatins , p. 207... 

Apart from studies on avermectins, paraherquamide and some cyclo-depsipeptides, few attempts to delineate the mode of antinematodal action of the metabolites contained in this review have been undertaken. Currently, there are three classes of broad spectrum anthelmintics in use the benzimidazoles, the levamisoles and the avermectins. However,... 

The reaction of 2 with 3-(dimethylamino)-2,2-dimethyl-2//-azirine (83) affords in 94% yield the diamide (R)-( — )-2-(2-hydroxy-2-phenylacetamido)-A, A -2-trimethylpropionamide (84). Selective acidic hydrolysis of 84 with gaseous hydrogen chloride in acetonitrile-water provides the acid 85. The hydroxyl group is protected as a THP ether and the compound is converted to the depsipeptide 86 in good yield. Cyclization of 86 occurs with gaseous hydrogen chloride in toluene at 100 °C to furnish in 88% yield cyclo[(7 )-Mns-Aib-(7 )-... 

Enniatin family, cyclic depsipeptides produced by strains of Fusarium. Members are enniatin A, cyclo-(-D-Hiv-Me-Ile-)3, enniatin B, cyclo-(-D-Hiv-MeVal-)3, and enniatin C, cyclo-(-D-Hiv-MeLeu-)3, enniatin D, cyclo-(-D-Hiv-MeLeu-D-Hiv-MeVal-D-Hyv-MeVal-), enniatin E, cyclo-(-D-Hiv-MelLe-D-Hiv-MeLeu-D-Hiv-MeVal-), and enniatin F, cyclo-(-D-Hiv-MeLeu-MeIle-D-Hiv-Melle-) which all contain D-a-hydroxyisovaleric acid (o-Hiv) besides various L-methylamino acids. Enniatins act as ionophores to form complexes with K+ ions which allow their transport across membranes. 

Montanastatin, cyclo-(-D-Hiv-D-Val-Lac-Val-)2, a member of the depsipeptides isolated in only low yield from a culture of the soil-dwelling eubacteria Streptomyces anulatis collected in Montana together with valinomycin. Montanastatin is a cyclic dimer of the sequence shown in brackets, whereas valinomycin is a cyclic trimer . Due to the smaller ring size, montanastatin shows none of the antimicrobial activity exhibited by valinomycin [G. R. Pettit et al., Bioorg. Med. Chem. 1999, 7, 895]. 

Enniatins ring-shaped depsipeptide antibiotics produced by the fungus Fusarium orthoceras var. en-niatum and other Fusaria. Enniatin A, cyclo-(-D-Hyv-MeIle-)j and enniatin B, cyclo-(-D-Hyv-MeVal-)3... 

Valinomycin cyclo-(-D-Val-Lac-Val-D-Hyv-)j, an antibiotic, cyclic depsipeptide, especially active against Mycobacterium tuberculosis. In addition to valine, it contains the heterocomponents, L-lactic acid (Lac) and n-a-hydroxyisovaleric acid (o-Hyv). It is an lonophore (see), which selectively transports potassium ions across membranes. 

De Silva, E.D., Andersen, R.J., and Allen, T.M. (1990) Geodiamolides C to F, new cytotoxic cyclo-depsipeptides from the marine sponge Pseudaxinyssa sp. Tetrahedron Lett., 31, 489 92. 

Onchidin is cyclo(Meval-Amo-Val-Hiv-Hiv-MevabAmo-VabHiv-Hiv). It is the first example of a dimeric depsipeptide isolated from a mollusk. Meval is N-methylvaline and Hiv is 2-hydroxy-isovaleric acid. 

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