Depsipeptides, cyclic

Cabaret, D. Adediran, S. A. Garcia Gonzalez, M. J. Pratt, R. F. Wakselman, M. Synthesis and reactivity with P-lactamases of penicillin-like cyclic depsipeptides. J. Org. Chem. 1999, 64, 713-720. 

Especially sensitive and selective potassium and some other ion-selective electrodes employ special complexing agents in their membranes, termed ionophores (discussed in detail on page 445). These substances, which often have cyclic structures, bind alkali metal ions and some other cations in complexes with widely varying stability constants. The membrane of an ion-selective electrode contains the salt of the determined cation with a hydrophobic anion (usually tetraphenylborate) and excess ionophore, so that the cation is mostly bound in the complex in the membrane. It can readily be demonstrated that the membrane potential obeys Eq. (6.3.3). In the presence of interferents, the selectivity coefficient is given approximately by the ratio of the stability constants of the complexes of the two ions with the ionophore. For the determination of potassium ions in the presence of interfering sodium ions, where the ionophore is the cyclic depsipeptide, valinomycin, the selectivity coefficient is Na+ 10"4, so that this electrode can be used to determine potassium ions in the presence of a 104-fold excess of sodium ions. 

Larvae of the tunicate Trididemnum solidum are most likely protected by didemnins like 44-46, cyclic depsipeptides that were initially identified from adults of this species [92]. The larvae are highly unpalatable to the wrasse Thalassoma bifasciatum, which rejected the larvae while readily consuming krill eyes that served as larval mimics. Coating one krill eye with the lipid soluble compounds from a single T. solidum larva rendered it as unpalatable as the larvae themselves. Reduced feeding was also observed when didemnin B (45) and nor-didemnin B (46) were administered to reef fishes in the field (Scheme 12) [92]. 

R.W. Sparidans, J.H.M. Schellens, L. Lopez-Lazaro, J.M. Jimeno and J.H. Beijnene, Liquid chromatographic assay for the cyclic depsipeptide aplidine, a new marine antitumor drug, in whole blood using derivatization with t/rms-4 -hydrazme-2-stilbazole. Biomed. Chromatogr 18 (2004) 16-20. 

Plitidepsin (Aplidin) (203) Cyclic depsipeptide Plitidepsin (Aplidin ) (203) Oncology Inhibitor to VEGF, VEGFRLandGl/ G2 phase cell cycle Phase II PharmaMar 934-936... 

Conversion of Cyclic Peptides into Cyclic Depsipeptides by N—>0 Acyl Shift... 

Gerard, J. Lloyd, R. Barsby, T. Haden, P. Kelly, M.T. Andersen, R.J. (1997) Massetolides A-H, antimycobacterial cyclic depsipeptides produced by two pseudomonads isolated from marine habitats. J. Nat. Prod., 60, 223-9. 

Kalinovskaya. N.I. Kuznetsova, T.A. Rashkes, Ya.V. Mil grom, Yu.M. Mil grom, E.G. et al. (1995) Surfactin-like structures of five cyclic depsipeptides from the marine isolate of Bacillus pumilus. Russ. Chem. Bull., 44, 951-5. 

Ohno, O., Ikeda, Y., Sawa, R., Igarashi, M., Kinoshita, N., Suzuki, Y., Miyake, K., and Umezawa, K. (2004). Isolation of heptadepsin, a novel bacterial cyclic depsipeptide that inhibits lipopolysaccharide activity. Chem. Biol. 11,1059-1070. 

This method was used widely and successively in the synthesis of cyclic depsipeptide antibiotics and natural metabolites such as sporidesmolids I-IV,126-291 angolide,13(11 enniatins A... 

Scheme 14 Route to Cyclic Depsipeptides via Direct Amide CyclizationI1141...

Scheme 15 Route to Cyclic Depsipeptides through Acyl Peptide Cesium Salt 1161...

The majority of the early procedures for the cleavage of the (3-lactams /Vj-CT bond deal with hydrolysis and alcoholysis processes under rather harsh acid or basic reaction conditions. One example is the ring opening of (3-lactam 2 under acidic conditions to afford almost quantitative (3-amino ester 3, a component of the dimeric cyclic depsipeptide onchidin, 1, isolated from the marine mollusc Onchi-dium sp., Scheme 1 [54]. 

Tabudravu JN, Morris LA, Milne BF, Jaspars M (2005) Conformational Studies of Free and Li+ Complexed Jasplakinolide, a Cyclic Depsipeptide from the Fijian Marine Sponge... 

Rouhiainen L, Paulin L, Suomalainen S, Hyytiainen H, Buikema W, Haselkom R, Sivonen K (2000) Genes Encoding Synthetases of Cyclic Depsipeptides, Anabaenopeptilides, in Anahaena Strain 90. Mol Microbiol 37 156... 

Rashid MA, Gustafson KR, Cartner LK, Shigematsu N, Panned LK, Boyd MR (2001) Microspinosamide, a New HIV-Inhibitory Cyclic Depsipeptide from the Marine Sponge... 

Matem U, Oberer L, Falchetto RA, Erhard M, Konig WA, Herdman M, Weckesser J (2001) Scyptolin A and B, Cyclic Depsipeptides from Axenic Cultures of Scytonema hofmanni PCC 7110. Phytochemistry 58 1087... 

Didemnin B (347) is a cyclic depsipeptide isolated from the Caribbean tunicate Trididemnum solidum and is currently in phase II clinical trials as an anticancer agent. Didemnin B also shows antiviral and immunosuppressive activity. The structure of didemnin B was revised to 347 containing... 

The biosynthetic studies undertaken to date on microbial marine natural products well illustrate the diversity of metabolic pathways encountered in cultured marine bacteria. Examples include brominated alkaloids such as pentabromopseudiline (Structure 2.1),19 polyketide or mixed polyketide metabolites such as oncorhyncholide (Structure 2.2),20 aplasmomycin (Structure 2.3),21 and andrimid (Structure 2.4),22 or the cyclic depsipeptide salinamide A (Structure 2.5).23 As researchers continue to define more specific culture media and a wider range of marine bacteria from diverse habitats are successfully placed into culture, the true biosynthetic potential of these prolific and adaptable microorganisms can be explored. 

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