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Thiostrepton, synthesis

Vancomycin was the first macrocyclic antibiotic evaluated as selector for the synthesis of HPLC chiral stationary phases (CSPs) [7], along with rifamycin B (among ansamycins) and thiostrepton (among polypeptides). [Pg.114]

Nicolaou, K.C. et al., Total synthesis of thiostrepton, Part 1 construction of the dehydropiperidine/thiazoline-containing macrocycle, Angew. Chem. Int. Ed., 43, 5087, 2004. [Pg.164]

Thiazolines can also be obtained through cyclodehydration of the compounds bearing C(=S)-NH-C-C-OH moiety (P-hydroxy thioamide). The utility of this strategy is demonstrated in the total synthesis of siomycin A, a member of the thiostrepton family <07TL1331 >. Exposure of thioamide 77 with DAST results in intramolecular cyclization to provide an excellent yield of thiazoline 78, which is converted to siomycin A in four steps. Compound 77 represents one of the most complex substrates for DAST-induced thiazoline formation. [Pg.227]

The same method has been applied to measure the Eli domain orientation when the protein is in complex with its RNA parmer or both RNA and thiostrepton antibiotic. The additional RDCs revealed a rearrangement of the N-terminal domain of Ell placing it closer to the RNA after binding of thiostrepton. HADDOCK has been used to calculate a model of the ternary stmcture of the Ell protein in complex with RNA and antibiotic. Based on the orientational data, the dynamics and the docking model, it seems that thiostrepton locks the domain conformation of Ell in a rigid (inhibitory) state. The antibiotic thiostrepton interferes with the interaction of elongation factors to this Ell-RNA region, which has a dramatic effect on the level of protein synthesis by the ribosome. [Pg.1287]

The first phase of the total synthesis of thiostrepton 303, a highly complex thiopeptide antibiotic, has been described. Retrosynthetic analysis of thiostrepton revealed units 304-308 as potential key building blocks. Concise and stereoselective constructions of all these intermediates have been achieved. The synthesis of the dehydropiperidine core 308 was based on a biosynthetically inspired aza-Diels-Alder dimerization of an appropriate azadiene system, an approach that was initially plagued with several problems which were, however, resolved satisfactorily by systematic investigations. The quinaldic acid fragment 305 and the thiazoline-thiazole segment 306 were synthesized by a series of reactions that included asymmetric and other stereoselective processes (Scheme 113) <2005JA11159>. [Pg.703]

The synthesis of the tetrasubstituted dihydroquinoline portion of siomycin Di, which belongs to the thiostrepton family of peptide antibiotics, was achieved in the laboratory of K. Hashimoto. The Jacobsen epoxidation was utilized to introduce the epoxide enantioselectively at the C7-C8 position. The olefin was treated with 5 mol% of Jacobsen s manganese(lll)-salen complex (R =f-Bu) and 4% aqueous NaOCI solution in dichloromethane. To enhance the catalyst turnover, 50 mol% of 4-phenylpyridine-A/-oxide was added to the reaction mixture. The desired epoxide was obtained in 43% yield and with 91% ee. [Pg.223]

Higashibayashi, S., Mori, T., Shinko, K., Hashimoto, K., Nakata, M. Synthetic studies on thiostrepton family of peptide antibiotics synthesis of the tetrasubstituted dihydroquinoline portion of siomycin Di. Heterocycles 2002, 57, 111-122. [Pg.608]

In 2005 Nicolaou et al. in the synthesis of thiostrepton utilized reaction of 37 and DBU at ambient temperature to form allylic epoxide 38 in 96% yield.25... [Pg.420]

Thiopeptide antibiotics, thiazolyl peptides, naturally occurring sulfur-containing, highly modified, macrocyclic peptides. They share a number of structural motifs, including several heterocycles such as thiazoles, a dehydropiperidine, a pyridine, oxazoles, and indoles. Nearly aU of the thiopeptide antibiotics act as inhibitors of protein synthesis in bacteria. They are secondary metabolites produced by actino-mycetes, largely by the genus Streptomyces. A representative member of this family is thiostrepton [M. C. Bagleyetal., Chem. Rev. 2005, 105, 685]. [Pg.371]

Thiostrepton, an important member of the thiopeptide antibiotics because of its biological and medical value. It was first isolated as early as 1954 from Streptomyces azureus. It is used in animal health care as a topical antibiotic. However, its application in humans is limited by its low solubility and bioavaUability which led to development of drug resistance by the proliferating bacteria. The total synthesis was described in 2005 [Y. Xing, D. F. Draper, Biochemistry 1996, 35, 1581 K. C. Nicolaou etal.,J. Am. Chem. Soc. 2005, 127, 11159]. [Pg.371]

The Boekelheide reaction was applied by the Nicolaou groups in the synthesis of a model system of the thiopeptide antibiotic thiostrepton (302). The tetrahydroquinoline 303 was converted into the A -oxide by /w-CPBA oxidation followed by treatment with TFAA and then hydrolysis to afford key intermediate alcohol 304 as a diastereomeric mixture. [Pg.451]

Nicolaou and co-workers revisited these general conditions during their landmark total synthesis of thiostrepton. Notable features in ring construction during this synthesis include higher reaction temperatures than those used in the Meyers method and the isolation of the crude hydroxythiazoline before the elimination step, which was then conducted employing TFAA in the presence of pyridine followed by triethylamine. These reaction conditions also led to A -trifluoroacetylation of the free —NH... [Pg.301]

A large volume of work continues to be published in the area of thiazole chemistry. Physicochemical aspects continue to receive their share of attention, and interest in meso-ionic compounds has been sustained. Asinger and Offerman s versatile synthesis provides routes to reduced thiazoles (75, 212—217). Other notable methods employ thiirans (75, 218, 219), thiocarbonylamino-acid silyl esters (75, 220), and enamines (75, 221) as starting materials. Reduced thiazoles play an important role in peptide and protein studies (75, 234—239), and generate interest because of their occurrence as structural units in compounds of physiological interest, such as the antibiotics bacitracin A (75, 147 - 149) and thiostrepton. Benzothiazole derivatives have been employed to separate amidines for the first time into their syn- and fl/itZ-isomers (74, 49). The reaction of citric acid with penicillamine provides an interesting entry into the thiazolo-[3,2-fl]pyridine system (74, 152). [Pg.861]


See other pages where Thiostrepton, synthesis is mentioned: [Pg.153]    [Pg.115]    [Pg.108]    [Pg.264]    [Pg.153]    [Pg.210]    [Pg.137]    [Pg.328]    [Pg.244]    [Pg.199]    [Pg.394]    [Pg.395]    [Pg.401]    [Pg.401]    [Pg.40]   
See also in sourсe #XX -- [ Pg.451 ]




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