Thiazolyl peptides

In the synthesis of the thiazolyl peptide GE2270 A (111), developed by Bach and coworkers, a remarkable intra-molecular Stille reaction on 109 leads to macrocycle 110 in a highly efficient manner (Scheme 5.4.21).ii6... 

Scheme 5.4.21 Intramolecular macrocycllzatlon by using the Stille reaction In the synthesis of the thiazolyl peptide CE2270 A (TBDMS tert-butyidimethylsllyl)...

Nocathiacins. Leet and co-workers reported the isolation and characterization of several new thiazolyl peptide antibiotics from Nocardia sp. The authors utilized long-range HMBC data in the determination of the structure of nocathiacin-I (111) but... 

GE2270A (62) was isolated from a strain of Plambispora rosea and belongs to the thiazolyl peptide family of antibiotics inhibit protein synthesis. It binds to the 23S rRNA and blocks the action of the elongation factor EF-The compound exhibits excellent activity against Gram-positives, including resistant strains, in experimental mice models of Streptococci endocarditis. ... 

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]. 

Another example of a well-established class of natural products containing the thiazole heterocycle is the thiopeptide antibiotics. Often referred to as thiazolyl peptides, most of these highly modified, macrocyclic peptides inhibit protein synthesis in bacteria. They display a high inhibition... 

The vicinal proton-proton couplings have been employed by Heckmann and Bach to prove the absolute configuration of the thiazolyl peptide GE2270A isolated from Planobispora rosea. 

They are easily prepared from dithiocarbamate and nickel(ll) salts, and examples including those derived from simple amines (587,1472) fluorinated amines (76) amines with (O-hydroxyl groups (1473) indole (341) indoline, carbazole, and imidazole (342) (72) together with those with heterocyclic (72,1116,1126,1424,1474) benzyl (346,1475) and aryl (95,1423,1425,1476, 1477) substituents. Others include examples prepared from Schiff bases (1121), 2-aryldecahydroquinolin-4-ones (1478), tetrahydroquinoline and tetrahydroiso-quinoline (1479), succinimide and phthalimide (49), l,4,7,10-tetraoxa-13-aza-cyclopetadecane (50), 1,3,4-thiazolyl (1426), and 3-dithiocarboxy-3-aza-5-aminopentanoate (343) (1480,1481). A wide range of amino acid derivatives have also been prepared (122,133-137), as have derivatives of glycine, DL-alanine and DL-valine peptide bonded to ethyl esters of a-amino acids (134). 

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