Nosiheptide antibiotic

Thiostrepton family members are biosynthesized by extensive modification of simple peptides. Thus, from amino acid iacorporation studies, the somewhat smaller (mol wt 1200) nosiheptide, which contains five thiazole rings, a trisubstituted iadole, and a trisubstituted pyridine, is speculated to arise from a simple dodecapeptide. This work shows that the thiazole moieties arise from the condensation of serine with cysteiae (159,160). Only a few reports on the biosynthesis of the thiostrepton family are available (159,160). Thiostrepton is presently used ia the United States only as a poly antimicrobial vetetinary ointment (Panalog, Squibb), but thiazole antibiotics have, ia the past, been used as feed additives ia various parts of the world. General (158) and mechanism of action (152) reviews on thiostrepton are available. 

Related Pd-cyclizations have been applied to the synthesis of 3-carboethoxy-2-trifluoromethylindoles [367, 368] and 2-carbobenzyloxy-4-hydroxymethyl-3-methylindoles, a unit that is present in the antibiotic nosiheptide, from a 2-(2-iodoanilino) unsaturated ester [369]. A nice variation utilizes the in situ synthesis of 2-iodoanilino enamines and subsequent cyclization [370] as shown below. 

Koerber-Ple, K. Massiot, G. Synthesis of an unusual 2,3,4-trisubstituted indole derivative found in the antibiotic nosiheptide. Synlett 1994, 759-760. 

The 3,4-disubstituted indole-2-carboxylate ester 45, which is encountered as part of the antibiotic nosiheptide, was obtained starting with the condensation of aniline 43 with benzyl 2-oxobutanoate. After protection of the hydroxyl group, Heck cyclization occurred in 46% yield. <94SL761>... 

Micrococcin Pj. C4gH4,N,30,S , Mr 1144.36, mp. 252°C (decomp.), [a] +1 i6° (90% C2H5OH). A peptide antibiotic isolated from the culture broth of Bacillus pumilus as main component of the micrococcin P complex. For synthesis see Zir.. Closely related with M. is the antibiotic nosiheptide. ... 

Cyclic depsipeptide antibiotic. Prod, by the proposed genus Sehekia sp. Active against gram-positive bacteria. Related to Antibiotic S 54832A, A-02301 and Nosiheptide, N-00824. 

The Holzapfel-Meyers-Nicolaou modification is a significant improvement over the traditional Hantzsch conditions. However, racemization can still occur in some circumstances. For example, the two-step Hantzsch reaction of thioamide 20 with bromide 19 furnishes thiazole 21 with 60-85% enantiomeric excess due to partial epimerization at the a-stereogenic center. The epimerization issue is obviated when thioamide 20 is replaced with the ketal-protected thioamide 22. Reaction of 19 with 22 delivers 23 with good optical purity (> 96% ee). This thiazole represents the core structure of the potent thiopeptide antibiotic nosiheptide. ... 

Clearly, numerous biosynthetic reactions are required to synthesize thiopeptide antibiotics. The amino acid compositions of thiostrepton and nosiheptide were determined by feeding experiments, but these studies could not provide information about the... 

Houk DR. Studies on the biosynthesis of the modiffed-peptidc antibiotic, nosiheptide. Ph.D. dissertation. The Ohio State University, 1986. 

Mucck U, Knaggs AR, Tsuchiya R, Nguyen T, Beale JM. Floss HG. Biosynthesis of the modified peptide antibiotic nosiheptide in Strepiumyces actuosus. J Am Chem Soc 1993 115 7557-7568. 

Nosiheptide (a gram positive polypeptidic antibiotic) was extracted from meat and eggs and analyzed on a 40°C Cjg column (A = 357 nm, ex 500 nm, em). A... 

The spectrum of nosiheptide, an antibiotic structurally related to thiostrepton... 

Depaire, H., J.-P. Thomas, and A. Brun The Structure Relationship between the Antibiotics Nosiheptide and Thiostrepton. Tetrahedron Letters 1977, 1403. 

Pascard, C., a. Ducruix, J. Lunel, and T. Prange Highly Modified Cysteine-Containing Antibiotics. Chemical Structure and Configuration of Nosiheptide. J. Amer. Chem. Soc. 99,6418 (1977). 

Prang6, T a. Ducruix, C. Pascard, and J. Lunel Structure of Nosiheptide, a Polythiazole-Containing Antibiotic. Nature 265, 189 (1977). 

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