Nosiheptide

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. 

Nosiheptide S. ctuosus Macrolide CMH43N,30i2Se 1222 242, 322 CHCI3, DMF, MeOH, EtOH, H2O, petroleum... 

Nosiheptide Animal tissues DMF/acetone extn, centrgn S. ureus ATCC 6538P 142 ... 

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

Nosiheptide. [Mitsubishi Kasei] Feed additive, growth promotn for swine and poultry. 

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. ... 

Thiostrepton (bryamycin, thiactin). C72H85N19O18S5, Mr 1664.91, mp. 246-255 C, [a]go -98.5 (CH3COOH), a bicyclic thiopeptide produced by Streptomyces aureus with activity against Gram-positive bacteria and used as a fodder additive in animal breeding. T. inhibits protein biosynthesis, the mechanism of action corresponds to that of the structurally related nosiheptide. The biosynthesis of T. is the subject of intense investigation, it is assumed that the core peptide chain is formed non-ribosomally via a multi-enzyme complex. 

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. ... 

Previous studies have determined which amino acids are incoqx rated into thiostrepton (55) and nosiheptide (56) by feeding isotopically labeled amino acids to the producing... 

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