Chlorothricin

Chlorothricolide, the aglycon of the chlorothricin antibiotic, is a complex molecule containing an octahydronaphthalene unit. Roush and Sciotti [121] recently reported the total enantioselective synthesis of chlorothricolide. The multiple Diels-Alder reaction between poliene 130 and chiral dienophile (R)-131 was the key step in the synthetic process (Scheme 2.50). The interaction... 

Compound MC-033 (205), structurally similar to chlorothricin, has been isolated from a cultured broth of Streptomyces sp., and inhibits the biosynthesis of cholesterol from mevalonate with an IC50 value of 1.05 x 10° M [163]. 

S. antibioticus produces another unusual macrolide antibiotic [45] called chlorothricin (57) containing, in addition to the aglycone (modified methylsalicylic acid), saccharides, dideoxyhexoses in the first place. Their biosynthesis was investigated by the incorporation of stable isotopes [45-47]. The compounds were only active in a synthetic medium and inactive in a complex one [48]. Compounds designated MC031-034 (58-61) are similar to chlorothricin mentioned above and were isolated from the cultivation broth of Streptomyces sp. collected in Japan. Another compound, 2-hydroxychlorothricin (62), with antitumor activity, was isolated [66] from Streptomyces K818. 

Macrolide antibiotics contain a wide spectmm of deoxysugars which are biosynthesized on different pathways [41]. For chlorothricin (O Fig. 6) for example, the stereochemical course... 

Keller-Schierlein, W., Muntwyler, R., Pache, W., and Zaehner, H. (1969). Metabolic products of microorganisms. LXXIII. Chlorothricin and dechlorothricin. Helv. Chim. Acta 52, 127-142. 

A number of total syntheses of decalin polyketides have been reported, supporting the feasibility of biosynthetic cycloadditions. Actual involvement of PKS (lovastatin PKS and chlorothricin PKS) and PKS-NRPS (cheaoglobosin PKS-NRPS and equisetin PKS-NRPS) as Diels-Alderases is discussed in Section 8.08.4. Intramolecular Diels-Alder reaction could occur either during or after chain elongation of polyketide chain. 

The rapid progress in polyketide biosynthesis allowed to identify the biosynthetic gene clusters of several Diels-Alder adducts such as equisetin, chaetoglobosin, spinosyn, chlorothricin, and kijanimicin. Possible enzymes that catalyze the corresponding Diels-Alder reaction in the biosynthesis of these polyketides will be discussed. 

CjoH 3C10,6, Mr 955.49, crystalline, mp. 206-207°C, antibiotic against Gram-positive bacteria from Strep-tomyces antibioticus. C. occurs as a mixture with de-chlorothricin. Both compounds represent diprotic acids. C. acts as an inhibitor of pyruvate carboxylase and malate dehydrogenase. The aglycone is (-)-chlorotri-colide. ... 

A study of the biosynthesis of the sugar units in chlorothricin has shown that formation of the 2.6-dideoxy-D-arabino-hexose units involves replacement of the 2-hydroxy group in glucose by hydrogen... 

No feeding experiments aimed at establishing the biosynthetic origin of the carbon atoms of TMN have been performed. Only a very limited number of studies performed on TSN or other antitumor antibiotic bearing tetronic acid moieties (4-hydroxy-[5//]furan-2-one) such as chlorothricin have been reported. Thus, the carbon skeleton of TSN is shown to consist of a polyketide chain derived from seven acetate units and six propionate units, combined with a C2 unit of unknown... 

In 2006, in a paper in which was reported the chlorothricin gene cluster, it was proposed that the precursor to the antibiotic is assembled by a modular PKS, and the full-length chain is transferred from the PKS by transesterification to an unusual enoylpyruvoyl-ACP unit [274],... 

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