Ansamycins ansamitocins

A novel ansamycin, naphthomycin K (1641), was isolated from a Streptomyces strain of the medicinal plant Maytenus hookeri (1616). This compound was cytotoxic (P388 and A-549 cell lines) but inactive against Staphylococcus aureus and Mycobacterium tuberculosis. An Amycolatopsis sp. has furnished the ansacarbami-tocins A-F, Al, B1 (1642-1649), which are similar to the ansamitocins (1617). 

Ansamycin antibiotics are probably the most complex organic compounds produced by the genus Streptomyces. In addition to the antibacterial, they also exhibit antiviral effects. Ansamitocin P-3 shows a potent cytotoxicity against the human solid tumor cell lines A-549 and HT-29. The compound exhibits a significant activity against P-388 lymphocytic leukemia in mice and both 9PS (murine lymphocytic leukemia) and 9KB (human nasopharyngeal carcinoma) in cell culture systems. [38]. 

The biosynthetic precursor of the chromophoric moiety was studied vigorously by several research groups. As a result it was established that during the biosynthesis of the ansamycins, a W-C7N unit (Fig. 4) was incorporated into the chromophores of both the benzenoid ansamycins, such as geldanamycin (85) [177, 178] and ansamitocin P-3 (81) [179], and also the naphthalenoid ansamycins, such as the rifamycins [22,180-182] and actamycin (69) [183]. 

Regarding the biosynthesis of the benzenoid ansamycin antibiotic ansamitocin P-3 (81), it was reported that the C-NMR signal of the benzyl carbon of ansamitocin was enhanced by feeding [1 -13C]-AHBA (118) [179]. 

A relatively recent paper by Mariani and Maffioli gives an excellent comparison of the various rifamycins and also leads into discussions of other ansamycin molecules including the geldanamycins and ansamitocins, both of which will be mentioned later. 

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