Benzenoid ansamycin antibiotics

Among the naphthalenoid and benzenoid ansamycin antibiotics, some ansamycins possess a 1,4-naphthoquinone or a 1,4-quinone unit as a chromophore, and others possess a 1,4-hydroxynaphthalene or a 1,4-hydroquinone units (or their derivatives) as a chromophore. Since these two types of chromphore are in most cases reversible, it is not appropriate to classify by the difference of the oxidation stage of the chromophore. In this review, benzenoid and naphthalenoid ansamycins are further divided according to the difference of the length of their ansa chains. Thus, naphthalenoid ansamycins are divided into 3 groups, i.e., naphthalenoid ansamycins with C17 ansa chains, naphthalenoid ansamycins with C23 ansa chains, and naphthalenoid ansamycins with C9 ansa chains. The benzenoid ansamycins are divided into 2 groups, i.e., benzenoid ansamycins with C15 ansa chains and benzenoid ansamycins with Ci7 ansa chains. The relationships between, and the antibiotics within these groups are indicated in Scheme 2. 

Benzenoid Ansamycin Antibiotics with Cis Ansa Chains... 

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]. 

As described in the introduction to this chapter, the chromophoric moiety of the benzenoid ansamycin antibiotics are biosynthetically derived from a "w-CyN unit" via the shikimate pathway, and the ansa chain moieties are derived from a "polyketide" chain via the condensation of acetate or glycolate (C2 unit) and propionate (C3 unit) moieties. 

Because the biosynthesis of the w-CyN unit was discussed previously, only the biosynthesis of the ansa moiety of the benzenoid ansamycin antibiotics with a C15 ansa moiety and the benzenoid ansamycin antibiotics with a C17 ansa moiety will be discussed here. 

Benzenoid Ansamycin Antibiotics with Cjs Ansa Moiety... 

Funayama et al. reported the possibility for the application of their model to the stereochemistry and biosynthesis of the Imown benzenoid ansamycin antibiotics [202]. According to the analysis, herbimycin A (86) seemed to possess the same biosynthetic building units as those of... 

In the benzenoid ansamycin antibiotics, the ansa chains of herbimycin A, geldanamycin, and macbecin I [7] are similar. It was shown that the ansa moiety of geldanamycin consisted of four molecules of propionic acid (P), two... 

Maytansine (73) was the first example of a benzenoid ansamycin with a Ci5 ansa chain. Maytansine was isolated originally from the higher plant Maytenus ovatus (Celastraceae). Subsequently, antibiotics related to maytansine were isolated from the fermentation broth of Nocardia sp. as well as other higher plants. Compounds belonging to the maytansinoid group possess a 1,3,5-trisubstituted benzene moiety as a chromophore. 

Other benzenoid ansamycins, geldanamycin [9,10] and herbimycin [11,12], are also known. Herbimycin was first isolated as a herbicidal antibiotic and was subsequently found to normalize tumor cells [13]. 

AnsamacroHdes. Antibiotics in the ansamacrolide family are also referred to as ansamycins. They are benzenoid or naphthalenoid aromatic compounds in which nonadjacent positions are bridged by an aliphatic chain to form a cyclic structure One of the aliphatic-aromatic junctions is always an amide bond, Rifampin is a semisynthetically derived member of this family and has clinical importance, it has selective antibacterial activity and inhibits RNA polymerase. 

Streptomyces hygroscopicus var. geldanus and shows antibiotic activity against protozoa [206]. From the same Streptomyces strain, AM-3672, herbimycin A (124) [207], B (125) [208] and C (126) have been isolated [209]. They exhibit herbicidal and antiviral activity and are able to reverse the characteristics of oncogene expression [120]. Herbimycin A (124) has been shown to have a potent antiangiogenic activity [211]. This latter biological activity distinguishes the benzoquinoid ansamycins from their benzenoid [212] and naphthoquinoid [213] ansamycin relatives. 

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