Rifamycine-type ansamycine antibiotic

Kanglemycin A (18) was isolated from the culture broth of Nocardia mediterranei var. kanglensis 1747-64. Kanglemycin A (18) is one of the rifamycin-type ansamycin antibiotics which possesses inhibitory activity against Gram-positive bacteria [68]. 

A reiterative application of a two-carbon elongation reaction of a chiral carbonyl compound (Homer-Emmonds reaction), reduction (DIBAL) of the obtained trans unsaturated ester, asymmetric epoxidation (SAE or MCPBA) of the resulting allylic alcohol, and then C-2 regioselective addition of a cuprate (Me2CuLi) to the corresponding chiral epoxy alcohol has been utilized for the construction of the polypropionate-derived chain ]R-CH(Me)CH(OH)CH(Me)-R ], present as a partial structure in important natural products such as polyether, ansamycin, or macro-lide antibiotics [52]. A seminal application of this procedure is offered by Kishi s synthesis of the C19-C26 polyketide-type aliphatic segment of rifamycin S, starting from aldehyde 105 (Scheme 8.29) [53]. 

Thus, the three ansamycins whose biosyntheses have been investigated are derived from closely related biosynthetic pathways. The streptovaricin and rifamycin ansa chains are derived from seven propionate and two acetate (malonate) units, the geldanamycin ansa chain from four propionate, one malonate and two still unidentified 2-carbon units. In two of the three antibiotics (and presumably in streptovaricin as well) a C7N unit is derived from glucose via a shikimate-type pathway. Although a number of late intermediates in the biosynthesis of rifamycin and streptovaricins have been identified, much remains to be done. 

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