Rifamycin absolute configuration

The structures of rifamycins B and S have been vigorously studied and finally the structure of rifamycin B (1) (as a />-iodoanilide) was determined by X-ray crystallographic analysis [38,39] and the configurations of 1 and related compounds were described [28,40]. As described above, the absolute configuration of 1 was investigated by X-ray crystallography, and it was defined with no mirror image problem [38,39,41,42]. 

Subsequently, the halomicins A (9), B (10) and C (11) were purified from the antibiotic complex and their structures determined. The structure of halomicin B (10) was quite similar to that of the rifamycin group, except that it possessed a pyrrolidine moiety at the C-4 position of the chromophore, and 10 possessed the same ansa moiety as some of the rifamycin group of antibiotics. In fact, the absolute configuration of the ansa moiety of 10 was determined by transforming rifamycin O (7) into 10 [62, 63]. 

Funayama et al. suggested the possibility of the application of this model for the determination of the stereochemistry and biosynthetic pathway of the known ansamycin antibiotics [202]. According to this proposal, it is important to consider that, of the C17 ansa chain naphthalenoid ansamycins, the absolute configurations of rifamycins S (2) [16, 194] and B (1) [33, 42], and streptovaricin C (44) [94], were established by X-ray analysis. The rigorous biosynthetic studies of rifamycin S (2) indicated P-A-P-P-P-P-P-P-A-P as the biosynthetic sequence of the ansa chain and a part of the naphthalenoid moiety [197]. 

This can be estimated to be common pathway to rifamycin B (1) and streptovaricin C (44). In addition to their biogenesis, the absolute configuration of these compounds can be speculated to be the same as each other, except for the configurations at the C-6 and C-7 positions (Fig, 11). Taking into consideration the configurational models tentatively established herein, the configuration of awamycin (26) was estimated to be as shown in the structure. 

It was also shown that the absolute configuration between C-8 and C-16 of rifamycin B [4] and streptovaricin C [5] are the same. In addition, a methyl moiety derived from a propionic acid unit attached to the Cl moiety of the m-CyN unit corresponds to the methyl moiety at the C-20 position of the naphthalenoid chromophore. In all of these alkaloids, an oxygen atom derived from propionic acid remains at the C-19 position. This information can be applied to the elucidation of the chemical structure and stereochemistry of various naphthalenoid ansamycins, for example awamycin, which belongs to naphthalenoid ansamycins [6]. 

---