Asymmetric Synthesis and Absolute Configuration of Streptophenazine G

Abstract

The asymmetric synthesis of the antibacterial natural product, streptophenazine G, has been achieved by employing asymmetric alkylation and asymmetric aldol reactions using chiral oxazolidinones as the key steps. The originally proposed structure for streptophenazine G has been revised, and its absolute configuration has been determined to be 1'S,2'R,6'S. The asymmetric total synthesis of 6'-epi-streptophenazine G is also described.

Nature’s Lab for Derivatization: New and Revised Structures of a Variety of Streptophenazines Produced by a Sponge-Derived Streptomyces Strain

“…Structures of eight streptophenazines, produced by Streptomyces strain HB202, were described previously [10,11,12]. Figure 2 demonstrates the presence of almost 20 phenazines in extracts of this strain after fermentation in GYM4 medium.…”

“…Due to this fact, data were compared to those of Yang et al . [11,12], who clearly defined the core structure of streptophenazines A, B, E and G to be 1,6-disubstituted via total synthesis as well as X-ray crystallographic data (streptophenazine A). Based on the high similarity of the NMR data in addition to the assumption of a common biosynthesic pathway of the derivatives in the same Streptomyces strain HB202, 1,6-disubstitution of new streptophenazines could be determined.…”

“…Yang et al . [11,12] found that the like -configuration ( R , R or S , S ) in the very similar streptophenazines A or G had a coupling constant of 6.5 Hz, while the unlike -configuration ( R , S or the S , R ) had one of 7.5 Hz. The compounds 1 , 2 and 3 showed coupling constants of 7.7, 7.8 and 7.5 Hz, respectively, and thus should all have the unlike -configuration at C-1′ and C-2′.…”

“…For assignment of the absolute configuration, CD measurements were performed of streptophenazines I and K, and of (–)-streptophenazine G 9 whose absolute configuration was known from total synthesis [12]. Despite the presence of a large chromophore, all compounds surprisingly gave CD curves of very low intensity (Figure 5).…”

“…Eight derivatives of a new phenazine subgroup, the streptophenazines A–H, were isolated from cultures of this Streptomyces HB202 [10]. In part, the structures were revised later [11,12]. These streptophenazines have minor structural differences at positions C-1 and CH-2′, but exhibit important differences in their bioactivities.…”