Tepuazines A-E: Phenazine Glycosides from a Venezuelan Quartz-Rich (Tepui) Cave Soil-Derived Streptomyces virginiae CMB-CA091.

Investigation of the secondary metabolites of Streptomyces virginiae CMB-CA091 isolated from the quartz-rich (tepui) soil of a cave in Venezuela yielded two new dimeric phenazine glycosides, tepuazines A and B ( 1 and 2 ); three new monomeric phenazine glycosides, tepuazines C-E ( 3 - 5 ); and a series of known analogues, baraphenazine G ( 6 ), phenazinolin D ( 7 ), izumiphenazine C ( 8 ), 4-methylaminobenzoyl-l-rhamnopyranoside ( 9 ), and 2-acetamidophenol ( 10 ). Structures were assigned to 1 - 10 on the basis of detailed spectroscopic analysis and biosynthetic considerations, with 1 and 2 featuring a rare 2-oxabicyclo[3.3.1]nonane-like ring C/D bridge shared with only a handful of known Streptomyces natural products. We propose a plausible convergent biosynthetic relationship linking all known members of this structure class that provides a rationale for the observed ring C/D configuration.