Identification of Prekinamycin in Extracts of Streptomyces murayamaensis

The Journal of Organic Chemistry
1996.0

Abstract

The kinamycin antibiotics, first isolated from Streptomyces murayamaensis, were originally reported as N-cyanobenzo[b]carbazoles. One metabolite ("Cpd A") was named prekinamycin as it lacked the oxidative elaboration of one ring, but its synthesized structure did not match Cpd A. Subsequently, the structures of kinamycins were revised to 5-diazobenzo[b]fluorenes (e.g., prekinamycin 1 and kinamycin D 2). Intermediates 3 (kinoscurinone) and 4 (stealthin C) in kinamycin biosynthesis were synthesized and demonstrated. Attempts to synthesize prekinamycin from tetramethyl benzo[b]fluorenone 5 yielded unexpected products. Synthetic 1 was found to match another S. murayamaensis metabolite ("Cpd B") instead of Cpd A, confirmed by HPLC, UV/vis spectrum, and 1H NMR. Cpd B, present in extracts of S. murayamaensis mutant MC2 (grown in 7% farina-based medium at 28 °C) and wild strain (grown in galactose/asparagine-based medium at 35 °C), was identified as prekinamycin (structure 1), while Cpd A's structure remains unclear. Future efforts will test its intermediacy in kinamycin biosynthesis.

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