Fig. 1.

Isolation and chemical synthesis. (A) Structure of dinaphtho[2,3-b:2',3′-d]thiophene-5,7,12,13-tetraone or seriniquinone (1). Summary of salient NMR data including ¹H-¹H COSY (bold lines) and heteronuclear multiple-bond correlation spectroscopy correlations (arrows) observed in solutions of 1 in CDCl₃. (B) Images depicting the marine bacterium Serinicoccus sp. strain CNJ927 growing on a nutrient agar surface, and crystals of 1 (Inset). Culture broths of Serinicoccus sp., strain CNJ927, provided 0.067 mg/L of 1. (C) Repetition of the published synthesis of 1 (13) confirmed the structure of the natural product. Tetra-acetate hydroquinone 2 was prepared as a prodrug motif, which when absorbed in cells underwent acetate hydrolysis followed by oxidation to 1 (SI Appendix, Fig. S2). (D) Advance of synthetic methods permitted access to IAF probes 15 and 16, as well as derivatives 10, 12, 17, and 18. Reagents and conditions: (a) dithiooxamide, Et₃N, N,N-dimethylformamide (DMF), 50 °C, 10 h, 85%; (b) 30% aq. H₂O₂, AcOH, reflux, 3 h, 86%; (c) Zn dust, Ac₂O, reflux, 2 h, 67%; (d) NaOH, MeOH, 2 h; (e) CsCO₃, CH₃CN, rt, 72 h; (f) (ClCO)₂, DMF, CH₂Cl₂, 2 h, 49% (over 3 steps from 5); (g) Na₂S, aq. THF, rt, 1h; (h) K₂OsO₄ • 2 H₂O, N-methylmorpholine oxide, THF, H₂O, 16 h, 67% (over 2 steps from 8); (i) NaIO₄ on SiO₂, CH₂Cl₂, 2 h, 98%; (j) oxone, DMF, 2 h, 98%; (k) Zn dust, Ac₂O, reflux, 2 h, 65%; (l) 1-[bis(dimethylamino) methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU), EtNiPr₂, DMF, rt, 2 h, 29% for 16; (m) NaOMe, MeOH, 16 h, 24%; (n) tert-butyl acetidine-3-ylmethylcarbamate, HATU, EtNiPr₂, DMF, rt, 2 h, then TFA, CH₂Cl₂, 1 h, 42% (two steps). Starting material 5 was obtained as batch-dependent inseparable 5:2–6:1 mixture of 2-chloro-7-(4-methylpent-3-en-1-yl)naphthalene-1,4-dione (major) and 2-chloro-6-(4-methylpent-3-en-1-yl)naphthalene-1,4-dione (minor).