Isolation, structural elucidation, biological properties, and biosynthesis of maleimycin, a new bicyclic maleimide antibiotic isolated from the culture filtrates of Streptomyces showdoensis. 14

Abstract

Maleimycin is a bicyclic maleimide antibiotic elaborated by Streptomyces showdoensis. The physical and chemical data show the structure for maleimycin to be 3aza-6-hydroxybicyclo[3.3.0]oct-Al iS-ene-2,4-dione. The nuclear magnetic resonance (nmr) spectra in DoO showed five welldefined resonances corresponding to the five nonexchangeable protons. The 13C spectra consisted of seven resonances: two resonances in the carbonyl region at -41.3 and -40.7 ppm, two resonances in the aromatic or unsaturated region at -29.3 and -23.7 ppm, and one resonance at +56.3 ppm During a study of showdomycin, a second ultraviolet absorbing compound was observed in the culture filtrates of Streptomyces showdoensis. This compound has been isolated and crystallized, and its physical and biological properties have been studied in much detail. By the use of H (proton) nuclear magnetic resonance (pmr) and 13C nmr (cmr), the resonances of the five nonexchangeable protons and the spectra of the seven carbons are described. It is now possible to report the structure of this new maleimide antibiotic as 3aza-6-hydroxybicyclo[3.3.0]oct-A15-ene-2,4-dione. The biochemical properties and biosynthesis are also described. Experimental ProcedureIsolation of Maleimycin. Cultures of S. showdoensis were grown for 42 hr as described by Elstner et al. (1973). The medium was filtered, passed through Dowex 50-X8 (H*) (20-50 mesh, 3 cm X 20 cm). The pH was adjusted to 4.5 (ammonium hydroxide), adsorbed on Norit A (10 g/L), and washed with 1 1. of water. Maleimycin was eluted batchwise with acetone-water (80:20, v/v) (three times, 500 ml each time). The eluent was concentrated under vacuum to 2 ml, spotted on four Whatman No. 3MM paper chromatograms t From the

Lugdunomycin, an Angucycline‐Derived Molecule with Unprecedented Chemical Architecture

“…Up-scale refermentation (20 L) of Streptomyces sp.QL37 in R5 medium followed by extensive systematic isolation, via OSMAC [8] identified compounds 2-45,i ncluding unrearranged benz[a]anthracene angucyclines (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), limamycins [17] ( [13][14][15][16][17][18][19], emycins [17][18][19] (20,21), naphthalenones (22, 23), anthraquinones (24, 25,F igure 1), nucleosides (26-33), cyclodipeptides (34-41), 4-quinolones (42, 43), vitamin K(44), and quinazolinone (45,S upporting Information, Figure S5). Of these,compounds 5, 9, 14-17,and 21-25 were new structures.…”

“…Of these,compounds 5, 9, 14-17,and 21-25 were new structures. The1 1n ew angucyclines featured, among others,u nique ring cleavage (ring AorC)and rearrangement (13-25), hydration of double bond D 12, 12a (15,16), nucleophilic addition of methanol to the ketone at C-7 (14), epoxidation of double bond D 6a, 12b (5), Nquaternary methylation (16), amidation (13-19, 24,a nd 25), and reduction of the ketone at C-7 (20,21). The1 1n ew angucyclines featured, among others,u nique ring cleavage (ring AorC)and rearrangement (13-25), hydration of double bond D 12, 12a (15,16), nucleophilic addition of methanol to the ketone at C-7 (14), epoxidation of double bond D 6a, 12b (5), Nquaternary methylation (16), amidation (13-19, 24,a nd 25), and reduction of the ketone at C-7 (20,21).…”

Glutathione-Dependent Conversion of N -Ethylmaleimide to the Maleamic Acid by Escherichia coli : an Intracellular Detoxification Process

“…3c). The structural assignment 6 : nH ϭ number of protons, where n is a number between 1 and 5; the chemical shift (␦) is shown in ppm; s ϭ singlet, d ϭ doublet, t ϭ triplet, q ϭ quartet, m ϭ multiplet of peaks on the NMR spectrum, and J (Hz) is the coupling constant between these peaks.…”

“…1a); at 10 to 15 M NEM, approximately t 1/2 ϭ 30 s (n ϭ 6) was required for formation, whereas the breakdown was relatively slow (t 1/2 ϭ 15 Ϯ 3 min [n ϭ 6]). Although NEM is a man-made compound, there are a number of natural products with structures related to the maleimide ring, e.g., showdomycin, pencolide, and maleimycin (3,6), that are produced by bacteria and fungi. Such compounds may be detoxified by the formation of GSH adducts.…”

Antibacterial Activity of 3-Substituted Pyrrole-2,5-diones Against Pseudomonas Aeruginosa

“…Using a moderate excess of amides in presence of a catalytic amount of sulphuric acid, mucohalogen acids were reacted with simple alkyl-amides to give in a one pot reaction, 3-halogenated-Nalkyl-pyrrole-2,5-diones. Structurally similar pyrrole based antibiotics were isolated from streptomycedes showdoensis [21]. We would like to stress that our synthesis is the only available laboratory synthesis of halogenated N-alkylpyrrole-2,5-diones.…”