Antibiotic Carbazoles

In addition to these carbazole alkaloids, isomers of glycozoline and giiinimbine were tested against various microbes and found to be active against S. aureus (446). Some aminoacyl carbazoles were found to be active against B. subtilis (ICC-Strain) and B. cereus (NRRL-B-569) (447). 

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In 1993, Oki et al. isolated the novel carbazole antibiotics epocarbazolin A (258) and B (259) from the culture broth of Streptomyces anulatus T688-8 (230). They represent the first carbazole alkaloids with an epoxide moiety in a side chain, and are the epoxides corresponding to carbazomadurin A (256) and B (257). Epocarbazolin A (258) [oC + 75.0 (c 0.5, MeOH) and B (259) Mg -b 78.0 (c 0.5, MeOH) were obtained from Nature in optically active form. However, their absolute configuration is not known. These alkaloids showed potent 5-lipoxygenase inhibitory activity and weak antibacterial activity (230) (Scheme 2.63). 

Enol and thioenol ethers have been used as starting materials in a Diels-Alder reaction used as a key step for the synthesis of carbazo-mycins, which are newer carbazole alkaloids with antibiotic activity (87H325, 87TL3079 89CPB1999 92C441). 

Carbazomycins A and B, isolated from an unidentified Streptomyces species, prove to be the first known antibiotics that contain a carbazole skeleton. Carbazomycin B is 4-hydroxy-3-methoxy-l,2-dimethylcarbazole and carbazo-mycin A is its 0-methyl ether.5 ... 

Many aromatic systems have been oxidized by Fremy s salt, including phenols, naphthols, anilines, quinolines, indoles, carbazoles, and polyaromatic systems. The review articles by Zimmer and Parker can be consulted for specific examples. Slight modifications of the mechanism presented in Scheme 20 explain the oxidation of most of these classes of compounds [63], Oxidations by Fremy s salt and related nitroxides have been used in the total synthesis of several biologically active compounds [64], Recent examples can be found in the syntheses of the antitumor antibiotic streptonigrone (34), the antitumor agent EO-9 (35), the anti-rheumatic agent epoxyquinomicin B (36), and the antineoplastic agent makaluvamine C (37) (Scheme 21) [65]. 

In other miscellaneous indole alkaloid syntheses. Joule reported formal syntheses of the makaluvamines <97JOC568> while Lown has developed a new synthesis of the pyrroloquinone nucleus of these alkaloids <97SC2103>. Edstrom reported the synthesis of a fully functionalized 7-aminoaziridinomitosene <97T4549>, and two new approaches to the duocarmycins were reported <97JOC8868,97TL7207>. Finally, Knolker has utilized his iron-mediated construction of carbazoles in the first. synthesis of the antibiotic carbazomycins C and D <97JCS(P1)349>, as well as other carbazole natural products. 

Carbazomycins. The carbazole alkaloids C. A-H are isolated from cultures of Streptoverticillium ehimense (syn. S. abikoense), e.g. C. A C,6H,7N02, Mr 255.31, yellow needles, mp. 143-146 °C. C. are antibiotics and interesting synthetic targets. 

Kinamydno. A family of antibiotics from streptomy-cetes with activity against Gram-positive bacteria, however, their use is limited by their high toxicity. At first, an /V-cyanobenzo[b]carbazole structure was... 

Plants from the Rutaceae have been used in folk medicine in the treatment of eczema, rheumatism, stomachache, dysentery, herpes etc. 29 presently, none of these effects have been correlated to any carbazole alkaloid. Some Rutaceae carbazole alkaloids have however been screened for antibiotic activity, and cytotoxic activity has been found for koenoline (Figure l).i 20... 

The hyellazoles (3) isolated from the blue green alga Hyella caespltosa, and the carbazomycins (4) produced by the actinomycete Streptoverticillium ehimense, show a substituent pattern different from the Rutaceae carbazole alkaloids They all share the common features of carbon substituents in the 1 and 2-positions, and an oxygen functionality in the 3-position. Antibiotic activity is reported for carbazomycin B (4b).32... 

The kinamycins (6), antibiotics produced by Streptomyces murayamaensis, are composed of a partially reduced carbazole nucleus.A purple compound isolated in small quantities from the same species is believed to have the structure 7 on basis of spectroscopic data. Compounds similar to 7 are proposed as biosynthetic precursors of the kinamycins. 3 ... 

J 1-Dihydro-l J-dihydroxy-3-methyl-6,l l-dioxo-5H-benzo[b carbazole-5-carbonitrile, 9CI. Antibiotic PI [120796-24-9]... 

Nagappan, T.. Ramasamy, P., Wahid, M. E., Segaran, T. C., and Vairappan, C. S. (2011). Biological activity of carbazole alkaloids and essential oil of Murraya koenigii against antibiotic resistant microbes and cancer cell lines. 16,9651-9664. 

Knolker, H., and M. Bauermeister The Total Synthesis of Carbazole Antibiotic... 

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