Isolation from Streptomyces

M.p. 296 C. Accepts an electron from suitable donors forming a radical anion. Used for colorimetric determination of free radical precursors, replacement of Mn02 in aluminium solid electrolytic capacitors, construction of heat-sensitive resistors and ion-specific electrodes and for inducing radical polymerizations. The charge transfer complexes it forms with certain donors behave electrically like metals with anisotropic conductivity. Like tetracyanoethylene it belongs to a class of compounds called rr-acids. tetracyclines An important group of antibiotics isolated from Streptomyces spp., having structures based on a naphthacene skeleton. Tetracycline, the parent compound, has the structure ... 

Naphthoquiaomycias A (67) and B (68) are isolated from Streptomyces S-1998 (223) and the stmctures for (67) and (68) assigned on the basis of spectral data. Naphthoquiaomycias A and B inhibit fatty acid synthesis ia E. coli. Actamycia (69) is obtaiaed from Streptomyces sp. EJ784 and its stmcture arrived at on the basis of spectral data and degradation studies (224,225). 

Three more antibiotics, all discovered about 1953, are also derivatives of cytosine. Amicetin, bamicetin and plicacetin may all be isolated from Streptomyces plicatus and all have some activity against some acid-fast and Gram-positive bacteria as well as some other microbial systems (69MI21301). Structural work in this area is fascinating (62JOC2991). 

There has been one report on the biosynthesis of FR900482 [114]. Radiolabeled D-glucosamine 33 and AHBA 38 were efficiently incorporated into 6, and D-[l-13C]-glucosamine was incorporated in the expected orientation (Figure 11.10). The biosynthetic gene cluster for FR900482 has been isolated from Streptomyces sandaensis and indicates a strong biosynthetic relationship with mitomycin C (Y. Mao, D. H. Sherman, unpublished results). 

Compound 593A (109 Scheme 11.16) was isolated from Streptomyces griseoluteus by a group at Merck, Sharp, and Dohme in 1970 [167]. Its structure was proposed in 1973 [168] and confirmed by X-ray crystallography in 1976 [169, 170], The trivial name streptolutine was proposed for the amino acid 110, so 109 would conse-... 

The anthracyclines represent a broad family of antibiotics that exhibit activity in numerous tumors. The first anthracyclines, doxorubicin (DOX) and dau-notubicin (DNR), were isolated from Streptomyces var peucetius they were shown to be composed of a tetracyclic ring system with adjacent quinone-hydro-quinone moieties, a short side chain with a carbonyl group, and an aminosugar bound to the C-7 of the four-ring system. DOX and DNR only differed in the side chain terminus (-CH2OH in DOX vs. -CH3 in DNR). Second generation anthracyclines, like epitubicin (EPI) and idatubicin (IDA), were obtained after minor chemical modifications of DOX or DNR, respectively (Fig- 1). 

The desymmetrization principle was also exploited in the synthesis of (+)-FR900482, an antitumor antibiotic isolated from Streptomyces sandaensis [155]. A prochiral propanediol was enzymatically desymmetrized using PSL to give the corresponding (S)-monoester as illustrated in Figure 6.59. 

The first compound is an antibiotic isolated from Streptomyces aureus [20], while the second compound is a cytotoxic antibiotic isolated from Dysidea fragilis, a marine sponge [21]. A logical approach to the synthesis of azirines would be an elimination reaction of a suitably M-substituted aziridine. Thus, AT-chlorination of aziridine-2-carboxylic esters was carried out using ferf-butyl hypochlorite (Scheme 8). 

Teleocidin isolated from Streptomyces mediocidicus is a mixture of two isomers of teleocidin A and four isomers of teleocidin B (Figure 1 and Table I) (11,12). (-)-Indolactam-V is a biosynthetic intermediate of teleocidins A and B (7J). Des-O-methylolivoretin C is a regioisomer of teleocidin B-1 (Table I) (14). 

Figure 7.23 shows the prototype diazobenzo[Z ]fluorene-based natural products kinamycin A and prekinamycin. The kinamycin A-D family were first isolated from Streptomyces murayamaensis, but the structures were incorrectly characterized as having a cyanobenzo[Z ]carbazole ring. Since the initial discovery of the kinamycins, many new analogues have been discovered from natural sources.88-92... 

Combining, in tandem, the nitro-aldol reaction with the Michael addition using thiophenol is a good method for the preparation of P-nitro sulfides as shown in Eqs. 4.2 and 4.3. This reaction is applied to a total synthesis of tuberine. Tuberine is a simple enamide isolated from Streptomyces amakusaensis and has some structural resemblance to erbastatin, an enamide which has received much attention in recent years as an inhibitor of tyrosine-specific kinases. The reaction of p-anisaldehyde and nitromethane in the presence of thiophenol yields the requisite P-nitro sulfide, which is converted into tuberine via reduction, formylation, oxidation, and thermal elimination of... 

Pyrrolostatin is a novel lipid peroxidation inhibitor, which is isolated from Streptomyces chrestomyceticus. Its structure consists of a pyrrole-2-carboxylic acid with a geranyl group at the 4-position. It is readily prepared by applying the Barton-Zard pyrrole synthesis, as shown inEq. 10.23.24... 

There are several naturally occurring variations on the lactam-thiazolidine or lactam-dihydrothiazine structures, leading to other useful antibiotics or to inhibitors of the (5-lactamases, enzymes that hydrolyze the (5-lactam unit. One group, termed carbapenems 5 has a five-membered ring in which the thiazolidine sulfur is replaced with CH2- Such compounds may still contain sulfur in a thioethylamine side chain (derived from L-cysteine) as in thienamycin 6, originally isolated from Streptomyces cattleya (Scheme 2). 

Mycothiol 43 (Scheme 14) is a complex cysteine derivative isolated from Streptomyces clavuligerus, Mycobacterium bovis, and other mycobacteria. It... 

Rochet and Lancelin50 reported revised 1H and 13C NMR assignments of the polyene antibiotic Filipin m (83). This macrolide which was isolated from Streptomyces filipinensis was reinvestigated in DMSO-dg solution using homonuclear and heteronuclear correlation spectroscopy. In addition to several corrections to previous 1H NMR... 

Tetracyclines are a group of antibiotics derived from bacteria. Chlortet-racycline was isolated from Streptomyces aureofaciens and oxytetracycline from Streptomyces rimosus. Tetracychnes act by binding to receptors on the bacterial ribosome and inhibit bacterial protein synthesis. 

Much more exciting biologic properties have been revealed for the equally 1,6-disubstituted phenazoviridin (56) isolated from Streptomyces sp. HR04. The new free radical scavenger showed strong in vitro inhibitory activity against lipid peroxidation and displayed in vivo antihypoxic activity in mice [57]. 

C (81) isolated from Streptomyces sp. 833 [75-77] as neuronal cell protecting substances. The stereochemistry of these compounds remains to be established. 

In contrast to the 1- and 2-oxygenated tricyclic carbazole alkaloids, most of the 3-oxygenated and the 3,4-dioxygenated tricyclic carbazole alkaloids were isolated from Streptomyces (Scheme 2). Their common structural feature is a 2-methylcarbazole, although biosynthetic studies on carbazomycin B have shown that tryptophan is the precursor of the carbazole nucleus [26]. 4-De-... 

Isolated from Streptomyces Amino acid with antimicrobial activity 90 catenulae (inhibitor of alanine racemase)... 

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