104 人人人人人 111 CH-OH 405 pyridine streptok the kno human cancer cell lines(ICmL-)but did not exhibit actiiFeTentation amycin metabolite,Y-indomycinone(113).along with the kno from terrestrial Streptomyces spp. HO same group identif nove CH with the known ketodiol guaymasone.from a second Baci 112 streptokordin 113y-indomycinone ent s sp. a unique [4.2.2]ring system,accompanied by six known compounds." ucture and relative stereochemistry of the abyssomicins was NH acdrydofolae biosynthetic pathwaydn ctivity towards Gram-positive bacteria. CH HN HN- 110 chloro-dibydr oquinones U719 with IC values of 240 and ton Fracture Zone.yielded a novel cyclic tetrapeptide.cyclo(L 0.97ugmLfor 117 and 118 respectively,against human HCT olon carcinom along with cant cytotoxicity,the purified metabolite was inactive. antibacteril activity owards This joumal isThe Royal Society of Chemistry 2008 Nat.Prod.Rep,2008,25,1131-1166|114
cyclic acylpeptide halobacillin (107), a member of the iturin class of natural products,165 while the same group identified two novel aromatic triols, guaymasol (108) and epiguaymasol (109), along with the known ketodiol guaymasone, from a second Bacillus sediment species obtained by drilling at 1834 m in the Guaymas Basin.166 A further Pacific sediment Bacillus sp. (5059 m depth) yielded the novel cytotoxic phenazine derivative (110) with a unique [4,2,2] ring system, accompanied by six known compounds.167 The culture broth of a Nocardiopsis sp. actinomycete obtained from 3000 m deep, benthic sediment from the Clarion–Clipperton Fracture Zone, yielded a novel cyclic tetrapeptide, cyclo(Lisoleucyl-L-prolyl-L-leucyl-L-prolyl) (111), along with several diketopiperazines.168 Although the crude extract showed signifi- cant cytotoxicity, the purified metabolite was inactive. The culture broth of an actinomycete strain belonging to the Streptomyces genus collected from deep-sea sediment at Ayu Trough, Pacific Ocean, was found to contain the novel methylpyridine streptokordin (112), along with the known compounds nonactic acid, dilactone, trilactone, and nonactin.169 Streptokordin (112) displayed significant cytotoxicity against seven human cancer cell lines (IC50 <10 mg mL1 ) but did not exhibit antibacterial or antifungal activity. Fermentation of another Streptomyces sp. obtained from a 4680 m deep sediment core off the coast of Majuro, Marshall Islands, provided a new pluramycin metabolite, g-indomycinone (113), along with the known metabolites rubiflavinone C-1 and b-indomycinone.170 The pluramycin class of antibiotics had only previously been isolated from terrestrial Streptomyces spp. An actinomycete, Verrucosispora sp., obtained at a depth of 289 m in the Sea of Japan, was found to contain the unique polycyclic antibiotics, the abyssomicins B–D 114–116. 171 The structure and relative stereochemistry of the abyssomicins was confirmed by X-ray crystallography, and the absolute stereochemistry deduced using the Mosher and Helmchen method. Abyssomicin C (116) was found to inhibit the para-aminobenzoic acid/tetrahydrofolate biosynthetic pathway, and exhibited strong activity towards Gram-positive bacteria.172 A new genus of actinomycete isolated from 152 m deep-sea sediment (La Jolla, California) has furnished the cytotoxic chloro-dihydroquinones 117–119, with IC50 values of 2.40 and 0.97 mg mL1 for 117 and 118 respectively, against human HCT- 116 colon carcinoma cells, along with two known chlorinated dihydroquinones.173–175 The compounds also displayed potent antibacterial activity towards vancomycin-resistant Enterococcus This journal is ª The Royal Society of Chemistry 2008 Nat. Prod. Rep., 2008, 25, 1131–1166 | 1141
123 R:=B-glucosyl.R2=H 124R,=H,R2=B-gu0o03y 125 macrolactin D 119 2 and B 126 macrolactin E 12716,17 broth of an unidentified gram-positive bacterium obtained from 5065m sediment from the Central Pacific Basin.the The H 1915-ket-16.17-dihydro P simplex virus-II (HSV-ID). rate antivira HO OH isomacrolactinic acid mR:人入入 HO 121R=入 The antimicrobial macrolactins A-F(122-127).along with 语a切 Fungi The deep-sca fungus Aspergillus sydowi.obtained at a depth of 1000 m,was fo 0 =0 meta with latte H0- 深 132 133 134 isolated from the same sample. he cytotoxic pen (135)anc uture broth of ae-erived leista sp.iso one B (I known ans s A and B.wer from the same sample. between Fiii and Matuka." 1142|Nat.Prod.Rep,.2008,25,1131-1166 This journal isThe Royal Society of Chemistry008
faecium (VREF), and methicillin-resistant Staphylococcus aureus (MRSA) with MIC values ranging from 1.95–15.6 mg mL1 . Two new cytotoxic caprolactams, caprolactins A (120) and B (121), were isolated as an inseparable mixture from the culture broth of an unidentified Gram-positive bacterium obtained from 5065 m deep ocean sediment from the Central Pacific Basin, the deepest reported sample from which a new natural product has been isolated.176 The structure of the caprolactins has been confirmed by synthesis, and both exhibit significant cytotoxicity against human KB (epidermal) and LoVo (colorectal) tumour cell lines, as well as moderate antiviral activity against Herpes simplex virus-II (HSV-II). The antimicrobial macrolactins A–F (122–127), along with macrolactinic acid (128) and isomacrolactinic acid (129), were isolated from an unclassifiable deep-sea bacterium obtained from a 980 m deep sediment sample from the North Pacific.177 The macrolactins have been elegantly reviewed by Baker et al.37 Fungi The deep-sea fungus Aspergillus sydowi, obtained at a depth of 1000 m, was found to produce two novel pyranone (130) and chromenone (131) metabolites, with the latter compound exhibiting significant cytotoxicity towards the murine P388 cell line (IC50 0.14 mM).178 Six known natural products were also isolated from the same sample. Three new compounds, p-hydroxyphenopyrrozin (132) and the diketopiperazines (133–134), have been obtained from the culture broth of a marine-derived fungus Chromocleista sp. isolated from 70 m deep sediment from the Gulf of Mexico.179 Other known natural products, including phenopyrrozin, four diketopiperazines, N-acetyltryptamine and agathic acid, were obtained from the same sample. The cytotoxic pentaketides (+)-formylanserinone B (135) and ()-epoxyserinone A (136) (and its enantiomer) along with minor amounts of hydroxymethylanserinone B (137) and deoxyanserinone B (138) and the known anserinones A and B, were isolated from a salt-water culture of two Penicillium corylophilum fungal strains obtained from a 1335 m deep sediment grab between Fiji and Matuka.180–182 1142 | Nat. Prod. Rep., 2008, 25, 1131–1166 This journal is ª The Royal Society of Chemistry 2008