Phytochemical studies on Stemona aphylla: isolation of a new stemofoline alkaloid and six new stemofurans

A new stemofoline alkaloid, (2'S)-hydroxy-(11S,12R)-dihydrostemofoline (3), new stemofurans M-R (8-13), and known compounds stemofoline (1), (2'S)-hydroxystemofoline (2), stemofuran E (4), stemofuran F (5), stemofuran J (6), and stilbostemin F (7) have been isolated from the root extracts of Stemona aphylla. The structures and relative configurations of these new compounds have been determined by spectroscopic data interpretation and from semisynthetic studies. These natural and semisynthetic alkaloids were tested for acetylcholinesterase inhibitory activities and were found to be 10-20 times less active than 1',2'-didehydrostemofoline itself. Stemofurans 4, 6, 8, 11, and 13 were tested for their antibacterial and antifungal activities. Three of these showed antibacterial activities against MRSA with MIC values of 15.6 μg/mL.     

Verticillane derivatives from Bursera suntui and Bursera kerberi

The stems of Bursera suntui afforded two new verticillane derivatives, (1S,3Z,7E,11S,12S)-(+)-verticilla-3,7-dien-12,20-diol (1) and (1S,3Z,7E,11S,12S)-(+)-verticilla-3,7-dien-12,20-diol 20-acetate (2), together with (1S,3E,7E,11R)-(+)-verticilla-3,7,12(18)-triene (3), (1R,3E,7E,11R,12Z)-(+)-verticilla-3,7,12-triene (4), (1R,7E,11Z)-(-)-verticilla-4(20),7,11-triene (5), and (1S,3E,7E,11S,12S)-(+)-verticilla-3,7-dien-12-ol (6). Compounds 3 and 4 are new enantiomerically pure natural products whose racemic mixtures, derived from synthetic approaches toward the taxane skeleton, were obtained previously. The stems of Bursera kerberi afforded the new (1S,3E,7E,11S,12R)-(+)-verticilla-3,7-dien-12-ol (7) together with 3-5. This is the first time that verticillane derivatives have been isolated from the genus Bursera. Their structures and stereochemistry were elucidated by 1D and 2D NMR data, including COSY, NOESY, HSQC, and HMBC experiments, while the absolute configuration was determined by comparison of the optical rotatory dispersion data with that of recently revised (1S,3E,7E,11S,12S)-(+)-verticilla-3,7-dien-12-ol (6), obtained from Sciadopitys verticillata, and those of (1R,3E,7E,11R,12R)-(-)-verticilla-3,7-dien-12-ol (8) and (1R,3E,7E,11R,12S)-(-)-verticilla-3,7-dien-12-ol (9), isolated from the liverwort Jackiella javanica. The conformational preferences of 1-7 were studied by molecular mechanics modeling employing the Monte Carlo protocol.     

Sesquiterpene lactones from Lychnophora ericoides

Two new sesquiterpene lactones, (4S,6R,7S,8S,10R,11S,16R)-1-oxo-3(10),8(16)-diepoxy-16-methylprop-1Z-enyl-16-methoxygermacra-2-en-6(12)-olide (1) and (4S,6R,7S,8S,10R,11S)-1-oxo-3,10-epoxy-8-angeloyloxygermacra-2-en-6(12)-olide (2), were isolated from Lychnophora ericoides. Their structures, including absolute configuration, were established by spectroscopic methods, including single-crystal X-ray analysis. Monitoring the furanoheliangolide metabolism of L. ericoides revealed an increase in biosynthesis during the plant flowering period.     

An approach to furolabdanes and their photooxidation derivatives from R-(+)-sclareolide

A synthetic route to furolabdanes from commercially available R-(+)-sclareolide is reported, with the specific aim of preparing (12R and 12S,15xi)-12,15-dihydroxylabda-7,13-dien-16,15-olides (3 and 5) and (12R and 12S,16xi)-12,16-dihydroxylabda-7,13-dien-15,16-olides (4 and 6). The key points of our approach are the use of Weinreb's amide 11 to join the furan ring to the terpenic unit. Photooxidation of the furan moiety of compounds 15 and 16, and of their acetates 19 and 20, has been used to built the hydroxybutenolide fragment. In this way the four possible isomers at the butenolide moiety, compounds 3-6, and their C-12 acetyl derivatives 21-24 have been obtained. On the basis of comparison of the spectral data ((1)H NMR) of the synthetic peracetates 25-28 (derived from 21-24) with the reported data for the peracetate 2 (derived from the natural product 1), the relative configuration at carbon C-12 of the natural product has been corrected. Furthermore, the absolute configuration of the natural product 1, considered to belong to the enantio-series, has to be changed to the normal-series on the basis of the optical rotation obtained for the synthetic derivative.     

Cytotoxic dolabellane diterpenes from the Formosan soft coral Clavularia inflata

Six new cytotoxic dolabellane diterpenes, (1R,12R)-dolabella-4(16),7,10-triene-3,13-dione (1), (1R*,7R*,8S*,12R*)-dolabella-4(16),10-diene-7,8-epoxy- 3,13-dione (2), (1R*,10R*,11S*,12R*)-dolabella-4(16),7-diene-10,11-epoxy-3,13-dione (3), (1R)-dolabella-4(16),7,11(12)-triene-3,13-dione (4), (1R*,3R*)-3-hydroxydolabella-4(16),7,11(12)-triene-3,13-dione (5), and (1R*,7R*)-7-hydroperoxydolabella-4(16),8(17),11(12)-triene-3,13-dione (6), have been isolated from the Formosan soft coral Clavularia inflata. The structures of compounds 1-6 were determined by 1D and 2D spectral analysis, and their cytotoxicity against selected cancer cells was measured in vitro.     

Terpene isocyanides, isocyanates, and isothiocyanates from the Okinawan marine sponge Stylissa sp

Seven new nitrogenous terpenoids, (1R,6R,7S,10S)-10-isothiocyanatocadin-4-ene (1), (1S,2S,5S,6S,7R,8S)-13-isothiocyanatocubebane (2), (1R,3S,4R,7S,8S,12S,13S)-7-isocyanoamphilecta-10,14-diene (3), (1S,3S,4R,7S,8S,12S,13S)-8-isocyanoamphilecta-11(20),14-diene (4), (3S,4R,7S,8S,11S,13S)-8-isocyanoamphilecta-1(12),14-diene (5), 8-isocyanatocycloamphilect-10-ene (6), and 8-isothiocyanatocycloamphilect-10-ene (7), were isolated from the Okinawan sponge Stylissasp., along with 12 known related compounds. Structural determinations of these compounds were made by spectroscopic analysis, and assessment was made of their cytotoxicity toward HeLa cells.     

Cembrane diterpenes from the southern African soft coral Cladiella kashmani

Two known cembrane diterpenes, flaccidoxide (1) and (1Z,3E,7E,11S, 12S,14S)-11,12-epoxy cembra-1,3,7-trien-14-ol (2), and the new cembrane diterpene flaccidoxide-13-acetate (3) were isolated from specimens of Cladiella kashmani collected off Ponto do Oura, Mozambique. The modified Mosher's method established the previously unassigned absolute configuration of 1 as (1Z,3E,7E,11S,12S,13S, 14R)-14-acetoxy-11,12-epoxy cembra-1,3,7-trien-13-ol. Acetylation of 1 yielded 3 and thus confirmed the structure of 3 as (1Z,3E,7E,11S, 12R,13S,14R)-13,14-diacetoxy-11,12-epoxy cembra-1,3,7-triene. All three diterpenes were toxic to the brine shrimp Artemia salina.     

Oxygenated pimarane diterpenes from Kaempferia marginata

Six new diterpenes, (1R,2S,5S,7S,9R,10S,13R)-1,2,7-trihydroxypimara-8(14),15-diene (1), (1R,2S,5S,9S,10S,11R,13R)-1,2,11-trihydroxypimara-8(14),15-diene (2), (1S,5S,7R,9R,10S,11R,13R)-1,7,11-trihydroxypimara-8(14),15-diene (3), (1S,5S,9S,10S,11R,13R)-1,11-dihydroxypimara-8(14),15-diene (4), (5S, 6R,9S,10S,13R)-6-hydroxypimara-8(14),15-diene-1-one (5), and (1R,2S,5S,7S,9R,10S,13R)-1,2-dihydroxypimara-8(14),15-diene-7-one (6), along with four known diterpenes, have been isolated from the dichloromethane extract of whole plants of Kaempferia marginata. The structures were assigned by spectroscopic methods. The absolute configuration of 1 was established by the Mosher ester method. Substances obtained were evaluated against a panel of bioassays including antimalarial, antituberculous, and antifungal activity.     

New peroxy triterpenes from the aerial roots of Ficus microcarpa

Six new triterpenes, 3 beta-acetoxy-12 beta,13 beta-epoxy-11 alpha-hydroperoxyursane (1), 3 beta-acetoxy-11 alpha-hydroperoxy-13 alpha H-ursan-12-one (2), 3 beta-acetoxy-1 beta,11 alpha-epidioxy-12-ursene (3), (20S)-3 beta-acetoxylupan-29-oic acid (4), (20S)-3 beta-acetoxy-20-hydroperoxy-30-norlupane (5), and 3 beta-acetoxy-18 alpha-hydroperoxy-12-oleanen-11-one (6), together with 3 beta-acetoxy-12-oleanen-11-one (7), were isolated from the aerial roots of Ficus microcarpa. Compounds 1-3, 5, and 6 were characterized as new peroxytriterpenes. The structures of 3 and 6 were confirmed by X-ray crystallography, and their structures were elucidated by spectroscopic and chemical methods.     

枸骨叶的化学成分研究

目的研究枸骨Ilex cornuta叶的化学成分。方法利用硅胶、凝胶等柱色谱和半制备高效液相色谱对枸骨叶的化学成分进行分离纯化,利用光谱数据结合理化性质鉴定其结构。结果分离得到了12个化合物,分别鉴定为(2R,3S,4S)-4-(4-hydroxy-3-methoxybenzyl)-2-(5-hydroxy-3-methoxyphenyl)-3-hydroxymethyl-tetrahydrofuran-3-ol(1)、大黄素甲醚(2)、11-酮基-α-香树脂棕榈酸酯(3)、羽扇豆醇(4)、30-醛基羽扇豆醇(5)、乌索醇(6)、3β-羟基-乌索-11-烯-13β(28)-内酯(7)、乌索酸(8)、β-谷甾醇(9)、胡萝卜苷(10)、坡模酸-28-O-β-D-葡萄糖苷(11)、长梗冬青苷(12)。结论化合物1和2为首次从冬青属中分离得到,化合物11和12为首次从该植物中分离得到。     

Microbial and chemical transformation studies of the bioactive marine sesquiterpenes (S)-(+)-curcuphenol and -curcudiol isolated from a deep reef collection of the Jamaican sponge Didiscus oxeata

Microbial and chemical transformation studies of the marine sesquiterpene phenols (S)-(+)-curcuphenol (1) and (S)-(+)-curcudiol (2), isolated from the Jamaican sponge Didiscus oxeata, were accomplished. Preparative-scale fermentation of 1 with Kluyveromyces marxianus var. lactis (ATCC 2628) has resulted in the isolation of six new metabolites: (S)-(+)-15-hydroxycurcuphenol (3), (S)-(+)-12-hydroxycurcuphenol (4), (S)-(+)-12,15-dihydroxycurcuphenol (5), (S)-(+)-15-hydroxycurcuphenol-12-al (6), (S)-(+)-12-carboxy-10,11-dihydrocurcuphenol (7), and (S)-(+)-12-hydroxy-10,11-dihydrocurcuphenol (8). Fourteen-days incubation of 1 with Aspergillus alliaceus (NRRL 315) afforded the new compounds (S)-(+)-10beta-hydroxycurcudiol (9), (S)-(+)-curcudiol-10-one (10), and (S)-(+)-4-[1-(2-hydroxy-4-methyl)phenyl)]pentanoic acid (11). Rhizopus arrhizus (ATCC 11145) and Rhodotorula glutinus (ATCC 15125) afforded (S)-curcuphenol-1alpha-D-glucopyranoside (12) and (S)-curcudiol-1alpha-D-glucopyranoside (13) when incubated for 6 and 8 days with 1 and 2, respectively. The absolute configuration of C(10) and C(11) of metabolites 7-9 was established by optical rotation computations. Reaction of 1 with NaNO(2) and HCl afforded (S)-(+)-4-nitrocurcuphenol (14) and (S)-(+)-2-nitrocurcuphenol (15) in a 2:1 ratio. Acylation of 1 and 2 with isonicotinoyl chloride afforded the expected esters (S)-(+)-curcuphenol-1-O-isonicotinate (16) and (S)-(+)-curcudiol-1-O-isonicotinate (17), respectively. Curcuphenol (1) shows potent antimicrobial activity against Candida albicans, Cryptococcus neoformans, methicillin-resistant Staphylococcus aureus, and S. aureus with MIC and MFC/MBC ranges of 7.5-25 and 12.5-50 microg/mL, respectively. Compounds 1 and 3 also display in vitro antimalarial activity against Palsmodium falciparium (D6 clone) with MIC values of 3600 and 3800 ng/mL, respectively (selectivity index >1.3). Both compounds were also active against P. falciparium (W2 clone) with MIC values of 1800 (S.I. >2.6) and 2900 (S.I. >1.6) ng/mL, respectively. Compound 14 shows anti-hepatitis B virus activity with an EC(50) of 61 microg/mL.     

Phytochemical studies on Stemona plants: isolation of stemofoline alkaloids

Six new stemofoline alkaloids, (2'R)-hydroxystemofoline (5), (3'R)-stemofolenol (6), (3'S)-stemofolenol (7), 1',2'-didehydrostemofoline-N-oxide (8), the first C(19) stemofoline alkaloid, methylstemofoline (9), and the first glycosidated Stemona alkaloid, stemofolinoside (10), and three known alkaloids, (2'S)-hydroxystemofoline (2), (11Z)-1',2'-didehydrostemofoline (3), and (11E)-1',2'-didehydrostemofoline (4), have been isolated from a root extract of an unidentified Stemona species. The structure and relative configuration of these new alkaloids have been determined by spectral data interpretation and from semisynthetic studies.     

Pittosporumxanthins, cycloaddition products of carotenoids with alpha-tocopherol from seeds of Pittosporum tobira

A series of carotenoid-alpha-tocopherol cycloaddition products, named pittosporumxanthins B1 ( 3), B2 ( 4), C1 ( 5), C2 ( 6), A3 ( 7), and A4 ( 8), were isolated from the seeds of Pittosporum tobira. The structures were determined to be cycloaddition products of 9' Z-antheraxanthin at the 11' and 12' positions with alpha-tocopherol ( 3 and 4), 9' Z-neoaxanthin with alpha-tocopherol ( 5 and 6), and 9 Z-violaxanthin with alpha-tocopherol ( 7 and 8) on the basis of a detailed analyses of MS and NMR spectroscopic data. The configurations of the carotenoid end groups in the pittosporumxanthins were determined by a modified Mosher's method. Compounds 3, 5, and 7 were assigned (11' R,12' S) and 4, 6, and 8 (11' S,12' R) absolute configurations using CD measurements.     

Synthesis and anti-HIV activity of lupane and olean-18-ene derivatives. Absolute configuration of 19,20-epoxylupanes by VCD

Lupane triterpenoids 2 and 5-12 and oleanene derivatives 13 and 14 were prepared from lupeol (1), betulin (3), and germanicol (4). They were tested for anti-HIV activity, and some structure-activity relationships were outlined. The 20-(S) absolute configuration of epoxylupenone (8) was assessed by comparison of the observed and DFT-calculated vibrational circular dichroism spectra. The CompareVOA algorithm was employed to support the C-20 configuration assignment. The 20,29 double bond in lupenone (2) and 3-epilupeol (15) was stereoselectively epoxidized to produce 20-(S)-8 and 20-(S)-16, respectively, an assignment in agreement with their X-ray diffraction structures.     

Triterpenoids from the resin of Styrax tonkinensis and their antiproliferative and differentiation effects in human leukemia HL-60 cells

Four new triterpenoids, 6beta-hydroxy-3-oxo-11alpha,12alpha-epoxyolean-28,13beta-olide (1), 3beta,6beta-dihydroxy-11alpha,12alpha-epoxyolean-28,13beta-olide (2), 3beta,6beta-dihydroxy-11-oxo-olean-12-en-28-oic acid (3), and 3beta-hydroxy-12-oxo-13Halpha-olean-28,19beta-olide (4), and five known triterpenes, 19alpha-hydroxy-3-oxo-olean-12-en-28-oic acid (5), 6beta-hydroxy-3-oxo-olean-12-en-28-oic acid (6), sumaresinolic acid (7), siaresinolic acid (8), and oleanolic acid (9), were isolated from the resin of Styrax tonkinensis. The structures of these triterpenoids were determined by physicochemical and spectroscopic methods. The configuration of compound 4 was confirmed by X-ray crystallographic analysis. All these triterpenoids inhibited HL-60 cell growth with IG(50) values ranging from 8.9 to 99.4 microM. Oleanolic acid (9) was the most effective antiproliferative agent, with an IG(50) value of 8.9 microM. While 3beta,6beta-dihydroxy-11-oxo-olean-12-en-28-oic acid (3) exhibited the least effective growth inhibition among these triterpenoids, it induced HL-60 cells to undergo differentiation as measured by an NBT reduction assay.     

Absolute configuration of verticillane diterpenoids by vibrational circular dichroism

Good agreement between theoretical and experimental vibrational circular dichroism curves of (1S,11S,12S)-(+)-verticilla-3E,7E-dien-12-ol (1) established the absolute configuration of this natural diterpene isolated from Bursera suntui. Molecular modeling of 1 was carried out using the Monte Carlo protocol followed by geometry optimization at the B3LYP 6-31G(d,p) level of theory. The 12-membered ring of 1 was found in a single preferred chair-chair-chair-chair conformation. In the six-membered ring a chair prevails over a distorted boat, and the C-OH bond rotation generates three predominant rotamers. Validation of the minimum energy conformation for 1 was achieved by comparison of theoretical and experimental infrared frequencies, vicinal 1H NMR coupling constants, and X-ray diffraction data. This study confirms that (+)-verticillol 1 isolated from Bursera species has the 1S,11S,12S absolute configuration that corresponds to the same enantiomeric series as verticillanes from Sciadopitys and Taxus, while verticillanes from Jackiella and Jungermannia have antipodal structures.     

Immunomodulatory constituents from an Ascomycete, Eupenicillium crustaceum, and revised absolute structure of macrophorin D

Fractionation guided by immunomodulatory activity of the EtOAc extract of the Ascomycete Eupenicillium crustaceum has afforded two new naturally occurring products, 4'-oxomacrophorin D (1) and 4'-oxomacrophorin A (2), as the immunosuppressive components of this fungus [1: 3-hydroxy-3-methylglutaryl (HMG) conjugate of 2]. The structures including the absolute configurations of 1 and 2 have been determined on the basis of chemical correlation of 1 with macrophorin D (3). The absolute configuration of the HMG moiety in 3 has been revised from 3R to 3S.     

瑞香狼毒细胞培养物的化学成分研究

采用常压与减压硅胶柱色谱、半制备HPLC、Sephadex LH-20等方法,从瑞香狼毒Stellera chamaejasme细胞培养物85％乙醇提取物的乙酸乙酯部分分离纯化得到了17个化合物,依据理化性质和各种波谱技术分别鉴定为:丁香脂素(1),杜仲树脂酚(2),松脂素(3),(1R,2S,5R,6S) -2-(4-hydroxyphenyl) -6-( 3-methoxy-4- hydroxyphenyl)-3,7-dioxabicyclo[3,3,0]octane(4),表松脂酚(5),caruilignan D(6),3-羰基愈创木烷-4-烯-11,12-二醇(7),落叶松脂素(8),tetrahydro-2-( 4-hydroxy-3-methoxyphenyl) -4-[ (4-hydroxyphenyl) methyl] -3-furanmethanol(9),5′-甲氧基落叶松脂醇(10),vladinol D( 11),环(L-脯氨酸-L-缬氨酸)(12),7′-羰基马台树脂醇(13),(+) -guayarol( 14),acutissimalignanB(15),异落叶松脂素(16)以及β-谷甾醇(17).其中化合物12为环二肽类化合物,7为倍半萜类化合物.除化合物7,12与17外,其余均为木脂素类化合物.17个化合物均首次从该植物组织培养物中获得.     

野菊花心血管活性部位化学成分的研究

目的:研究菊科植物野菊花心血管活性部位中的主要化学成分.方法:采用多种色谱方法进行分离纯化,通过波谱方法结合文献对照鉴定化合物结构.结果:从野菊花心血管活性部位中分离并鉴定了12个化合物,包括7个黄酮类化合物(1～7),5个苯丙素类化合物(8～12),分别鉴定为(2S)-圣草酚-7-O-β-D-吡喃葡萄糖醛酸苷(1),(2S)-圣草酚-7-O-β-D-吡喃葡萄糖苷(2),(2S)-橙皮素-7-O-β-D-吡喃葡萄糖醛酸苷(3),木犀草素-7-O-β-D-吡喃葡萄糖苷(4),木犀草素-7-O-β-D-吡喃葡萄糖醛酸苷(5),香叶木素-7-O-β-D-吡喃葡萄糖醛酸苷(6),槲皮素-7-O-β-D-呲喃葡萄糖苷(7),3,5-二咖啡酰奎宁酸甲酯(8),3,5-二咖啡酰奎宁酸(9),3,5-二顺式咖啡酰奎宁酸(10),1,5-二咖啡酰奎宁酸(11),1,3-二咖啡酰奎宁酸(12).结论:野菊花心血管活性部位中主要成分为黄酮类化合物,共5个化合物分别为2～3,7～8,10;共10个化合物分别为2～3,5～12系首次从该种植物分离得到.     

Cadinane sesquiterpenes from the brown alga Dictyopteris divaricata

Seven new cadinane sesquiterpenes, (-)-(1R,6S,7S,10R)-1-hydroxycadinan-3-en-5-one (1), (+)-(1R,5S,6R,7S, 10R)-cadinan-3-ene-1,5-diol (2), (+)-(1R,5R,6R,7S,10R)-cadinan-3-ene-1,5-diol (3), (+)-(1R,5S,6R,7S,10R)-cadinan-4(11)-ene-1,5-diol (4), (+)-(1R,5R,6R,7R,10R)-cadinan-4(11)-ene-1,5,12-triol (5), (-)-(1R,4R,5S,6R,7S, 10R)-cadinan-1,4,5-triol (6), and (-)-(1R,6R,7S,10R)-11-oxocadinan-4-en-1-ol (7), together with nine known compounds were isolated from the brown alga Dictyopteris divaricata. The structures of the new natural products, as well as their absolute configuration, were established by means of spectroscopic data including IR, HRMS, 1D and 2D NMR, single-crystal X-ray diffraction, and CD. All compounds were inactive against several human cancer cell lines including lung adenocarcinoma (A549), stomach cancer (BGC-823), breast cancer (MCF-7), hepatoma (Bel7402), and colon cancer (HCT-8) cell lines.