Inhibition of lipid peroxidation by diterpenoid fromPodocarpus nagi

A diterpenoid, totarol (1), fromPodocarpus nagi was evaluated as an antioxidant. This diterpenoid inhibited autoxidation of linoleic acid. Mitochondrial and microsomal lipid peroxidation induced by Fe(III)-ADP/NADH or Fe(III)-ADP/NADPH were also inhibited. Nagilactone E (2), a norditerpene lactone isolated from the same source, had no antioxidative activity. Furthermore, totarol protected red cells against oxidative hemolysis. This diterpene was shown to be effective in protecting biological systems against oxidative stresses.     

Biomimetic synthesis of cannabispiran

Summary Total synthesis of cannabispiran (1) was accomplished by a biomimetic-type cyclization of the bibenzyl2, using K₃Fe(CN)₆ or MoOCl₄.Acknowledgment. Supported in part by the Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi.     

Prevention of enteral radiocesium absorption by hexacyanoferrates(II) in piglets

Summary The efficacy of different hexacyanoferrates(II) in preventing the enteral absorption of¹³⁴Cs was studied in piglets. As compared to the controls, oral application of¹³⁴Cs together with KFe[Fe(CN)₆], NH₄Fe[Fe(CN)₆], or Fe₄[Fe(CN)₆]₃ resulted in a strong reduction of the¹³⁴Cs-uptake by more than 97%. The decrease in enteral absorption depends on the dose of administered hexacyanoferrate(II), whereas differences between the compounds under study were small. The biological half-life of¹³⁴Cs in non-hexacyanoferrate(II) treated piglets was 21.6±3.3 days (mean±SD).     

Zonaroic acid from the brown seaweedDictyopteris undulata (=zonarioides)

Summary A sesquiterpene-substituted 4-hydroxybenzoic acid, zonaroic acid (5), is described from the brown seaweedDictyopteris undulata (=zonarioides). The absolute stereochemistry in the zonarol (1)-chromazonarol (2) and zonaroic acid (5) series has also been defined. The occurrence of5 along with zonarol (1), the corresponding sesquiterpene-substituted hydroquinone, suggests that 4-hydroxybenzoic acid is the ring precursor as in ubiquinone biogenesis.     

Physical halflife of radiochemically pure (> 99.9999%) P59Fe and its metabolicturnover rate in man

Zusammenfassung Erstmalig wurde radiochemisch reines⁵⁹Fe (> 99,9999%) eingesetztg, um die radioaktive Halbwertzeit des⁵⁹Fe mit 44,52±0,016 (¯m _a ±SE) Tagen entsprechend einer Umwandlungskonstanten=0.015568±0.000 0056 [d^–1] zu bestimmen. Radiochemisch reines⁵⁹Fe wird im menschlichen Körper bei Männern mit einer Umsatzrate von 0,032%/Tag (=1,2 mg Fe/Tag) und bei menstruierenden Frauen mit 0,052%/Tag (=1,4 mg Fe/Tag) ausgeschieden. Diese Gesamtkörper-⁵⁹Fe-Eliminationsrate entspricht dem Eisenbedarf des Menschen.     

Research Articles¶Naturally occurring 2′-O-methylpurine nucleosides with hypotensive properties

2′-O-Methylinosine (1) has been isolated for the first time and shown to be an intrinsic hypotensive principle. Its probable in vivo precursor, 2′-O-methyladenosine (3), showed stronger and even orally potent hypotensive activity. Resistance of the methyladenosine (3) against adenosine deaminase is thought to contribute to its long-lasting activity. The effect of both nucleosides (1 and 3) was not accompanied with any significant change in heart rate, which is often observed with adenosine. Received 2 October 1997; accepted 28 October 1997     

Biotransformation of the flavonoid tiliroside to 7-methylether tiliroside: bioactivity of this metabolite and of its acetylated derivative

Incubation of kaempferol-3-O-β-D-(6"-E-p-coumaroyl)-glucopyranoside (tiliroside) (1) with Aspergillus nidulans gives the 7-methyl ether of tiliroside (2) which is a new compound. Its structure is determined by spectroscopic methods. Cytotoxic studies of 2 and of its acetylated derivative 2a were carried out in vitro against fourteen human leukemic cell lines. Results clearly show that compound 2 is ineffective against all leukemic cell lines tested. On the contrary, compound 2a exhibited cytotoxic activity against four of the cell lines (HL60, DAUDI, HUT78 and MOLT3) and additionally, a dose- and time-dependent effect on DNA synthesis. Received 18 February 1997; received after revision 8 April 1997; accepted 6 May 1997     

Creatol (5-hydroxycreatinine), a new toxin candidate in uremic patients

Summary Both 5-hydroxy-1-methylhydantoin (3) and the hitherto unrecognized 5-hydroxycreatinine (2-amino-5-hydroxy-1-methyl-imidazol-4(5H)-one or creatol) (6) can be isolated from the urine of uremic patients, in whom these compounds probably arise as oxidative metabolites of creatinine (1). The enhanced production of the well-known uremic toxin, methylguanidine (8), from creatinine (1) in such patients, almost certainly occurs via the newly recognized metabolite (6).     

On the synthesis of serine and homoserine samples asymmetrically labelled with tritium and deuterium in the hydroxymethylene group

Summary (1 R) [1-³H,²H₁] 3-Phenylpropanol, the key intermediate in the synthesis of (4 R) [4-³H,²H₁] D, L-homoserine and of the (4 S)-isomer, is obtained from (1 S) [1-²H₁] 3-phenylpropanol and (1 RS) [1-³H] ethanol upon incubation with yeast alcohol dehydrogenase and NAD⁺; under similar conditions 2-phenylethanol undergoes very small exchange with [1-²H₂] ethanol.     

Chemical defense in the three European species ofCrematogaster ants

The composition of the Dufour gland of the antC. scutellaris has been reinvestigated by gas chromatography/mass spectrometry. The major components of the gland are (2E,5E,12Z)-4-oxoheneicosa-2,5,12-trien-1-ol acetate (1a) its ¹⁴ and ¹⁶ double bond isomers (1b and1c), and the corresponding (Z,Z)-dienes5a and5b, all containing an acetylated C₂₁ chain. The previously proposed structures1d, 1e, and5c, which are based on an homologous acetylated C₂₃ chain, correspond to minor derivatives present in the gland. Traces of acetylated C₁₉ homologs, tentatively identified as1g-1i, have also been found. The Dufour gland contents of the two other EuropeanCrematogaster species have also been studied.C. auberti is very similar toC. scutellaris in producing mainly1a, 1b and1c, together with the same higher and lower homologs, but it lacks the dienic derivatives5, whereasC. sordidula contains essentially the acetylated C₁₉ compounds1g, 1h, and1i, accompanied by acetylated C₁₇ homologs.     

Observations on the toxicity and metabolic relationships of polygodial,the chemical defense of the nudibranchDendrodoris limbata

Summary Polygodial (1), the defense metabolite stored in the skin of the nudibranchDendrodoris limbata, is toxic for the mollusc itself when injected into the hepatopancreas. Biosynthetic experiments using labeled mevalonic acid were devised to investigate a possible metabolic relationship between1 and the mixture of sesquiterpenoidic esters2, stored in the hepatopancreas. The results suggest that1 and2 are biosynthesized by independent pathways.Thanks are due to G. Villani for supplyingDendrodoris limbata and to A. Trabucco for technical assistance.     

Antitumor activity of the isodon diterpenoids: Structural requirements for the activity

Summary A significant antitumor activity of oridonin (1) and lasiokaurin (2), the kaurene-type diterpenoids ofIsodon species, was shown by their i.p. injection to the test mice inoculated by Ehrlich ascites carcinoma. Enmein (8), compounds9 and3 were also active under larger dose. Subsequently, the relationship between their chemical structure and antitumor activity was investigated, and the activity of oridonin (1) and lasiokaurin (2) was rationalized in terms of their structural feature.     

Diketopiperazines containing L-proline from Streptomyces lavendulae and their stereochemistry in solution

Summary l-Valyl-l-proline (I),l-leucyl-l-proline (II),l-phenylalanyl-l-proline (III) andl-isoleucyl-l-proline (IV) anhydrides were isolated from the cultures ofStreptomyces lavendulae No. 314 and, on the basis of¹³C-NMR and CD spectra, their stereochemistry in solution is described.Acknowledgments. The authors would like to express their sincere thanks to Prof. H. Ogura, Kitasato University, for kind supply of the authenticl-valyl-l-proline anhydride and to Mr. A. Takakuwa, JASCO, for measuring the CD curves with J-40 automatic recording spectropolarimeter.     

Silymarin,an inhibitor of prostaglandin synthetase

Summary Silybin (I), silydianin (II) and silychristin (III), the main constituents of silymarin, inhibit the formation of prostaglandins in vitro. The inhibition is log-linearly dependent on the concentration of the effectors.F. Fiebrich, Thesis, University of Vienna 1977.H. Koch, Dt. ApothZtg118, 1844 (1978); reported in part at the Colloquium Pharmaceuticum in Münster, 21st November 1978.     

Further perhydroazulene diterpenes from marine organisms

Summary 3 novel diterpenes,4–6, having the perhydroazulene skeleton already found in pachydictiol A (1) and dictyol A (2) and B (3), have been isolated from both the digestive gland of Aplysia depilans and algae of the family Dictyotaceae.     

Annonacin,a novel,biologically active polyketide fromAnnona densicoma

Summary A new linear polyketide, Annonacin (I), has been isolated from active extracts of the stembark ofAnnona densicoma Mart. Annonacin (I) is highly cytotoxic and is active in an assay designed to detect antimitotic agents. The structure of (I) was determined by analysis of spectroscopic data.25 September 1986     

Guggulsterol-like steroids from the Mediterranean gorgonianLeptogorgia sarmentosa

Summary Several polyoxygenated steroids (1, 2, 3) have been isolated from the marine gorgonianLeptogorgia sarmentosa. One of these (1) is the known guggulsterol III, previously found in the pharmacologically active resin from the treeCommiphora mukul; the others,2 and3, have not been found before in nature, and are closely related to1. During the structural work apparent anomalies in the CMR-spectra of1 were observed.The authors are grateful to Prof. Sukh Dev for the PMR-spectra of guggulsterol III. Thanks are also due to Zoological Station (Naples), for the collection of the gorgonian, to Centro Metodologie Chimico-Fisiche, Università di Napoli, for recording PMR-spectra on WH-270 Superconducting Spectrometer-Bruker, to Mr C. Di Pinto for the CMR-spectra and to Mr A. Milone for the MS spectral measurements.     

Constituents of propolis

Summary The major constituents of propolis collected in Western Australia have been isolated and identified as pterostilbene (5), xanthorrhoeol (6), sakuranetin (2) and pinostrobin (1).Acknowledgments. We gratefully acknowledge Dr H. Duewell of the University of Newcastle, New South Wales, for an authentic sample of xanthorrhoeol.     

Antimutagenic unusual amino acids from plants

Summary Five unusual amino acids were identified as antimutagens against spontaneous mutation ofSalmonella typhimurium TA100: L-azetidine-2-carboxylic acid (1) from Liliaceae plants, -(methylenecyclopropyl)glycine (2) fromLitchi chinensis seeds, and 2-amino-4-methylhex-5-ynoic acid (3), hypoglycin A (4), and (2S, 4R)-2-amino-4-hydroxyhept-6-ynoic acid (5) fromEuphoria longana seeds. The absolute stereochemistry of5 was determined by its chiral synthesis from L-allylglycine, proving that5 is the C-4 epimer of the amino acid previously isolated from dried longan seeds.This work was partly supported by a Grant-in-Aid form the Ministry of Education, Science, and Culture, Japan, No. 57740283 (to HK).     

Inhibitory effect of flavonoids on DNA-dependent DNA and RNA polymerases

Summary Flavonoids, (–)-epigallocatechin (1), myricetin (2) and quercetin (3), were investigated for inhibitory effects onE. coli DNA polymerase I and T7 bacteriophage RNA polymerase. In both DNA and RNA synthesis,1 and3 inhibited enzyme reactions by non-competitive and mixed type inhibition respecitively, with regard to template DNAs. Myricetin (2) inhibited DNA and RNA polymerase reactions by mixed type and competitive type inhibition, respectively, with template DNAs. It was suggested that2 interacts with covalently closed/circular DNA.