Transformation of a monoterpene ketone, piperitenone, and related terpenoids using Mucor piriformis

Biotransformation of piperitenone (I), 5,5-dimethyl-2-(1-methylethylidene)-cyclohexanone (II), and 2-(1-ethyl-1-propylidene)-5-methylcyclohexanone (III) was studied using a versatile fungal strain, Mucor piriformis. The organism initiates transformation of these compounds by hydroxylation at the allylic positions or at the tertiary carbon. Transformation of piperitenone (I) by this strain yielded 5-hydroxypiperitenone (Ic), 7-hydroxypiperitenone (Id), 7-hydroxypulegone (Ie), 10-hydroxypiperitenone (If), and 4-hydroxypiperitenone (Ig) as metabolites. It was possible to block some of the metabolic activities of the organism through structural modification of piperitenone (I). This was evidenced by the fact that biotransformation of 5,5-dimethyl-2-(1-methylethylidene)-cyclohexanone (II) yielded 5,5-dimethyl-2-(1-hydroxy-1-methylethyl)-2-cyclohexen-1-one (IIb) and 5,5-dimethyl-3-hydroxy-2-(1-methylethylidene)-cyclohexanone (IIa), whereas 2-(1-ethyl-1-propylidene)-5-methylcyclohexanone (III) yielded 6-(1-ethyl-1-propylidene)-5-methyl-2-cyclohexen-1-one (IIIb) and 6-(1-ethyl-1-propylidene)-5-hydroxy-5-methylcyclohexanone (IIIa) as metabolites. Based on the identification of the metabolites, pathways for the biotransformation of I, II, and III have been proposed. The mode of biotransformation of these compounds by M. piriformis also compared to their modes of metabolism in the rat system.     

Secondary products in mycorrhizal roots of tobacco and tomato

Colonization of the roots of various tobacco species and cultivars (Nicotiana glauca Grah., N. longiflora Cav., N. rustica L., N. tabacum L., N. tabacum L. cv. Samsun NN, N. sanderae hort. Sander ex Wats.) as well as tomato plants (Lycopersicon esculentum L. cv. Moneymaker) by the arbuscular mycorrhizal fungus Glomus intraradices Schenck and Smith resulted in the accumulation of several glycosylated C13 cyclohexenone derivatives. Eight derivatives were isolated from the mycorrhizal roots by preparative high performance liquid chromatography (HPLC) and spectroscopically identified (MS and NMR) as mono-, di- and triglucosides of 6-(9-hydroxybutyl)-1,1,5-trimethyl-4-cyclohexen-3-one and monoglucosides of 6-(9-hydroxybutyl)-1,5-dimethyl-4-cyclohexen-3-one-1-carboxylic acid and 6-(9-hydroxybutyl)-1,1-dimethyl-4-cyclohexen-3-one-5-carboxylic acid. In contrast to the induced cyclohexenone derivatives, accumulation of the coumarins scopoletin and its glucoside (scopolin) in roots of N. glauca Grah. and N. tabacum L. cv. Samsun NN, was markedly suppressed.     

Biotransformation of alpha-isomethylionone to 1-(2,6,6-trimethyl-2-cyclohexen-1-yl)propan-2-one

The main biodegradation product of (+/-)-alpha-isomethylionone (2) with standard activated sludge was characterized as (+/-)-1-(2,6,6-trimethyl-2-cyclohexen-1-yl)propan-2-one (1) by its analysis and synthesis. Both enantiomers (1a and 1b) of 1 were synthesized by starting from (R)- and (S)-2,4,4-trimethyl-2-cyclohexen-1-ol (3a and 3b), respectively.     

Synthesis and antinematodal activity of 3-n-alkylphenols

Several 3-alkylphenols including 3-undecylphenol, which was isolated from a Sumatran rainforest plant, were synthesized to investigate their antinematodal activity against the phytopathogenic nematodes, Bursapherencus xylophilus. A three-step synthesis involving the treatment of 2-cyclohexen-1-one with the Grignard reagent, oxidation of the resulting 1-alkyl-2-cyclohexen-1-ol and subsequent aromatization of 3-alkyl-2-cyclohexen-1-one successfully afforded such phenols. Among the 3-alkylphenols, 3-nonylphenol showed the highest activity, while 3-decylphenol and 3-undecylphenol also showed high activity.     

Synthesis and Antinematodal Activity of 3-n-Alkylphenols

Several 3-alkylphenols including 3-undecylphenol, which was isolated from a Sumatran rainforest plant, were synthesized to investigate their antinematodal activity against the phytopathogenic nematodes, Bursapherencus xylophilus. A three-step synthesis involving the treatment of 2-cyclohexen-1-one with the Grignard reagent, oxidation of the resulting 1-alkyl-2-cyclohexen-1-ol and subsequent aromatization of 3-alkyl-2-cyclohexen-1-one successfully afforded such phenols. Among the 3-alkylphenols, 3-nonylphenol showed the highest activity, while 3-decylphenol and 3-undecylphenol also showed high activity.     

Chemical constituents from the fresh flower buds of Musa nana and their chemotaxonomic significance

Phytochemical study on the fresh flower of Musa nana Lour. provided seventeen known compounds including two alkaloids, 3-(hydroxyacetyl)-indole (1), bi-indol-3-yl (2), two terpenoids, 5-[(1R)-1-hydroxy-2,6,6-trimethyl-4-oxo-2-cyclohexen-1-yl]-3-methyl-, (2Z, 4E) −2, 4-pentadienoic acid (Valdes), 5, 6(S), 7, 7a(R)-tetrahydro-6-hydroxy-4,4-dimethyl-2(4H)-benzofuranone (4), seven phenols (5–11), three phenylphenalenones, 2-hydroxy-4-(4-methoxyphenyl)-1H-phenalen-1-one (12), 2-methoxy-9-phenyl-1H-phenalen-1-one (13), 2-methoxy-9-(4-methoxyphenyl)-1H-phenalen-1-one (14), and three lipids (15–17). In the present study, all the compounds were isolated for the first time from the species M. nana. Ten compounds including 1-8 and 15-16 have never been previously encountered in the Musaceae family. Furthermore, the chemotaxonomic significance of these isolates was also discussed.     

Stereostructure of curlone,a sesquiterpenoid of Curcuma longa rhizomes

From the crude drug ‘ukon’ (turmeric) (obtained from the rhizomes of Curcuma longa) a new sesquiterpenoid, curlone, has been isolated and shown as (6S)-2-methyl-6-[(1S)-4-methylene-2-cyclohexen-1-yl]-2-hepten-4-one on the basis of its spectral properties and its chemical conversion to the known (+)-ar-turmerone.     

Accumulation of cyclohexenone derivatives in barley, wheat and maize roots in response to inoculation with different arbuscular mycorrhizal fungi

Glomus intraradices , Glomus mosseae, and Gigaspora rosea leads to the accumulation of cyclohexenone derivatives. Mycorrhizal roots of all plants accumulate in response to all three fungi blumenin [9-O-(2′-O-glucuronosyl)-β-glucopyranoside of 6-(3-hydroxybutyl)-1,1,5-trimethyl-4-cyclohexen-3-one], 13-carboxyblumenol C 9-O-gentiobioside, nicoblumin [9-O-(6′-O-β-glucopyranosyl)-β-glucopyranoside of 13-hydroxy-6-(3-hydroxybutyl)-1,1,5-trimethyl-4-cyclohexen-3-one] and another, as yet unidentified, cyclohexenone derivative. The accumulation of all four compounds in three tested mycorrhizal plants colonized by the three arbuscular mycorrhizal fungi indicates no fungus-specific induction of these compounds. Accepted: 6 October 1999     

First synthesis of (+/-)-robinlin

The first synthesis of (+/-)-robinlin (1), a novel homo-monoterpene with strong bioactivity in the brine shrimp lethality test, was achieved by starting from 3-isobutyloxy-2,6,6-trimethyl-2-cyclohexen-1-one (2).     

Synthesis and evaluation of antifungal properties of a series of the novel 2-amino-5-oxo-4-phenyl-5,6,7,8-tetrahydroquinoline-3-carbonitrile and its analogues

A series of 2-amino-5-oxo-4-phenyl-5,6,7,8-tetrahydroquinoline-3-carbonitrile and various analogues have been synthesized in excellent isolated yields starting from various arylidenemalononitrile and 3-amino-2-cyclohexen-1-one in 1-propanol as solvent at reflux temperature in the absence of any added catalyst. All the synthesized compounds were evaluated for their antifungal activity. The relationship between functional group variation and biological activity of the evaluated compounds is discussed in the article.     

Alpha-pyrones and a 2(5H)-furanone from Hyptis pectinata

Three pyrones and a 2(5H)-furanone, designated pectinolides D-G, have been isolated from the dichloromethane extract of Hyptis pectinata. The metabolites were characterized on the basis of 1D and 2D NMR spectroscopic techniques. The pyrones were identified as 6S-[3S,6S-(diacetoxy)-5R-hydroxy-1Z-heptenyl]-5S-hydroxy-5,6-dihydro-2H-pyran-2-one (1)- pectinolide D, 6S-[3S,5R,6S-(triacetoxy)-1Z-heptenyl]-5S-acetoxy-5,6-dihydro-2H-pyran-2-one (2)- pectinolide E and 6S-[3S,5R,6S-(triacetoxy)-1Z-heptenyl]-5S-acetoxy-4R-methoxy-3,4,5,6-tetrahydro-4H pyran-2-one (3)- pectinolide F. The furanone was identified as [2'Z,5(1')Z] 5-(4'S,6'R,7'S-triacetoxy-2-octenylidene)-2(5H)-furanone (4)-pectinolide G.     

Urease inhibitory activity of simple alpha,beta-unsaturated ketones

A variety of alpha,beta-unsaturated ketones were evaluated for their effect on the jack bean urease. Of 35 compounds tested, 2-cyclohepten-1-one (1), 2-cyclohexen-1-one (2), 2-cyclopenten-1-one (3), and 5,6-dihydro-2H-pyran-2-one (4) showed potent inhibitory activities against the enzyme. The most potent compound (1) (IC50=0.16 mM) showed similar inhibitory potency to hydroxyurea (IC50=0.095 mM). The inhibitory effects of 1, 2, 3, and 4 were significantly reduced by 2-mercaptoethanol or dithiothreitol. These data suggest that alpha,beta-unsaturated ketones inhibited the urease activity, possibly by a Michael-like addition of a protein SH group to the double bond of the alpha,beta-unsaturated carbonyl group.     

Reduction screening with endophytic fungi: Synthesis of homochiral secondary alcohols

Twelve strains of endophytic fungi, isolated from various plants (i.e. Eugenia hallii, Schinus molle, Crataegus monogyna, Juniperus communis and Sambucus nigra) sampled in Amazonian forest and in Italy, were screened for their reduction activity with a cocktail of ketones 1–4. The four most active strains [i.e. Phomopsis (FE86 and FE290), Pestalotia and Epicoccum] were chosen for the reduction of 5-hexen-2-one 1, acetophenone 2, cis-bicyclo[3.2.0]hept-2-en-6-one 3, 2-methylcyclohexanone 4, 6-methyl-5-hepten-2-one 5, 2-furyl methyl ketone 6, 1-indanone 7, and 2,4,4-trimethyl-2-cyclohexen-1-one 8 and in all cases the S-alcohols were obtained with variable yields and enantiomeric excesses depending on the strains.     

Synthesis of 5-hydroxy-2-(beta-D-ribofuranosyl)pyran-4-one from a pyranulose glycoside.

The synthesis of 5-hydroxy-2-(beta-D-ribofuranosyl)pyran-4-one (9) is described. Treatment of pyranulose glycoside with bromine in carbon tetrachloride afforded brompyranulose glycoside in 90% yield. The reaction of (6S)- and (6R)-4-bromo-6-hydroxy-6-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-6H- pyran-3-one (2) in acidic media was examined with the following results: the reaction of 2 with trifluoroacetic acid (TFA) in dioxane afforded a mixture of 5-hydroxy-2-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)pyran-4-one (3) and its furan derivative 5-hydroxy-2-{5-(benzoyloxy)methyl]furan-2-yl}pyran-4-one (4), but the use of hydrochloric acid formed the bromofurfural, 3-bromo-5-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-2-furancarboxyal dehyde only. Acetylation of a mixture (3 and 4) with acetic anhydride facilitated product separation to give the corresponding acetates 5-acetoxy-2-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)pyran-4-one (5) and 5-acetoxy-2-{5-[(benzoyloxy)methyl]furan-2-yl}pyran-4-one (6). Treatment of 5 with hydrazine afforded 3-hydroxymethyl-6-(beta-D-ribofuranosyl)-1H-pyridazin-4-one in 43% yield. Debenzoylation of 5 with aq ammonia gave 9 in 50% yield.     

Enantioselective conjugate addition of diethylzinc to cyclic enones catalyzed by copper complexes of methylene-bridged P-chirogenic diphosphines

The copper-catalyzed enantioselective conjugate addition of diethylzinc to 2-cyclohexen-1-one was investigated using (R,R)-bis-(t-butylmethylphosphino)methane (1c) as a chiral ligand. The reaction was carried out at 0 degrees C in THF-toluene as the solvent system and in the presence of 1.2 mol% of CuOTf afforded (S)-3-ethylcyclohexan-1-one with 85% ee.     

A New Keto-alcohol, (−)-Mintlactone, (+)-isoMintlactone and Minor Components in Peppermint Oil

Eighty-one constituents were newly identified from the oil of Mentha piperita L., including a new keto-alcohol, (?)-mintlactone and (+)-isomintlactone. They were determined by spectral data and syntheses to be 4-hydroxy-4-methyl-2-cyclohexen-1-one (8), (6R, 7aR) (10) and (6R, 7aS)-3,6-dimethyl-5,6,7,7a-tetrahydro-2(4H)-benzofuranone (11), respectively.     

2''-Deoxy-3,7-dideazaguanosine and related compounds. Synthesis of 6-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl) and 1-beta-D-arabinofuranosyl-1H-pyrrolo[3,2-c]pyridin-4(5H)-one via direct glycosylation of a pyrrole precursor.

The synthesis of two new analogs of 2'-deoxyguanosine, 6-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-1H-pyrrolo[3,2-c] pyridin-4(5H)-one (8) and 6-amino-1-beta-D-arabinofuranosyl-1H-pyrrolo[3,2-c]-pyridin-4(5H)-one (13) has been accomplished by glycosylation of the sodium salt of ethyl 2-cyanomethyl-1H-pyrrole-3-carboxylate (4c) using 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-alpha-D-erythro-pentofuranose( 5) and 1-chloro-2,3,5-tri-O-benzyl-alpha-D-arabinofuranose (9), respectively. The resulting blocked nucleosides, ethyl 2-cyanomethyl-1-(2-deoxy-3,5-di-O-p-toluoyl-beta-D-erythro- pentofuranosyl)-1H-pyrrole-3-carboxylate (6) and ethyl 2-cyanomethyl-1-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)- 1H-pyrrole-3-carboxylate, were ring closed with hydrazine to form 5-amino-6-hydrazino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-1H- pyrrolo[3,2-c]-pyridin-4(5H)-one (7) and 5,6-diamino-1-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)-1H- pyrrolo[3,2-c]pyridin-4(5H)-one (11), respectively. Treatment of 7 with Raney nickel provided the 2'-deoxyguanosine analog 8 while reaction of 11 with Raney nickel followed by palladium hydroxide/cyclohexene treatment gave the 2'-deoxyguanosine analog 13. The anomeric configuration of 8 was assigned as beta by proton NMR, while that of 13 was confirmed as beta by single-crystal X-ray analysis of the deblocked precursor ethyl 2-cyanomethyl-1-beta-D-arabinofuranosyl-1H-pyrrole-3-carboxylate (10a).     

Effect of JH III and substituted oxime ethers on the in vitro protein and RNA synthesis in male accessory reproductive gland (MARG) of Spodoptera litura (F.)

The physiological action of two substituted oxime ethers namely: 4'-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3'-buten-2'(E)-ketoxime-N-O-propylether (compound No. 3) and 4'-(2,6,6-trimethyl-1-cyclohexen-1-yl)-3'-buten-2'(E)-ketoxime-N-O-pentylether (compound No. 34,) were compared with that of JH III in an in vitro assay to monitor the synthesis of RNA and protein in male accessory reproductive gland (MARG) of Spodoptera litura by using 3H-leucine and 3H-uridine, respectively. Both the compounds have stimulated protein synthesis compare to control. Compound No 34 is slightly more effective than JH III in increasing the protein synthesis at physiological concentration of 10(-6) and 10(-5) M. Compound No 3 and JH III have doubled the RNA synthesis and increased the protein synthesis by 1.5 times over the control at 10(-4) to 10(-6) M concentrations. While JH III at 10(-5) M significantly enhanced RNA synthesis, similar effect is produced only at 10(-3) M by compound No 3 and 34.     

Synthesis and inhibitory activity of new benzimidazole derivatives against Burkitt's lymphoma promotion

As a continuation to our previous work concerning antitumor benzimidazoles, we have synthesized series of new derivatives of 2-(1-benzyl-2-methyl-1H-benzimidazol-5-ylimino)-3-(substituted)-thiazolidin-4-one (6a-e), 3-(2-methyl-1H-benzimidazol-5-yl)-2-substituted-thiazolidin-4-one (9a-f) and we have studied their inhibitory activity against the Epstein-Barr virus-early antigen (EBV-EA) activation introduced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Compound 6d was found to be significantly active and compounds 5a and 6e were also active.     

Cell-Bound Serine Proteinase of Sporulating Cells of Bacillus subtilis

2-Deuterio-2-cyclohexen-l-one, 3-deuterio-2-cyclohexen-l-one and 2-methyl-2-cyclohexen-1-one were reduced by Clostridium La 1 giving a single bioconversion product resulting from reduction of the carbon-carbon double bond. Stereochemistry of the reaction was studied.