Caldensinic acid,a prenylated benzoic acid from Piper caldense

The CH₂Cl₂ and MeOH extracts from leaves of Piper caldense were subjected to chromatographic separation procedures to afford the new prenylated benzoic acid, caldensinic acid (3-[(2′E,6′E,10′E)-11′-carboxy-3′,7′,15′-trimethylhexadeca-2′,6′,10′,14′-tetraenyl]-4,5-dihydroxybenzoic acid) whose structure was determined by spectral analysis, mainly NMR (¹H, ¹³C, HSQC, HMBC) and ESI-MS. The natural compound and derivatives displayed antifungal activity against the phytopathogenic fungi Cladosporium cladosporioides and C. sphaerospermum by direct bioautography.     

A quinone-hydroquinone couple from the Brown alga Cystoseira stricta

2′E,6′E)-2-(10′,11′-Dihydroxygeranylgeranyl)-6-methylquinol and 2′E,6′E)-2(10′,11′-dihydroxyeranylgeranyl)-6-methyl-1,4-benzoquinone have been isolated from the brown alga Cystoseira stricta. The structures of the new algal metabolites have been elucidated by spectral analysis and chemical degradation.     

Conversion of (2Z,4E)-5-(1′,2′-epoxy-2′,6′,6′-trimethylcyclohexyl)-3-methyl-2,4-pentadienoic acid to xanthoxin acid by Cercospora cruenta, a fungus producing (+)-abscisic acid

(±)-(2Z,4E)-5-(1′,2′-epoxy-2′,6′,6′-trimethylcyclohexyl)-3-methyl-2,4-pentadienoic acid was metabolized by Cercospora cruenta, which has the ability to produce (+)-abscisic acid (ABA), to give (±)-(2Z,4E)-xanthoxin acid, (±)-(2Z,4E)-5′-hydroxy-1′,2′-epoxy-1′,2′-dihydro-β-ionylideneacetic acid, (±)-1′,2′-epoxy-1′,2′-dihydro-β-ionone and trace amounts of ABA.     

Synthesis and plant growth inhibitory activities of (+)- and (−)-(2Z,4E)-5-(1′,2′-epoxy-2′,6′,6′-trimethylcyclohexyl)-3-methyl-2,4-pentadienoic acid

Chiral (+)- and (?)-enantiomers of (2Z,4E)-5-(1′,2′-epoxy-2′,6′,6′-trimethylcyclohexyl)-3-methyl-2,4-pentadienoic acid have been synthesized from the chiral epoxy alcohols (+)- and (?)-1′,2′-dihydro-1′,2′-epoxy-β-ionone, which were prepared by Katsuki-Sharpless' asymmetric epoxidation of β-cyclogeraniol. The (+)-enantiomer showed strong inhibitory activity in a rice seedling and lettuce germination assay, whereas the (?)-enantiomer was 10³-times less active.     

Three new neolignan glucosides from the stems of Dendrobium aurantiacum var. denneanum

Three new neolignan glucosides (1–3), together with four known analogs (4–7), have been isolated from the stems of Dendrobium aurantiacum var. denneanum. Structures of the new compounds including the absolute configurations were determined by spectroscopic and chemical methods as (−)-(8R,7′E)-4-hydroxy-3,3′,5,5′-tetramethoxy-8,4′-oxyneolign-7′-ene-9,9′-diol 4,9-bis-O-β-d-glucopyranoside (1), (−)-(8S,7′E)-4-hydroxy-3,3′,5,5′-tetramethoxy-8,4′-oxyneolign-7′-ene-9,9′-diol 4,9-bis-O-β-d-glucopyranoside (2), and (−)-(8R,7′E)-4-hydroxy-3,3′,5,5′,9′-pentamethoxy-8,4′-oxyneolign-7′-ene-9-ol 4,9-bis-O-β-d-glucopyranoside (3), respectively.     

Neolignans from Nectandra miranda

Seven neolignans, isolated from a C₆H₆ extract of Nectandra miranda (Lauraceae) trunk wood, included the hitherto undescribed (2S, 3S, 3aS)- and (2S, 3S, 3aR)-5-allyl-3a-methoxy-2-(3′, 4′, 5′-trimethoxyphenyl)-3-methyl-2, 3, 3a, 6-tetrahydro-6-oxobenzofurans (respectively mirandin-A and mirandin -B), 7-allyl-6-hydroxy-5-methoxy-2-(3′, 4′, 5′-trimethoxyphenyl)-3-methylbenzofuran and (2R, 3R)-7-methoxy-2-(3′, 4′, 5′-trimethoxyphenyl)-3-methyl-5 -(E)-propenyl-2, 3-dihydrobenzofuran (licarin C).     

Dimeric hydroanthracenes from the unripe seeds of Cassia torosa

From the unripe seeds of Cassia torosa three new dimeric hydroanthracene derivatives were isolated along with stigmasterol, sitosterol, campesterol, physcion-9-anthrone, torosachyrsone and the phlegmacins A₂ and B₂. The structures of the new derivatives were established as physcion-10, 10′-bianthrone, anhydrophlegmacin B₂ [2-(6′-methoxy-3′-methyl-3′, 8′, 9′-trihydroxy-1′-oxo-1′, 2′, 3′, 4′-tetrahydroanthracene-10′-yl)-1, 8-dihydroxy-3-methoxy-6-methyl-9-oxo-9, 10-dihydroanthracene] and torosanin [2-(6′-methoxy-3′-methyl-3′, 8′,9′-trihydroxy-1′-oxo-1′, 2′, 3′,4′-tetrahydroanthracene-5′-yl)-1, 8-dihydroxy-3-methoxy-6-methyl-9-oxo-9, 10-dihydroanthracene], respectively.     

Proton magnetic resonance studies of 9-(β-d-xylofuranosyl)adenine 3′,5′-cyclic monophosphate and 9-(β-d-arabinofuranosyl)adenine 2′,5′-cyclic monophosphate

A detailed ¹H 220-MHz n.m.r. study of 9-(β-d-xylofuranosyl)adenine 3′,5′-cyclic monophosphate (3′,5′-xylo-cAMP, 1) and 9-(?-d-arabinofuranosyl)adenine 2′,5′-cyclic monophosphate (2′,5′-ara-cAMP, 2) in D₂O solution is described. The sugar-ring conformations in 1 and 2 are shown to be ³E and ²E, respectively, and the phosphate rings are in a chair form. An unusual ⁴J_P,H coupling of 2.4 Hz is observed between H-4′ and phosphorus in 1 and a vicinal J_P,H of 30.8 Hz between H-5′ and phosphorus in 2. This latter coupling verifies a similar value found previously in the ara-cytidine analog of 2. A comparison of the conformational properties of cyclic nucleotides having fused phosphate and sugar rings has been made, together with an assessment of the use of the Karplus constants in such ring-systems.     

Antiproliferative constituents from Aphananthe aspera leaves

Extensive screening for the antiproliferative activity of different compounds found in trees was performed by extracting the leaves of Aphananthe aspera (Thunb.) Planch and then using chromatographic separation to afford 2 new compounds, (2S,4R)-2-carboxy-4-(E)-p-caffeoyl-1-methyl-hydroxyproline (1) and 5-O-caffeoyl quinic acid-(7′R,8′S,7′′E)-3′,4′,3′′-dihydroxy-4′′,7′-epoxy-8′,5′′-neolign-7′-ene-9- carboxyl (2). In addition, 6 known compounds were discovered from the leaves of this plant. The structural determination of all compounds, including their absolute configurations, was established by UV, IR, HRESIMS, 1D and 2D NMR, and CD spectroscopy. The novel compound 1 showed strong antiproliferative activity against human breast adenocarcinoma cells MCF-7 and MDA-MB-231.     

Neolignans from stem bark of ocotea veraguensis

The stem bark of Ocotea veraguensis has yielded nine neolignans of which five appear to be novel. The new neolignans, which were identified on the basis of spectral characteristics, are^* (7S,8R,1′S,2′S,3′R,4′S)-Δ^8′-2′,4′-dihydroxy-3,3′5′-trimethoxy-4,5-methylenedioxy-1′,2′,3′,4′-tetrahydro-7.3′,8.1′-neolignan, (7S,8R,1′S,3′S,4′S)-Δ^8′-4,4'-dihydroxy-3,3′,5′-trimethoxy-1′,2′,3′,4′-tetrahydro-2′-oxo-7.3′,8.1′-neolignan, (7S,8S,1′R)-Δ^8′-3′,5′-dimethoxy-3,4-methylenedioxy-1′,4′-dihydro-4′-oxo-7.0.2′,8.1′-neolignan, (7S,8S,1′R )-Δ^8′-1′-methoxy-3,4-methylenedioxy-1′,6′-dihydro-6′-oxo-7.0.4′,8.3′-neolignan and (7S,8S)-Δ^8′-2′,6′-dimethoxy-3,4-methylenedioxy-7.0.3′,8.4′,1′.0.7′-neolignan.     

New coumarins from Coleonema album

Six coumarins have been isolated from the aerial parts of Coleonema album and identified as ulopterol, 7-(3′, 3′-dimethylallyloxy)-coumarin, (R)-(+)-2′,3′-epoxy-suberosin, and the novel coumarins (R)-(+)-7-(2′, 3′-epoxy-3′-methylbutoxy)-coumarin, (R)-(+)-7-(2′,3′-dihydroxy-3′-dihydroxy-3′-methylbutoxy)-coumarin and (R)-(+)-7-methoxy-8-(2′,3′-epoxy-3′-methylbutoxy)-coumarin.     

Synthesis of 6-substituted uridines. synthesis of (R or S)-6-(3-amino-2-carboxypropyl)uridine

Addition of 5-bromo-2′,3′-O-isopropylidene-5′-O-trityluridine (2) in pyridine to an excess of 2-lithio-1,3-dithiane (3) in oxolane at 78° gave (6R)-5,6-dihydro-(1,3-dithian-2-yl)-2′,3′-O-isopropylidene -5′-O-trityluridine (4), (5S,6S)-5-bromo-5,6-dihydro-(1,3-dithian-2-yl)-2′,3′-O-isopropylidene-5′-O-trityluridine (5), and its (5R) isomer 6 in yields of 37, 35, and 10%, respectively. The structure of 4 was proved by Raney nickel desulphurization to (6S)-5,6-dihydro-2′,3′-O-isopropylidene-6-methyl-5′-O-trityluridine (7) and by acid hydrolysis to give D-ribose and (6R)-5,6-dihydro-6-(1,3-dithian-2-yl)uracil (9). Treatment of 4 with methyl iodide in aqueous acetone gave a 30&%; yield of (R,S)-5,6-dihydro-6-formyl-2′,3′-O-isopropylidene-5′-O-trityl-uridine (10), characterized as its semicarbazone 11. Both 5 and 6 gave 4 upon brief treatment with Raney nickel. Both 5 and 6 also gave 6-formyl-2′,3′-O-isopropylidene-5′- O-trityluridine (12) in ～41%; yield when treated with methyl iodide in aqueous acetone containin- 10%; dimethyl sulfoxide. A by-product, identified as the N-methyl derivative (13) of 12 was also formed in yields which varied with the amount of dimethyl sulfoxide used. Reduction of 12 with sodium borohydride, followed by deprotection, afforded 6-(hydroxymethyl)uridine (17), characterized by hydrolysis to the known 6-(hydroxymethyl)uracil (18). Knoevenagel condensation of a mixture of the aldehydes 12 and 13 with ethyl cyanoacetate yielded 38%; of E- (or Z-)6-[(2-cyano-2-ethoxycarbonyl)ethylidene]-2′,3′-O-isopropylidene-5′-O-trityluridine (19) and 10%; of its N-methyl derivative 20. Hydrogenation of 19 over platinum oxide in acetic anhydride followed by deprotection gave R (or S)-6-(3-amino-2-carboxypropyl)uridine (23).     

Eusiderins and other neolignans from an Aniba species

A previous report disclosed the presence of benzodioxan and bicyclo[3.2.1]octanoid neolignans in the benzene extract of the trunk wood of an Amazonian Aniba (Lauraceae) species. The chloroform extract of the same material contains additionally two new benzodioxan neolignans [rel-(7S,8R)-Δ^8′-7-hydroxy-3,4,5,5′-tetramethoxy-7.0.3′,8.0.4′-neolignan; rel-(7R,8R)-Δ^7′-3,4,5,5′-tetramethoxy-9′-oxo-7.0.3′,8.0.4′-neolignan], two new bicyclo[3.2.1]-octanoid neolignans [(7R,8S,1′S,2′S,3′S,4′R)-Δ^8′-2′,4′-dihydroxy-3,3′-dimethoxy-4,5-methylenedioxy-1′,2′,3′,4′,5′,6′-hexahydro-5′-oxo-7.3′,8.1′-neolignan; (7R,8S,1′R,2′S,3′S)-Δ^8′-2′-hydroxy-3,3′,5′-trimethoxy-4,5-methylenedioxy-1′,2′,3′,4′-tetrahydro-4′-oxo-7.3′,8.1′-neolignan] and a hydrobenzofuranoid neolignan [(7S,8R,1′S,5′S)-Δ^8′-3,3′,5′-tri-methoxy-4,5-methylenedioxy-1′,4′,5′,6′-tetrahydro-4′-oxo-7.0.2′,8.1-neolignan].     

Chemical constituents of Trilepisium madagascariense (Moraceae) and their antimicrobial activity

The chemical study of Trilepisium madagascariense has led to the isolation of two previously undescribed compounds, (+)-(2S)-7-hydroxy-3′,4′-dimethoxyflavan (trilepisflavan) and (E)-4-[3-(3,4-dihydroxyphenyl)prop-2-enoyloxy]-3-hydroxybenzoic acid (trilepisuimic acid), together with ten known compounds caffeic acid, catechin, erythrodiol-3-O-palmitate, 8-C-glucopyranosylapigenin, dihydrokaempferol, protocatechuic acid, 3′,7-dihydroxy-4′-methoxyflavan, isoliquiritigenin, luteolin and 1,3-dimethoxybenzene. Their structures were elucidated on the basis of spectroscopic evidence. Crude extracts, trilepisflavan, dihydrokaempferol and 8-C-glucopyranosylapigenin showed significant antimicrobial activity.     

Neolignans from mezilaurus itauba

The wood bark of Mezilaurus itauba afforded in addition to seven known neolignans, three new compounds rel-(7R,8R,1′S,3′S)-Δ^5′,8′-5′-methoxy-3,4-methylenedioxy-1′,2′,3′,4′-tetrahydro-2′,4′-dioxo-7.3′,8.1′-neolignan, rel-(7S,8S,1′S, 2′S, 3′R, 4′S)-Δ^8′-2′,4′-dihydroxy-3,4-methylenedioxy-1′,2′,3′,4′,5′,6′-hexahydro-5′-oxo-7.3′,8.1′-neolignan and rel-(7S,8S)-Δ^8′-6′-hydroxy 5′-methoxy-3,4-methylenedioxy-7·O·2′,8.3′-neolignan. The latter compound has been detected previously in Aniba terminalis. The structures were elucidated by spectroscopic methods and comparison with related compounds.     

Biosynthesis of the isoflavan isomucronulatol: Origin of the 2′,3′,4′-oxygenation pattern

Feeding experiments with ¹⁴C-labelled isoflavones in seedlings and pods of bladder senna (Colutea arborescens) have demonstrated that 7-hydroxy-4′-methoxyisoflavone (formononetin), 7,3′-dihydroxy-4′-methoxyisoflavone (calycosin), 7,2′,3′-trihydroxy-4′-methoxyisoflavone (koparin) and 7,2′-dihydroxy-3′,4′-dimethoxyisoflavone are excellent precursors of (3R)-isomucronulatol (7,2′-dihydroxy-3′,4′-dimethoxyisoflavan). 7,2′-Dihydroxy- 4′-methoxyisoflavone (2′-hydroxyformononetin) and 7-hydroxy-3′,4′-dimethoxyisoflavone (cladrin) were, however, poor substrates. Thus, the biosynthetic sequence to isomucronulatol from formononetin involves 3′-hydroxylation, 2′-hydroxylation and then 3′-O-methylation, followed presumably by stereospecific reduction of 7,2′-dihydroxy-3′,4′-dimethoxyisoflavone. Treatment of 2′,3′,4′-trimethoxyisoflavones with aluminium chloride in acetonitrile gives modest yields of 2′,3′-dihydroxy derivatives rather than 2′-monohydroxyisoflavones, and thus provides a convenient access to 2′,3′-dihydroxyisoflavones and related pterocarpans.     

The structure of isostrychnopentamine,a bisindole monoterpene alkaloid from Strychnos usambarensis

The alkaloid isostrychnopentamine has been shown to be epimeric with strychnopentamine at the asymmetric carbon atom of the N-methylpyrrolidin-2-yl group. Its lUPAC name is 2-[(1′,2′,3′,4′-tetrahydro-2′-methyl-β-carbolin-1′-yl)methyl]-11-(1″-methyl-pyrrolidin-2″-yl)-3-vinyl-1,2,3,4,6,7,12,12b-octahydro-indolo[2,3-a]quinolizin-10-oL [2(S),3(R),12b(S),1′(S),2″(S)].     

NMR study of dideoxynucleotides with anti-human immunodeficiency virus (HIV) activity

The molecular structures of 3′-azido-2′,3′-dideoxyribosylthymine 5′-triphosphate (AZTTP), 2′,3′-dideoxyribosylinosine 5′-triphosphate (ddITP), 3′-azido-2′,3′-dideoxyribosylthymine 5′-monophosphate (AZTMP) and 2′,3′-dideoxyribosyladenine 5′-monophosphate (ddAMP) have been studied by NMR to understand their anti-HIV activity. For ddAMP and ddITP, conformations are almost identical with their nucleoside analogues with sugar ring pucker equilibriating between C3′-endo (∼75%) and C2′-endo (∼25%). AZTMP and AZTTP on the other hand show significant variations in the conformational behaviour compared with 3′-azido-2′,3′-dideoxyribo-sylthymine (AZT). The sugar rings for these nucleotides have a much larger population of C2′-endo (∼75%) conformers, like those observed for natural 2′-deoxynucleosides and nucleotides. The major conformers around C5′-O5′, C4′-C5′ and the glycosidic bonds are the β^t, γ⁺ and anti, respectively.     

Inhibition of the β-carbonic anhydrases from Mycobacterium tuberculosis with C-cinnamoyl glycosides: Identification of the first inhibitor with anti-mycobacterial activity

A small series of C-cinnamoyl glycoside containing the phenol moiety was tested for the inhibition of the three Mycobacterium tuberculosis β-carbonic anhydrases (CAs, EC 4.2.1.1) with activities in the low micromolar range detected. The compounds were also tested for the inhibition of growth of M. tuberculosis H₃₇Rv strain, leading to the identification of (E)-1-(2′,3′,4′,6′-tetra-O-acetyl-β-d-glucopyranosyl)-4-(3-hydroxyphenyl)but-3-en-2-one (1) as the first carbonic anhydrase inhibitor with anti-tubercular activity.     

Phenolic lipids from related marine algae of the order dictyotales

2-(1′-Oxo-dodeca-5′, 8′, 11′, 14′, 17′(all Z)-pentaenyl)-5-methoxy-1, 3-dihydroxybenzene, 2- (1′-oxo-dodeca-5′, 8′, 11′, 14′, 17′(all Z)-pentaenyl)-1, 3, 5-trihydroxybenzene, 2-(17′-hydroxy-1′-oxo-dodeca-5′, 8′, 11′, 14′(all Z)-tetraenyl)-1, 3, 5-trihydroxybenzene and 2-(1′oxo-hexadecyl)-1, 3, 5-trihydroxybenzene have been isolated from the related brown algae Zonaria farlowii, Z diesingiana and Lobophora papenfussii. The structures of these new metabolites are based on extensive spectral analyses and comparisons with model compounds. The isolation of (+)-7, 8-dimethyltocol, from L. papenfussii, is also reported.