A pterocarpan and two isoflavans from alfalfa

(−)6aR,11aR-Dihydro-3-hydroxy-9,10-dimethoxy-6H-benzofuro[3,2c] [1]-benzopyran (10-methoxymedicarpin), (+)-(2,3,4,-trimethoxyphenyl)-2,3-dihydro-7-hydroxy-4H-1-benzopyran (7-hydroxy-2′,3′,4′-trimethoxyisoflavan) and (+)-(2,3,4-trimethoxy-5-hydroxyphenyl)-2,3-dihydro-7-hydroxy-4H-1-benzopyran (7,5′-dihydroxy-2′,3′,4′-trimethoxyisoflavan) were isolated for the first time from dried Medicago sativa hay. Structural assignments were based on ¹H NMR and mass spectra, X-ray crystallography, and optical rotations.     

A new synthesis of the benzofuran adenosine antagonist XH-14

5-(3-Hydroxypropyl)-7-methoxy-2-(3′-methoxy-4′-hydroxyphenyl)benzo[b]furan-3-carbaldehyde (XH-14, 1) has been reported to be a potent A₁ adenosine antagonist. We have developed an efficient synthesis of this compound that should prove valuable for further structure-activity studies. The synthesis incorporates optimised methodology for the selective protection of a hydroxyl group and the ortho-bromination of a phenol.     

Further farnesyl-homogentisic acid derivatives from Otoba parvifolia

The seeds of Otoba parvifolia contain three novel compounds apparently derived from homogentisic acid, rel-(1′R,5′R)-2-(1′-farnesyl-5′-hydroxy-2′-oxocyclohex-3′-en-1′-yl)-acetic acid and its acetate as well as rel-(1′R,4′S,5′R)-2-(1′-farnesyl-4′,5′-dihydroxy-2′-oxocyclohexan-1′-yl)-acetic acid δ-lactone. The structure of an additional isolate, previously described as 2-(1′-farnesyl-2′-hydroxy-5′-oxocyclohex-3′-en-1′-yl)-acetic acid γ-lactone was revised to rel-(1′R,5′R)-2-(1′-farnesyl-5′-hydroxy-2′-oxocyclohex-3′-en-1′-yl)-acetic acid δ-lactone.     

Synthesis and cell growth inhibitory properties of substituted (E)-1-phenylbut-1-en-3-ones

A series of (E)-1-phenylbut-1-en-3-ones, based on the naturally occurring (E)-1-(4′-hydroxyphenyl)but-1-en-3-one [IC₅₀ (K562) 60 μM], was synthesised and screened for cytotoxic activity against the K562 human leukaemia cell line. (E)-1-(Pentafluorophenyl)but-1-en-3-one [IC₅₀ (K562) 1.8 μM] was found to be over 30-fold more active than 1.     

Flavonoids and isoflavonoids of chemotaxonomic significance from Glycyrrhiza pallidiflora (Leguminosae)

Chemical studies were carried out on the root of Glycyrrhiza pallidiflora (Leguminosae), a licorice of no medicinal or commercial value. Two isoflavone glycosides, wistin and ononin, were isolated as major constituents from the methanol extract. A series of chromatographic separations of the acetone extract yielded isoflavone aglycones (afromosin, 2′,7-dihydroxy-4′-methoxyisoflavone and formononetin), flavanones (liquiritigenin and 4′,7-dihydroxy-6,8-diprenylflavanone), an isoflavan [(-)-vestitol], a pterocarpan [(-)-medicarpin], chalcones (echinatin and isoliquiritigenin), dibenzoylmethanes (licodione and 2′-O-methyl-licodione), a flavone (4′,7-dihydroxyflavone), a 3-arylcoumarin (2′-7-dihydroxy-4′-methoxy-3-arylcoumarin), and a new isoflav-3-ene (2′-7-dihydroxy-4′-methoxyisoflav-3-ene). The co-occurrence of the retrochalcone echinatin and the biogenetically related licodione and 2′-O-methyl-licodione is of particular interest, and suggests that this species is closely related to G. echinata and G. inflata. The biogenesis of the retrochalcone is also discussed in relation to its significance in the chemotaxonomy of sects Echinatae and Bucharicae of the genus Glycyrrhiza.     

Neolignans from Ocotea catharinensis

Bark, wood and leaves of Ocotea catharinensis contain respectively 10 (average yield 0.7%.), 15 (average yield 0.004%.) and one (yield 0.4%.) neolignans of the bicyclo[3.2.1]octanoid and the hydrobenzofuranoid structural types, including the new rel-(7S,8R,1′R,4′S,5′R,6′R)-Δ^8′-4′,6′-dihydroxy-5′-methoxy-3,4-methylenedioxy-3′-oxo-8.1′,7.5′-neolignan, (7S,8S)-Δ^{1′,3′,5′,8′}-5,3′,5′-trimethoxy-3,4-methylenedioxy-8.1′,7.O.6′,4.O.7′-neolignan, (7R,8S,1′R,3′R)-Δ^5′,8′-3,4,3′,5′-tetramethoxy-4′-oxo-8.1′,7.O.6′-neolignan and rel-(7R,8S,1′R,2′S)-Δ^4′,8′-2′-hydroxy-3,4-dimethoxy-3′-oxo-8.1′,7.O.2′-neolignan.     

Stereochemistry of the hydrogen abstraction from pyridoxamine phosphate catalyzed by alanine racemase of Bacillus stearothermophilus

Alanine racemase of Bacillus stearothermophilus catalyzes transamination as a side reaction. Stereospecificity for the hydrogen abstraction from C-4′ of pyridoxamine 5′-phosphate occurring in the latter half transamination was examined. Both apo-wild-type and apo-fragmentary alanine racemases abstracted approximately 20 and 80% of tritium from the stereospecifically-labeled (4′S)- and (4′R)-[4′-³H]PMP, respectively, in the presence of pyruvate. Alanine racemase catalyzes the abstraction of both 4′S- and 4′R-hydrogen like amino acid racemase with broad substrate specificity. However, R-isomer preference is a characteristic property of alanine racemase.     

Alkaloids from Heimia salicifolia

Two alkaloids, 9β,2′-dihydroxy-4′′,5′′-dimethoxy-lythran-12-one or 9β-hydroxyvertine (1) and (2S,4S,10R)-4-(3-hydroxy-4-methoxyphenyl)-quinolizidin-2-acetate (2), as well as seven known alkaloids, lythrine (3), dehydrodecodine (4), lythridine (5), vertine (6), heimidine (7), lyfoline (8) and epi-lyfoline (9), were isolated from Heimia salicifolia. The structures of these compounds were elucidated by extensive spectroscopic techniques. Furthermore, the structures of 2, 3, and 6 were confirmed by X-ray crystallography, including absolute configuration determination of 2 and 6. Compounds 6 and 9 showed moderate antimalarial activity.     

Isolation, structural elucidation, and partial synthesis of lutein dehydration products in extracts from human plasma

All-E-(3R,6′R)-3-hydroxy-3′,4′-didehydro-β,γ-carotene (anhydrolutein I) and all-E-(3R,6′R)-3-hydroxy-2′,3′-didehydro-β,ε-carotene (2′,3′-anhydrolutein II) have been isolated and characterized from extracts of human plasma using semipreparative high-performance liquid chromatography (HPLC) on a C₁₈ reversed-phase column. The identification of anhydroluteins was accomplished by comparison of the UV-Vis absorption and mass spectral data as well as HPLC-UV-Vis-mass spectrometry (MS) spiking experiments using fully characterized synthetic compounds. Partial synthesis of anhydroluteins from the reaction of lutein with 2% H₂SO₄ in acetone, in addition to anhydrolutein I (54%) and 2′,3′-anhydrolutein II (19%), also gave (3′R)-3′-hydroxy-3,4-dehydro-β-carotene (3′,4′-anhydrolutein III, 19%). While anhydrolutein I has been shown to be usually accompanied by minute quantities of 2′,3′-anhydrolutein II (ca. 7–10%) in human plasma, 3′,4′-anhydrolutein III has not been detected. The presence of anhydrolutein I and II in human plasma is postulated to be due to acid catalyzed dehydration of the dietary lutein as it passes through the stomach. These anhydroluteins have also been prepared by conversion of lutein diacetate to the corresponding anhydrolutein acetates followed by alkaline hydrolysis. However, under identical acidic conditions, loss of acetic acid from lutein diacetate proceeded at a much slower rate than dehydration of lutein. The structures of the synthetic anhydroluteins, including their absolute configuration at C(3) and C(6′) have been unambiguously established by ¹H NMR and in part by ¹³C NMR, and circular dichroism.     

Synthesis and pharmacology of the isomeric methylheptyl-Δ-tetrahydrocannabinols

The synthesis of the 3-heptyl, and the eleven isomeric 3-methylheptyl-Δ⁸-tetrahydrocannabinols (3–7, R and S methyl epimers, and 8) has been carried out. The synthetic approach entailed the synthesis of substituted resorcinols, which were subjected to acid catalyzed condensation with trans-para-menthadienol to provide the Δ⁸-THC analogue. The 1′-, 2′- and 3′-methylheptyl analogues (3–5) are considerably more potent than Δ⁸-THC. The 4′-, 5′- and 6′-methylheptyl isomers (6–8) are approximately equal in potency to Δ⁸-THC.     

Antimicrobial acylphloroglucinols and dibenzyloxy flavonoids from flowers of Helichrysum gymnocomum

From the dichloromethane extract of the flowers of Helichrysum gymnocomum (Asteraceae) two known flavonoids, 4 and 5, and a known acylphloroglucinol, 3B, were isolated. In addition to 1 and 2, the 4′,6′-dibenzyloxy-2′-hydroxy derivative of 2′,4′,6′-trihydroxychalcone and 5,7-dibenzyloxy derivative of pinocembrin, respectively, are reported in Nature for the first time. A compound 3A, related to 3B has the structure 2-methyl-1-[2,4,6-trihydroxy-3-(2-hydroxy-3-methyl-3-butenyl)phenyl]-1-propanone. Compounds 1, 2, 3A, 3B, 4 and 5 have MIC values below 64 μg/ml against a selection of pathogens, with 3B having the highest sensitivity (6.3–45 μg/ml) for eight of the ten pathogens tested, including Staphylococcus aureus (6.3 μg/ml) and methicillin and gentamycin resistant strain of S. aureus (7.8 μg/ml). With the exception of 2, the other compounds had notable activity (45–63 μg/ml) towards Pseudomonas aeruginosa.     

Synthesis and antibacterial activity of novel neamine derivatives

Synthesis and activity of derivatives at the O5 or O6 positions of 1-N-((S)-4-amino-2-hydroxybutyryl)-3′,4′-dideoxyneamine, which is the neamine moiety of arbekacin, were reported. Among these results, the 5-O-aminoethylaminocarbonyl derivative showed effective activity against Staphylococcus aureus expressing a bifunctional aminoglycoside-modifying enzyme AAC(6′)-APH(2″).     

Methylenedioxy- and methoxyflavones from Melicope coodeana syn. Euodia simplex

Three new natural products, 3,8-dimethoxy-5,7-dihydroxy-3′,4′-methylenedioxyflavone, 3,6,8-trimethoxy-5,7-dihydroxy-3′,4′-methylenedioxyflavone and 3,6,8,3′,4′-pentamethoxy-5,7-dihydroxyflavone were isolated from Melicope coodeana syn. Euodia simplex (Rutaceae) along with 3,6,3′-trimethoxy-5,7,4′-trihydroxyflavone and 3,3′-dimethoxy-5,7,4′-trihydroxyflavone. The structural assignments are based on ¹H and ¹³C NMR data, including discussion of the chemical shifts of C-2 in 3,5-dihydroxy- and 3-methoxy-5-hydroxyflavones. The presence of highly methoxylated and methylenedioxyflavones is characteristic of the genus Melicope, and the present findings support the recent transfer of Euodia simplex to Melicope.     

Design, synthesis and preliminary evaluation of novel 3′-Substituted carboxycyclopropylglycines as antagonists at group 2 metabotropic glutamate receptors

Two novel 3′-substituted carboxycylopropylglycines, (2S,1′S,2′S,3′R)-2-(3′-xanthenylmethyl-2′-carboxycyclopropyl)glycine (8a) and (2S,1′S,2′S,3′R)-2-(3′-xanthenylethyl-2′-carboxycyclopropyl)glycine (8b), were synthesized and evaluated as mGluR ligands. Compound 8b showed to be a potent group II antagonist with submicromolar activity.     

Dihydrochalcones, coumarins and alkaloids from Metrodorea nigra

Two novel dihydrochalcones, 2′,3,4′,6′-tetrahydroxy-4-methoxy-3′,5-di-(3,3-dimethylallyl)-dihydrochalcone and 2′,.3,6′-trihydroxy-4-methoxy-5-(3,3-dimethylallyl)-3′,4′-(2″,2″-dimethyldihydropyran)-dihydrochalcone, have been isolated from fresh fruits of Metrodorea nigra. Stems and leaves showed a similar composition and we have isolated common steroids, simple coumarins, several furocoumarins, furoquinoline alkaloids and a furofuran lignan. From stems, we have also isolated the pentacyclic 6-C-monoterpenyl-5,7-dioxycoumarin, deoxybruceol. Structures of the isolated compounds were elucidated on the basis of spectral data.     

Synthesis and in vitro anti-mycobacterial activity of 5-substituted pyrimidine nucleosides

Mycobacterium tuberculosis and Mycobacterium avium infections cause the two most important mycobacterioses, leading to increased mortality in patients with AIDS. Various 5-substituted 2′-deoxyuridines, uridines, 2′-O-methyluridine, 2′-ribofluoro-2′-deoxyuridines, 3′-substituted-2′,3′-dideoxy uridines, 2′,3′-dideoxyuridines, and 2′,3′-didehydro-2′,3′-dideoxyuridines were synthesized and evaluated for their in vitro inhibitory activity against M. bovis and M. avium. 5-(C-1 Substituted)-2′-deoxyuridine derivatives emerged as potent inhibitors of M. avium (MIC₉₀ = 1–5 μg/mL range). The nature of C-5 substituents in the 2′-deoxyuridine series appeared to be a determinant of anti-mycobacterial activity. This new class of inhibitors could serve as useful compounds for the design and study of new anti-tuberculosis agents.     

Prenylated flavonoids of Erythrina lysistemon grown in Egypt

Three prenylated flavonoid derivatives; 5,7,4′-trihydroxy-8-(3-methylbut-2-enyl)-6-(2″-hydroxy-3″-methylbut-3″enyl) isoflavone (isoerysenegalensein E), 5,7,2′-trihydroxy-4′-methoxy-5′-(3″-methylbut-2″-enyl) isoflavanone (lysisteisoflavanone), 5, 4′-dihydroxy-6-(3-methylbut-2-enyl)-2″-hydroxyisopropyl dihydrofurano [4″,5″:8,7] isoflavone (isosenegalensin), together with the four known flavonoids abyssinone V-4′-methylether, alpinumisoflavone, wighteone and burttinone were isolated from the stem bark of Erythrina lysistemon Hutch. (Leguminosae). Structures were elucidated by spectroscopic methods.     

Five lignan derivatives from in vitro cultures of the liverwort Jamesoniella autumnalis

Five new lignan derivatives, 2,3,6′-tricarboxy-6,7-dihydroxy-1(3′)-2′-pyranonyl-1,2-dihydronaphthalene, its two monomethyl esters, 2,6′-dicarboxy-6,7-dihydroxy-1(3′)-2′-pyranonyl-1,2-dihydronaphthalene and 2,3-dicarboxy-6,7-dihydroxy-1-(3′,4′-dihydroxy)-phenylnaphthalene, were isolated from the methanolic extract of aseptic cultures of the liverwort Jamesoniella autumnalis. Their structures were determined by spectroscopic analysis.     

Two chromones from Peperomia vulcanica

Two chromones: 5-hydroxy-2-(14′-(E)-nonadecenyl) chromone (1) and 5-hydroxy-2-[12′-(3″,4″-methylenedioxyphenyl)dodecanyl] chromone (2), together with six known compounds have been isolated from Peperomia vulcanica Baker & C. H. Wright (Piperaceae). Their structures were determined by spectroscopic analysis including 2D NMR techniques.     

Isoflavonoids from the roots of Erythrina poeppigiana

Five isoflavonoids, 7,4′-dihydroxy-2′-methoxy-8-(γ,γ-dimethylallyl)isoflav-3-ene, 4′-hydroxy-2′-methoxy-6″,6″-dimethylpyran[2″,3″:7,8]isoflav-3-ene, 5,7,4′-trihydroxy-2′-methoxy-5′-(γ,γ-dimethylallyl)isoflavanone, 5,4′-dihydroxy-7,2′-dimethoxy-5′-(γ,γ-dimethylallyl)isoflavanone and 3,9-dihydroxy-4-(γ,γ-dimethylallyl)pterocarpene as well as six known compounds were isolated from the roots of Erythrina poeppigiana. Their structures were established on the basis of spectroscopic evidence.