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.     

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.     

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.     

4-Arylcoumarins from Coutarea hexandra

Four new 4-arylcoumarins have been isolated from Coutarea hexandra and their structures established as 5,7,4′-trimethoxy-4-phenylcoumarin, 4′-hydroxy-5,7-dimethoxy-4-phenylcoumarin, 3′-hydroxy-5,7-4′-trimethoxy-4-phenylcoumarin and 3′,4′-dihydroxy-5,7-dimethoxy-4-phenylcoumarin.     

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.     

Chalconoid and stilbenoid glycosides from Guibourtia tessmanii

Phytochemical studies on the stem bark of Guibourtia tessmanii yielded a dihydrochalcone glucoside, 2′,4-dihydroxy-4′-methoxy-6′-O-β-glucopyranoside dihydrochalcone and a new stilbene glycoside, 3,5-dimethoxy-4′-O-(β-rhamnopyranosyl-(1→6)-β- glucopyranoside) stilbene besides the known pterostilbene. Their structures were established on the basis of one and two dimensional NMR spectroscopic techniques, FABMS and chemical evidence.     

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.     

Synthesis of a tetracyclic, conformationally constrained analogue of Δ-THC

A tetracyclic, conformationally constrained analogue of Δ⁸-THC (2) has been synthesized in which a two carbon bridge exists between C2 and C2′. Two conceptually related syntheses of 2 are described, both of which employ 5,7-dimethoxy-4-oxo-1,2,3,4-tetrahydronaphthoic acid (11) as starting material. This substrate was converted to 5,7-dimethoxy-2-propyl-1,2,3,4-tetrahydronaphthalene (7) and its 4-keto derivative (18). Demethylation of 11 and 18 provided the corresponding resorcinols, which were condensed with trans-p-menthadienol to afford cannabinoid 2, and a keto derivative (20). LiAlH₄/AlCl₃ reduction of 20 provided 2. Cannabinoid 2 has relatively low affinity for the cannabinoid brain receptor (K_i = 703 ± 98nM).     

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.     

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.     

Studies of the cation complexing ability of crowns Part I. Synthesis, characterization and crystal structure of diazacrowns and their barium complexes

A number of N,N′-bis(4-substituted phenyl)-1,7-diaza-12-crown-4 and N,N′-bis(4-substituted phenyl)-1, 10-diaza-18-crown-6 (where the substituents are OCH₃, CH₃, H, Cl, respectively) have been prepared by cyclization reaction of a ditosylate with the appropriately substituted diol. These new macrocyclic ligands have been characterized by means of elemental analysis, IR, ¹H NMR and MS spectra. The crystal structures of N,N′-bis(4-chlorophenyl)-1,10-diaza-18-crown-6 (21) and its complex with barium thiocyanate Ba(SCN)₂ (22) have been determined by single crystal X-ray diffraction. The crystallographic data are as follows: 21: C₂₄H₃₂Cl₂N₂O₄, orthorhombic, P2₁2₁2₁, A=4.852(1), B=11.989(2), C=41.231(8) Å, V=2398.7(8) ų, Z=4; 22: C₂₆H₃₂Cl₂N₄O₄S₂Ba, monoclinic, P2₁/c, A=8.801(2), B=11.653(9), C=15.756(6) Å, ß=105.96(3)°, V=1553.7(14) ų, Z=2. In the complex, the Ba atom is eight-coordinate (O(1), O(2), O(1)′, O(2)′, N(1), N(1)′, N(21), N(21)′) to form a distorted D_6h geometry with the Ba atom at the center of crystallographic symmetry.     

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.     

Three highly oxygenated flavone glucuronides in leaves of Spinacia oleracea

Droplet counter-current chromatographic separation and subsequent TLC demonstrated the existence of at least 14 phenolics in the leaves of Spinacia oleracea. Three have now been isolated and identified, respectively, as the 4′-glucuronides of 5,7,4'-trihydroxy-3,6,3′-trimethoxyflavone (jaceidin), 5,3′,4′-trihydroxy-3-methoxy-6:7-methylene-dioxyflavone and 5,4′-dihydroxy-3,3′-dimethoxy-6:7-methylenedioxyflavone.     

Synthesis of 4′-methoxyadenosine and related compounds

Addition of iodine and methanol to N⁶,N⁶-dibenzoyl-9(2,3-O-carbonyl-5-deoxy-β-d-erythro-pent-4-enofuranosyl)adenine (4) selectively gives N⁶,N⁶-dibenzoyl-2′,3′-O-carbonyl-5′-deoxy-5′-iodo-4′-methoxyadenosine (5). Compound 5 can be converted into 4′-methoxyadenosine via hydrolysis of the carbonate followed by benzoylation, displacement of the 5′-iodo function by benzoate ion, and hydrolysis with ammonia. Configurational assignments are based upon comparisons of ¹H- and ¹³C-n.m.r. spectra with those of previously characterised analogues in the uracil series and by borate electrophoresis. Intermediates in the above scheme have also been converted into 5′-amino-5′-deoxy-4′-methoxyadenosine, 4′-methoxy-5′-O-sulfamoyladenosine, and ethyl 4′-methoxyadenosine-5′-carboxylate, each of which is a 4′-methoxy analogue of biologically active derivatives of adenosine.     

Chemical synthesis of an artificial antigen containing the trisaccharide hapten of Mycobacterium leprae

The crystal and the molecular structure of 4,1′,6′-trichloro-4,1′,6′-trideoxy-galacto-sucrose (TGS) was determined by X-ray analysis at 294 K. Crystals of TGS are orthorhombic, space group P2₁2₁2₁, with a = 7.318(3), b = 12.027(4), c = 18.136(5) Å, V = 1596(1) ų, Z = 4; D_x = 1.655 g.cm^-3, λ(MoK) = 0.71073 Å, μ(MoK) = 5.44 cm^-1, F(000) = 816. The X-ray intensities of 2649 reflections with I 2.5σ(I) were measured with Zr-filtered MoK-radiation. The structure was solved by the Patterson procedure and refined by full-matrix least-squares to a final R-value of 0.0298. Large conformational differences between TGS and sucrose were observed, particularly in the conformation of the glycosidic linkage. These differences originate from chlorine substitution, which affects intramolecular hydrogen bonding and sweet-taste glucophores.     

Isolation and X-ray structure determination of a neolignan from Clerodendron inerme seeds

A new neolignan, 5,8-epoxy-6,7-dimethyl 2′,3′,2″,3″-dimethylene dioxy-4′,1″-dimethoxy-1,2:3,4-dibenzo-1,3-cyclooctadiene, from the petrol extract of Clerodendron inerme seeds, was characterized by spectroscopic and X-ray crystallographic methods. This compound makes up ca 5% by wt of the seeds.     

Effects of electronic structure on chiral induction in outer-sphere electron transfer reactions of complexes with the C3 symmetric ligand, 1,4,7-triazacyclononane-1,4,7-tris[2′(R)-2′-propionate](-3)

The ligand 1,4,7-triazacyclononane-1,4,7-tris[2′(R)-2′-propionate](-3)((R)-tacntp³⁻), binds stereospecifically to transition metal ions. The structures of the complexes [Cr((R)-tacntp)]·NaBr and [Fe((R)-tacntp)]·H₂O have been determined by X-ray crystallography. Both complexes have the Λ-configuration but the conformation of the chelate rings in Λ-[Cr((R)-tacntp)] is (λ,λ,λ) with a geometry close to octahedral while in Λ-[Fe((R)-tacntp)] it is (δ,δ,δ) and the geometry is closer to that of a trigonal prism. Chiral induction in the electron transfer reactions of Λ-[Co((R)-tacntp)], Λ-[Fe((R)-tacntp)] and Λ-[Mn((R)-tacntp)] with [Co((RR,SS)-chxn)₃]²⁺ has been investigated. All three reactions are outer-sphere and four isomeric [Co((RR,SS)-chxn)₃]³⁺ products are identified in each case. The oxidants Λ-[Fe((R)-tacntp)] and Λ-[Mn((R)-tacntp)] show very similar selectivities, quite different from those of Λ-[Co((R)-tacntp)]. Reasons for this behavior are discussed.     

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.     

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.     

Investigations into the biosynthetic pathways for classical and ring B-unsaturated oestrogens in equine placental preparations and allantochorionic tissues

In on-going studies of ‘classical’ and ring B-unsaturated oestrogens in equine pregnancy, the products of metabolism of [2,2,4,6,6-²H₅]-testosterone and [16,16,17-²H₃]-5,7-androstadiene-3β,17β-diol with equine placental subcellular preparations and allantochorionic villi have been identified. Using mixtures of unlabelled and [²H]-labelled steroid substrates has allowed the unequivocal identification of metabolites by twin-ion monitoring in gas chromatography–mass spectrometry (GC–MS). Two types of incubation were used: (i) static in vitro and (ii) dynamic in vitro. The latter involved the use of the Oxycell™ cartridge (Integra Bioscience Systems, St Albans, UK) whereby the tissue preparation was continuously supplied with supporting medium plus appropriate cofactors in the presence of uniform oxygenation. [²H₅]-Testosterone was converted into [²H₄]-oestradiol-17β, [²H₄]-oestrone and [²H₃]-6-dehydro-oestradiol-17 in both placental and chorionic villi preparations, but to a greater extent in the latter, confirming the importance of the chorionic villi in oestrogen production in the horse.

On the basis of GC–MS characteristics (M⁺ m/z 477/482 (as O-methyl oxime-trimethyl silyl ether), evidence for 19-hydroxylation of testosterone was found in static incubations, while the presence of a 6-hydroxy-oestradiol-17 was recorded in dynamic incubations (twin peaks in the mass spectrum at m/z 504/507, the molecular ion M⁺). It was not possible to determine the configuration at C-6. The formation of small, but significant, quantities of [²H₄]-17β-dihydroequilin was also shown, and a biosynthetic pathway is proposed.

In static incubations of placental microsomal fractions, the 17β-dihydro forms of both equilin and equilenin were shown to be major metabolites of [²H₃]-5,7-androstadiene-3,17-diol. Using static incubations of chorionic villi, the deuterated substrate was converted into the 17β-dihydro forms of both equilin and equilenin, together with an unidentified metabolite (base peak, m/z 504/506). The isomeric 17-dihydroequilins were also obtained using the dynamic in vitro incubation of equine chorionic villi, together with the 17β-isomer of dihydroequilenin. Confirmation of the identity of 17β-dihydroequilin and 17β-dihydroequilenin was obtained by co-injection of the authentic unlabelled steroids with the phenolic fraction obtained from various incubations. Increases in the peak areas for the non-deuterated steroids (ions at m/z 414 (17β-dihydroequilin) and 412 (17β-dihydroequilenin) (both as bis-trimethyl silyl ether derivatives) were observed. Biosynthetic pathways for formation of the ring B-unsaturated oestrogens from 5,7-androstadiene-3β,17β-diol are proposed.