Three New Myrsinol Diterpenes from <em>Euphorbia prolifera</em> and Their Neuroprotective Activities

Three new myrsinol diterpenes were isolated from the roots of Euphorbia prolifera. Their structures were elucidated as 2α-O-isobutyryl-3β,5α,7β,10,15β-penta-O-acetyl-14α-O-benzoyl-10,18-dihydromyrsinol (1), 2α-O-isobutyryl-3β-O-propion-yl-5α,7β,10,15β-tetra-O-acetyl-10,18-dihydromyrsinol (2), and 2α,14α-di-O-benzoyl-3β,5α,7β,10,15β-penta-O-acetyl-10,18-dihydromyrsinol (3) on the basis of spectroscopic data analyses (IR, ESI-MS, HR-ESI-MS, and 1D and 2D NMR). Their neuroprotective activities were evaluated and compounds 1 and 2 showed neuroprotective effects against MPP⁺-induced neuronal cell death in SH-SY5Y cells.     

Autoxidation of isotachysterol

Isotachysterol, the acid-catalyzed isomerization product of vitamin D₃, produces seven previously unknown oxygenation products in a self-initiated autoxidation reaction under atmospheric oxygen in the dark at ambient temperature. They are (5R)-5,10-epoxy-9,10-secocholesta-6,8(14)-dien-3β-ol (6a), (5S)-5,10-epoxy-9,10-secocholesta-6,8(14)-dien-3β-ol (6b), (10R)-9,10-secocholesta-5,7,14-trien-3β,10-diol (7a), (10S)-9,10-secocholesta-5,7,14-trien-3β,10-diol (7b), (7R,10R)-7,10-epoxy-9,10-secocholesta-5,8(14)-dien-3β-ol (8), 5,10-epidioxyisotachysterol (9) and 3,10-epoxy-5-oxo-5,10-seco-9,10-secocholesta-6,8(14)-dien-10-ol (10). The formation of these products is explained in terms of free radical peroxidation chemistry.     

A new cycloartane triterpenoid from the leaves and stems of Fritillaria hupehensis

A new triterpenoid has been isolated from the leaves and stems of Fritillaria hupehensis Hsiao et K.C.Hsia.Its structure wasestablished as(23Z)-9,19-cycloart-23-ene-3α,25-diol 1 through chemical and spectroscopic studies including 2D NMR.Anotherknown triterpenoid 9,19-cycloart-25-ene-3β,24ξ-diol 2 was also isolated.     

Synthetic transformations of isoquinoline alkaloids. Synthesis of 1-halo derivatives of <Emphasis Type="Italic">endo</Emphasis>-ethenotetrahydrothebaine and their behavior in the heck reaction

Bromination of endo-ethenotetrahydrothebaine derivatives having a pyrrolidine ring fused at the C⁷-C⁸ bond, namely 1′-substituted 4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morphinan-2′,5′-diones, 1′-aryl-4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morphinans, and 4,5α-epoxy-6α,14-etheno-2′α-hydroxy-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morpphinan-5′-one, with molecular bromine in formic acid smoothly afforded the corresponding 1-bromo derivatives. Iodination of 4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]-4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]-morphinan-2′,5′-dione with iodine(I) chloride gave 4,5α-epoxy-6α,14-etheno-1-iodo-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morphinan-2′,5′-dione. The resulting 1-halo derivatives were brought into the Heck reaction with acrylic acid esters to obtain 1-[(E)-2-(alkoxycarbonyl)ethenyl]-substituted compounds. Demethylation of the 6-methoxy group in 1-bromo-endo-ethenotetrahydrothebaines was accomplished using boron(III) bromide in chloroform.     

Ilwensisaponins A,B, C,and D: Triterpene Saponins from Scrophularia ilwensis

From the aerial parts of Scrophularia ilwensis, four new triterpene saponins, ilwensisaponins A–D ( 1 – 4 ) were isolated. The structures of the compounds were elucidated using chemical and spectral data as 13β, 28-epoxy-3-β-{{[β-D -glucopyranosyl-(1→2)]-[α-L -rhamnopyranosyl-(1→4)-β-D -glucopyranosyl-(1→3)]-β-D -fucopyranosyl}-oxy} olean-11-en-23-ol ( 1 ), 3-β-{{[β-D -glucopyranosyl-(1→2)]-[α-L -rhamnopyranosyl-(1→4)-β-D -glucopyranosyl-(1→3)]-β-D -fucopyranosyl}oxy}olena-11, 13(18)-diene-23, 28-diol ( 2 ), 3-β-{{[β-D -glucopyranosyl-(1→2)]-[α-L -rhamnopyranosyl-(1→4)-β-D glucopyranosyl-(1→3)]-β-D fucopyranosyl}oxy}-11α-methoxyolean- 12-ene-23, 28-diol (3) , and 3-β-{{[β-D -glucopyransoyl-(1→2)]-[α-L -rhamnopyranosyl-(1→4)-β-D -glucopyranosyl-(1→3)]-β-D -fucopyranosyl}oxy}olean-12-ene-11α,23,28-triol (4) .     

Transformations of hispanolone. Novel Michael adducts with in planta activity against rice blast

Two novel Michael adducts 9α-cyano-15,16-epoxy-7β-hydroxylabda-13(16),14-dien-6-one (2) and 9α-cyano-15,16-epoxy-7-hydroxylabda-7,13(16),14-trien-6-one (3) and the reduction product of 2, 9α-cyano-15,16-epoxy-6β,7β-dihydroxylabda-13(16),14-diene (4), were synthesized from the naturally occurring labdane diterpene hispanolone (1). Compounds 2-4 exhibited in planta activity against the pathogenic rice blast fungus Magnaporthe grisea.     

Constituents of labiatae—XIV: Vierol and powerol,two new diterpenes from Sideritis canariensis

The two new diterpenes, vierol (1) [(?)kaurane-16α,18-diol] and powerol (3) [(?)kaurane-7β,16α-diol] have been isolated from Sideritis canariensis Ait. 1 was obtained by partial synthesis from epicandicandiol (7), and 3 was related with (?)kauranol (6) and (?)kauren-7β-ol acetate (11). Reduction of the acetoxy-aldehyde 14 by the method of Huang-Minlon and posterior acetylation gave 11, (?)isokauren-7β-ol acetate (17) and (?)kauran-7β-ol acetate (18).     

A taxane with a novel 9α,13α-oxygen bridge from Taxus cuspidata needles

A novel taxane with an unprecedented hemiacetal ring between C-13 and C-9 was isolated from the needles of Taxus cuspidata. The structure was characterized as (12αH)-2α,10β-diacetoxy-5α-cinnamoyloxy-9α,13α-epoxytax-4(20)-ene-11β,13β-diol (1). This is the first example of a natural taxane with a C-13 and C-9 oxygen bridge to form an unusual 6/8/6/6-membered ring system.     

Constituents of Fruit Bodies of Tramete orientalis

A known sterol, 5α,6α-epoxy-5α-crgosta-8(14),22E-diene-3β,7α-diol ( 1 ), and two new sterols, 5α,6α-epoxy-3β,8β,14α-trihydroxy-5α-ergost-22E-en-7-one ( 2 ), (3α,5α),(8β,11β)-diepidioxy-ergost-22E-en-12-one ( 3 ), were isolated and characterized from dried fruit bodies of Trametes orientalis. Their structures were elucidated according to spectral methods.     

Stereoselective ring-opening reactions with AcBr and AcCl. A new method for preparation of some haloconduritols

The actions of AcX (X=Br, Cl) on 7-oxa-bicyclo[2.2.1]hept-5-ene-2,3-diol diacetates and a transoid-epoxide prepared from the acetonide of cyclohexa-3,5-diene-cis-1,2-diol were studied. H₂SO₄-catalyzed cleavage of exo-cis-7-oxa-bicyclo[2.2.1]hept-5-ene-2,3-diol diacetate with AcCl gave (1α,2α,3α,6β)-6-chloro-4-cyclohexene-1,2,3-triol triacetate, from which the corresponding chloroconduritol was obtained by trans-esterification (MeOH/HCl). A similar reaction of the exo-diacetate with AcBr in the presence of H₂SO₄ resulted in bromine addition. The formation of bromine from the reaction of AcBr and H₂SO₄ was observed by independent experiments. H₂SO₄-catalyzed reaction of endo-cis-7-oxa-bicyclo[2.2.1]hept-5-ene-2,3-diol diacetate with AcX (X=Br, Cl) gave (1α,2α,3β,6β)-6-halo-4-cyclohexene-1,2,3-triol triacetates. The reaction of the transoid-epoxide with AcX (X=Br, Cl) with no catalyst gave also (1α,2α,3β,6β)-6-halo-4-cyclohexene-1,2,3-triol triacetates.     

Synthesis, Antigenicity Against Human Sera and Structure-Activity Relationships of Carbohydrate Moieties from <em>Toxocara</em> larvae and Their Analogues

Stereocontrolled syntheses of biotin-labeled oligosaccharide portions containing the Galβ1-3GalNAc core of the TES-glycoprotein antigen obtained from larvae of the parasite Toxocara and their analogues have been accomplished. Trisaccharides Fuc2Meα1-2Gal4Meβ1-3GalNAcα1-OR (A), Fucα1-2Gal4Meβ1-3GalNAcα1-OR (B), Fuc2Meα1-2Galβ1-3GalNAcα1-OR (C), Fucα1-2Galβ1-3GalNAcα1-OR (D) and a disaccharide Fuc2Meα1-2Gal4Meβ1-OR (E) (R = biotinylated probe) were synthesized by block synthesis using 5-(methoxycarbonyl)pentyl-2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl-(1?3)-2-azide-4-O-benzyl-2-deoxy-α-D-galactopyranoside as a common glycosyl acceptor. We examined the antigenicity of these five oligosaccharides by enzyme linked immunosorbent assay (ELISA). Our results demonstrate that the O-methyl groups in these oligosaccharides are important for their antigenicity and the biotinylated oligosaccharides A, B, C and E have high serodiagnostic potential to detect infections caused by Toxocara larvae.     

Practical syntheses of optically active carbagalactose and their potential application to the carbocyclic analogues of KRN7000

Carba-α- and β-d-galactose derivatives were efficiently prepared from a cyclohex-3-ene-1,2-diol derivative 1. Regioselective inversion of 2-OH, and stereoselective dihydroxylation of 1 were accomplished to provide a carba-β-d-galactose derivative 6 in a good yield and with a high stereoselectivity. Stereo-inversion of 1-OH of 6 via oxidation/reduction gave carba-α-d-galactose derivative 12 with a high stereoselectivity. An efficient coupling of carba-α-galactose 12 with an aziridine derivative of sphingosine has been demonstrated to give 1-O-carba-α-galactosyl sphingosine derivative 14.     

Terpenoids—LXXI: Chemical studies of marine invertebrates—XIV. Four representatives of a novel sesquiterpene class—the capnellane skeleton

The isolation and complete structure determination of four marine sesquiterpenoids: Δ⁹⁽¹²⁾-capnellene-8β,10α-diol (1), Δ⁹⁽¹²⁾-capnellene-3β,8β,10α-triol (3), Δ⁹⁽¹²⁾-capnellene-5α,8β,10α-triol (5), Δ⁹⁽¹²⁾-capnellene-2ξ,8β,10α-triol (7) from the soft coral Capnella imbricata is described. These alcohols are the first members of a fundamentally new sesquiterpene class consisting of three 5-membered fused rings which we have named capnellane (A).     

Officinatrione: an unusual (17S)-17,18-seco-lupane skeleton,and four novel lupane-type triterpenoids from the roots of Taraxacum officinale

Novel 5 lupane-type of triterpenois, i.e., 3β-acetoxy-18α,19α-epoxylupan-21β-ol (1), 18α,19α-epoxy-21β-hydroxylupan-3-one (2), lup-18-ene-3,21-dione (3), lupa-18,21-dien-3β-yl acetate (4), and (17S)-17,18-seco-lup-19(21)-ene-3,18,22-trione (5), named officinatrione, as well as 16 known compounds from the roots of Taraxacum officinale collected in Takatsuki city, Osaka, Japan. Of the above compounds, 5 was the first lupane-type triterpene, of which the D-ring was open to form a nine-membered ring. Compounds 2 and 5 exhibited moderate cytotoxic activities against L1210 cell line (IC₅₀ 10.5 and 10.1 μM).     

Specific oxidation of C-14 oxygenated 4(20),11-taxadienes by microbial transformation

Three C-14 oxygenated taxanes, 2α,5α,10β,14β-tetraacetoxytaxa-4(20),11-diene (1), 2α,5α,10β-triacetoxy-14β-(2-methylbutyryloxy)taxa-4(20),11-diene (2), and yunanaxane (3), major products of callus cultures of Taxus spp., were regio- and stereoselectively hydroxylated at the 7β position by a fungus, Absidia coerulea IFO 4011. Intriguingly, when 1 was co-administered with β-cyclodextrin and incubated with the fungus cell cultures, three other compounds 5α,9α,10β,13α-tetraacetoxytaxa-4(20),11-dien-14β-ol (7), 5α,9α,10β,13α-tetraacetoxytaxa-4(20),11-dien-1β-ol (8) and 5α,9α,10β,13α-tetraacetoxy-11(15→1) abeotaxa-4(20),11-dien-15-ol (9) were obtained.     

Tetracyclic triterpenoids isolated from semi-mangrove plant Hibiscus tiliaceus

A continuing phytochemical study on the semi-mangrove plant Hibiscus tiliaceus yielded two new tetracyclic triterpenoids （3β,24S）-19（10→9）-abeo-8α,9β,10α-eupha-5,25（26）-dien-3,24-diol （tiliacol A, 1 ）, and （3β,23Z）-19（10→9）-abeo-8α,9β,10α-tircalla-5,23-dien-3,25-diol （tiliacol B, 3）, together with one known analog （2）. Their structures were elucidated on the basis of extensive spectral analyses （MS, IR, 1D NMR and 2D NMR） and comparison with literature compounds. Compound 2 showed potent cytotoxicity against both P388 and HeLa cells with ICon values of 11.2 μmol/L and 11.5 μmol/L, resoectively.     

Photochemical transformation leading to eupteleogenin—I: Introduction of epoxy-lactone system

Being interested in the photochemical reactions which are potentially applied in the biogenetic-type chemical derivations of natural products, the appropriate photochemical means have been sought to produce the 11α,12α-epoxy-13β,28-lactone moiety in the oleanane skeleton, which is one of the unique functions of eupteleogenin (2). Photooxidation of oleanolic acid (6a) in acidic medium has been undertaken and desired 11α,12α-epoxy-oleanolic lactone (12a) obtained. Erythrodiol (8a) has been submitted to photooxidation and the 11α,12α-epoxy-13β,28-oxide moiety (24a) introduced along with skeletal rearrangement affording the 11α,12α-epoxy-taraxerene derivative (25a). During photooxidation of 8a, it has been noticed that 11ξ-hydroxy-olean-12-ene derivatives (28, 42) are fairly labile, allowing the trans-formation of dihydropriverogenin A(10a) into the thermodynamically less favored isomer priverogenin B(9).     

Novel Nor and Seco Triterpenoids from Koelpinia linearis

Three novel triterpenoids, C:D seco (8→14) urso-8(26),12(13)-dien-3β-ol, C:D seco (8→14) urso-8(26),13(14)-dien-3β-ol, and C:Dseco (8→14),27 nor-urso-12-ene-3β-20α-diol were isolated from Koelpinia linearis and characterized by spectral and chemical methods.     

Cytotoxic Podophyllotoxin Type-Lignans from the Steam Bark of <em>Bursera fagaroides </em>var. <em>fagaroides</em>

The hydroalcoholic extract of the steam bark of B. fagaroides var. fagaroides displayed potent cytotoxic activity against four cancer cell lines, namely KB (ED₅₀ = 9.6 × 10^-2 μg/mL), PC-3 (ED₅₀ = 2.5 × 10^-1 μg/mL), MCF-7 (ED₅₀ = 6.6 μg/mL), and HF-6 (ED₅₀ = 7.1 × 10^-3 μg/mL). This extract also showed anti-tumour activity when assayed on mice inoculated with L5178Y lymphoma cells. Bioactivity-directed isolation of this extract, afforded seven podophyllotoxin-type lignans identified as podophyllotoxin (1), β-peltatin-A-methylether (2), 5'-desmethoxy-β-peltatin-A-methylether (3), desmethoxy-yatein (4), desoxypodophyllotoxin (5), burseranin (6), and acetyl podophyllotoxin (7) by 1D and 2DNMR and FAB-MS analyses, and comparison with reported values. All the isolated compounds showed potent cytotoxic activity in the cell lines tested, especially compound 3, which exhibited greater activity than camptothecin and podophyllotoxin against PC-3 (ED₅₀ = 1.0 × 10^-5 μg/mL), and KB (ED₅₀ = 1.0 × 10^-5 μg/mL). This is the first report of the isolation of podophyllotoxin and its acetate in a Bursera species.     

Two New Compounds Isolated from<em> Liriope muscari</em>

Two new compounds, (2S,3R)-methyl 7-hydroxy-2-(4-hydroxy-3-methoxy-phenyl)-3-(hydroxymethyl)-2,3-dihydrobenzofuran-5-carboxylate (1) and (4R,5S)-5-(3-hydroxy-2,6-dimethylphenyl)-4-isopropyldihydrofuran-2-one (2), tentatively named norcurlignan and limlactone, respectively, were isolated from Liriope muscari, together with the known compound (-)-pinoresinol (3). The structures of these compounds were elucidated and characterized on the basis of 1D NMR, 2D NMR, CD and MS data. The in vitro antioxidant activities of compounds 1-3 were assessed by the DPPH and ABTS scavenging methods.