Evaluation of the antiviral and antimicrobial activities of triterpenes isolated from Euphorbia segetalis

A phytochemical reinvestigation of the whole plant of Euphorbia segetalis yielded five tetracyclic triterpenes: 3beta-hydroxy-cycloart-25-en-24-one (1), cycloart-25-ene-3beta,24-diol (2), cycloart-23-ene-3beta,25-diol (3), lanosta-7,9(11),24-trien-3beta-ol (4) and lanosta-7,9(11),24(31)-trien-3beta-ol (5). beta-acetoxy-cycloart-25-en-24-one (1a) and glutinol (6), lupenone (7), dammaranodienol (9), cycloartenol acetate (10), 24-methylenecycloartanol acetate (11) and beta-sitosterol (12), isolated previously, were evaluated for their antiviral activities against Herpes simplex virus (HSV) and African swine fever virus (ASFV). Lupenone exhibited strong viral plaque inhibitory effect against HSV-1 and HSV-2. The in vitro antifungal and antibacterial activities of la, cycloart-23-ene-3beta,25-diol, 3-acetate (3a) and 6-12 were also investigated.     

Cycloartane triterpenes from Euphorbia tuckeyana

Investigation of the acetone extract of the whole plant of Euphorbia tuckeyana afforded a new cycloartane-type triterpene named as cyclotucanol. Its structure was established as cycloartane-24-methylene-3beta,25-diol (1). The known cycloartane triterpenes cycloeucalenol (2), 3beta-hydroxycycloart-25-en-24-one (3), cycloart-25-ene-3beta,24-diol (4), 25,26,27-trisnor-3beta-hydroxycycloartan-24-al (5) and cycloart-23-ene-3beta,25-diol (6) were also isolated and identified.     

Five new sesquiterpenoids and a new diterpenoid from Erigeron annuus (L.) PERS., Erigeron philadelphicus L. and Erigeron sumatrensis RETZ

The aerial parts of Erigeron annuus (L.) PERS., E. philadelphicus L. and E. sumatrensis RETZ. (Compositae) have been investigated chemically. A new sesquiterpenoid, 6beta,14-epoxyeudesm-4(15)-en-1beta-ol (1), and a new diterpenoid, philadelphinone (6), have been isolated from E. philadelphicus. Four new sesquiterpenoids, (7R*)-opposit-4(15)-ene-1beta,7-diol (2), 11-methoxyopposit-4(15)-en-1beta-ol (3), 15-methoxyisodauc-3-ene-1beta,5alpha-diol (4) and 10alpha-hydroxycadin-4-en-15-al (5), have been isolated from E. annuus. Compounds 2 and 4 were also isolated from E. sumatrensis. The structures of the new compounds were elucidated on the basis of their spectral data.     

Megastigmane glucosides from Equisetum debile and E. diffusum

A new megastigmane diglucoside, (3S,5R,6S,7E,9S)-megastigman-7-ene-5,6-epoxy-3,9-diol 3,9-O-beta-D-diglucopyranoside (3), was isolated from the aerial portion of Equisetum debile along with macarangioside D (debiloside A), sammangaoside A, (6R,9S)-3-oxo-alpha-ionol 9-O-beta-D-glucopyranoside, debiloside B, kaempferol 3-O-sophoroside, kaempferol 3,7-O-beta-D-diglucopyranoside, kaempferol 3-O-sophoroside-7-O-beta-D-glucopyranoside, phenylethyl O-beta-D-glucopyranoside, (Z)-3-hexenyl O-beta-D-glucopyranoside, (7S,8R)-dehydrodiconiferyl 4-O-beta-D-glucopyranoside, and L-tryptophan. The absolute configuration at C-6 of the original structure of debilo-side A was revised to 6R-configuration, and was identical with macarangioside D (1). From the aerial portion of E. diffusum, four compounds, sammangaoside A, kaempferol 3-O-sophoroside and L-tryptophan and (3S,5R,6S,7E,9S)-megastigman-7-ene-5,6-epoxy-3,9-diol 3-O-beta-D-glucopyranoside were identified. The spectroscopic data of (3S,5R,6S,7E,9S)-megastigman-7-ene-5,6-epoxy-3,9-diol 3-O-beta-D-glucopyranoside (13) were found to be identical with corchoionoside A (9R-isomeric compound). The structure of corchoionoside A was also discussed. Structure determinations were based on physical data and spectroscopic evidence.     

Beyerane derivatives and a sesquiterpene dimer from Japanese Cypress (Chamaecyparis obtusa)

In the course of studies on biological active constituents from woody plants, we previously reported the isolation of many lignan derivatives as neurite outgrowth-promoting compounds from an ethyl acetate soluble fraction of Japanese Cypress (Chamaecyparis obtusa). Further chemical investigation on the residual parts of the ethyl acetate soluble fraction of a methanol extract of Japanese Cypress resulted in the isolation of four new beyerene type derivatives and a novel sesquiterpene dimer formed between cryptomeridiol and hinokiic acid. Their structures were elucidated as 18-O-(Z)-p-coumaroylbeyer-15-ene-18-ol (1), 18-O-(E)-p-coumaroylbeyer-15-ene-18-ol (2), 18-O-(E)-p-coumaroylbeyer-15-ene-11beta,18-diol (3), 18-O-(Z)-p-coumaroylbeyer-15-ene-11beta,18-diol (4) and ent-cryptomeridiol-4-yl-hinokiiate (5) by (1)H-NMR, (13)C-NMR, 2D-NMR, and HR-MS spectral analysis.     

Structural revision of terpenoids with a (3Z)-2-methyl-3-penten-2-ol moiety by the synthesis of (23E)- and (23Z)-cycloart-23-ene-3beta,25-diols

Synthesis of (23E)-cycloart-23-ene-3beta,25-diol (1) and its 23Z-isomer 2 was achieved by using cycloartenol as a starting material, thus revising the proposed structure of natural 2 to 1 unequivocally. These synthetic studies revealed that the structural revision (Z-form --> E-form) should also be applied to terpenoids such as (23Z)-3beta-acetoxyeupha-7,23-diene-25-ol, (23Z)-tirucalla-7,23-diene-3beta,25-diol, quadrangularol A, quadrangularic acid K, and daurichromene C.     

Studies on the constituents of Cimicifuga species. XXVIII. Cycloart-7-enol glycosides from the underground parts of Cimicifuga simplex Wormsk

Four new cycloart-7-ene triterpenol arabinosides, bugbanosides C-F, were isolated from the underground parts of Cimicifuga simplex Wormsk. (Ranunculaceae). The structures were elucidated as 12beta-acetoxy-3beta,15alpha,-24R,25-tetrahydroxy-16,23-dione-cycloart-7-ene 3-O-alpha-arabinopyranoside, 12beta-acetoxy-24R,25-epoxy-3beta,15alpha-dihydroxy-16,23-dione-cycloart-7-ene 3-O-alpha-L-arabinopyranoside, 12beta-acetoxy-24R,25-epoxy-3beta-hydroxy-16,23-dione-cycloart-7-ene 3-O-alpha-L-arabinopyranoside, and 16,23R:16,24S-diepoxy-3beta,12beta,15alpha,25-tetrahydroxy-cycloart-7-ene 3-O-alpha-L-arabinopyranoside on the basis of spectral and chemical evidence. The circular dichroism (CD) of bugbanosides C-F showed strong negative maxima at 214-217 nm due to a cycloart-7-ene system, as well as other cycloart-7-ene triterpenes. The CD data showed to be useful in determining basic skeletons, including absolute stereostructures of cycloart-7-ene triterpenes.     

Total synthesis of methyl protodioscin: a potent agent with antitumor activity

Methyl protodioscin (1), otherwise known as 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->4)]-beta-d-glucopyranosyl]-26-O-[beta-D-glucopyranosyl]-22-methoxy-25(R)-furost-5-ene-3 beta,26-diol, has been synthesized for the first time from diosgenin through nine steps in an overall yield of 7.8%.     

New sphingolipids and a sterol from a lobophytum species of the Indian ocean

Chemical investigation of a soft coral species of the genus Lobophytum has resulted in the isolation of three new sphingolipids--(2S,3S,4R)-2-nonadecanoylamino-octadecane-1,3,4-triol (1), (2S,3R,4E,8E)-[(2'R)-2'-hydroxyheptadecanoylamino]-4,8-octadecadiene-1,3-diol (2), 1-O-(beta-D-glucopyranosyl)-(2S,3R,4E,8E)-2-[(2'R)-2'-hydroxynonadecanoylamino]-9-methyl-4,8-octadecadiene-1,3-diol (3) and a sterol--(24S)-ergost-5-en-3beta,7beta-diol (4) along with the known sphingolipid--(2S,3R,4E,8E)-2-hexadecanoylamino-4,8-octadecadien-1,3-diol (5) which showed cytotoxicity against human peripheral blood mononuclear cells (PBMC).     

A new pyrrolidine derivative and steroids from an algicolous Gibberella zeae strain

A new pyrrolidine derivative, 3-hydroxy-5-(hydroxymethyl)-4-(4'-hydroxyphenoxy)pyrrolidin-2-one (1), and eight known steroids, (22E,24R)-7beta,8beta-epoxy-3beta,5alpha,9alpha-trihydroxyergosta-22-en-6-one (2, a reassigned structure of (22E,24R)-5alpha,6alpha-epoxy-3beta,8beta,14alpha-trihydroxyergosta-22-en-7-one), (22E,24R)-3beta,5alpha,9alpha-trihydroxyergosta-7,22-dien-6-one (3), (22E,24R)-3beta,5alpha-dihydroxyergosta-7,22-dien-6-one (4), (22E,24R)-ergosta-7,22-dien-3beta/,5alpha,6beta-triol (5), (22E,24R)-ergosta-5,22-dien-3beta-ol (6), (22E,24R)-5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol (7), (22E,24R)-5alpha,8alpha-epidioxyergosta-6,9(11),22-trien-3beta-ol (8), and (22E,24R)-1(10 --> 6)-abeo-ergosta-5,7,9,22-tetraen-3alpha-ol (9), were isolated from the cultures of Gibberella zeae, an endophytic fungus isolated from the marine green alga Codium fragile. Their structures and relative stereochemistry were elucidated by 1D, 2D NMR and mass spectroscopic techniques. Compound 1 showed cytotoxicity against A-549 and BEL-7402 cell lines.     

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.     

Chemical constituents from Aphanamixis grandifolia

(23E)-25-Methylcycloart-23-en-3β-ol (1), a cycloartane-type triterpenoid featuring an unusual skeleton of 31 carbon atoms, (17E)-cycloart-17,26-dien-3β-ol (2), a new cycloartane-type triterpenoid, and the other two new compounds 4R-hydroxy-4-(9S-hydroxy-12-methylhexan-6-yl)-3-methylcyclopent-2-enone (6) and 7-hydroxy-5-(2'-hydroxy-4',5'-dimethoxyphenyl)-2-methoxy-6-methyl-1,4-naphthoquinone (7), together with three known cycloart-3β-ol triterpenoids (3-5) were isolated from aerial parts of Aphanamixis grandifolia. Their structures were elucidated by spectroscopic analysis, and that of 1 was confirmed by single-crystal X-ray diffraction. The absolute configuration of two carbon stereocenters of compound 6 was determined to be 4R,9S by means of circular dichroism (CD) and auxiliary chiral α-methoxy-α-(trifluoromethyl)phenylacetic acid (MTPA) derivatives, respectively. The compound 3 exhibited significant cytotoxicities against HL-60, Hep G2 and HeLa, and compounds 1, 2, 5, 6 and 7 exhibited modest cytotoxicities. No activity of compound 4 could be due to the absence of the hydroxyl group at C-24.     

Six new dammarane-type triterpene saponins from the leaves of Panax ginseng

Six new minor saponins, together with known ginsenosides, were isolated from the leaves of Panax ginseng. The new saponins were named as ginsenoside-Rh5, -Rh6, -Rh7 -Rh8, -Rh9 and -Rg7, and their structures were elucidated on the basis of chemical and physicochemical evidence to be as follows: ginsenoside-Rh5: 3beta,6alpha,12beta,24zeta-tetrahydroxy-dammar-20(22),25-diene 6-O-beta-D-glucopyranoside (1), -Rh6: 3beta,6alpha12beta,20(S)-tetrahydroxy-25-hydroperoxy-dammar-23-ene 20-O-beta-D-glucopyranoside (2), -Rh7: 3beta,7beta,12beta,20(S)-tetrahydroxy-dammar-5,24-diene 20-O-beta-D-glucopyranoside (3), -Rh8: 3beta,6alpha,20(S)-trihydroxy-dammar-24-ene-12-one 20-O-beta-D-glucopyranoside (4), -Rh9: 3beta,6alpha,20(S)-trihydroxy-12beta,23-epoxy-dammar-24-ene 20-O-beta-D-glucopyranoside (5) and -Rg7: 3-O-beta-D-glucopyranosyl 3beta,12beta,20(S),24(R)-tetrahydroxy-dammar-25-ene 20-O-beta-D-glucopyranoside (6).     

A new pentanorlanostane derivative, cladosporide A, as a characteristic antifungal agent against Aspergillus fumigatus, isolated from Cladosporium sp

In the course of searching for new antifungal agents, a new pentanorlanostane derivative, cladosporide A (1), was isolated along with ergosterol, ergosterol peroxide and 23,24,25,26,27-pentanorlanost-8-ene-3beta,22-diol (2) from Cladosporium sp. as a characteristic antifungal agent against the human pathogenic filamentous fungus Aspergillus fumigatus. The structure of 1 was established as 3beta,22-dihydroxy-23,24,25,26,27-pentanorlanostane-29-al by spectroscopic and chemical investigation and X-ray crystallographic analysis. Inhibitory activity against A. fumigatus (IC80 0.5-4.0 microg/ml) was observed for cladosporide A (1), but no activity was observed against pathogenic yeasts, Candida albicans and Cryptococcus neoformans, and other pathogenic filamentous fungi, Aspergillus niger and A. flavus. The 4beta-aldehyde residue in 1 might be essential for the antifungal activity, since 23,24,25,26,27-pentanorlanost-8-ene-3beta,22-diol (2) showed no inhibition against the above four fungi.     

The Terpenoids of Maytenus boaria MOL. (Celastraceae)

The known triterpenoids β-amyrin (= olean-12-en-3β-ol; 22 ), lupeol (= lup-20(29)-en-3β-ol; 17 ), betulin (= lup-20(29)-ene-3β,28-diol; 18 ), lup-20(29)-ene-3β,30-diol ( 20 ), oleanolic acid (= 3β-hydroxyolean-12-en-28-oic acid; 21 ), and betulonic acid (= 3-oxolup-20(29)-en-28-oic acid; 19 ), together with epicatechol (= cis-2-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3,5,7-triol; 23 ), 5′-O-methylgallocatechol (= trans-2-(3,4-dihydroxy-5-methoxyphenyl)-3,4-dihydro-2H-1-benzopyran-3,5,7-triol; 24 ), and 4-hydroxybenzaldehyde were isolated from the aerial parts of Maytenus boaria (MOL. ). Additonally, the eight 4,C⁴-dihydro-β-agarofuran sesquiterpenoids 1–8 , one of them a diol with a (4R)-configuration, and compound 9 were present in the extract. The structures of these compounds were established by spectroscopic and chemical means.     

Ceramide constituents from five mushrooms

Five mushrooms, Panellus serotinus, Lyophyllum connatum, Amanita pantherina, Sarcodon aspratus and Lepista nuda, have been investigated chemically. Two new ceramides, (2S,3R,4E,8E)-N-hexadecanoyl-2-amino-9-methyl-4,8-octadecadiene-1,3-diol (1) and (2S,3R,4E,8E,9'Z,12'Z)-N-9',12'-octadecadienoyl-2-amino-9-methyl-4,8-octadecadiene-1,3-diol (2), have been isolated from Panellus serotinus. Compound 2 was also isolated from Lyophyllum connatum. Two new ceramides, (2S,2'R,3R,4E,8E)-N-2'-hydroxypentadecanoyl-2-amino-9-methyl-4,8-octadecadiene-1,3-diol (4) and (2S,2'R,3R,4E,8E)-N-2'-hydroxytetradecanoyl-2-amino-9-methyl-4,8-octadeca-diene-1,3-diol (5), have been isolated from Amanita pantherina with (2S,2'R,3R,4E,8E)-N-2'-hydroxyhexadecanoyl-2-amino-9-methyl-4,8-octadecadiene-1,3-diol (3), a known synthetic compound. Compounds 3 and 4 were also isolated from Sarcodon aspratus and compound 3 was isolated from Lepista nuda. The structures of the new compounds were elucidated on the basis of their spectral data.     

Complete assignments of 1H and 13C NMR spectral data for three new triterpenoid saponins from Ilex hainanensis Merr

Three new oleanane-type triterpenoid saponins, ilexhainanoside C, D and E, all with 24, 28-dioic acid groups, were isolated from the leaves of Ilex hainanensis. They were 3beta-hydroxyolean-12-ene-24, 28-dioic acid-28-O-beta-D-glucopyranoside(1), 3beta, 19alpha-dihydroxyolean-12-ene-24, 28-dioic acid-28-O-beta-D-glucopyranoside(2) and 3beta, 29-dihydroxyolean-12-ene-24, 28-dioic acid-28-O-beta-D-glucopyranoside(3). The structures of these three new compounds were elucidated and complete assignments of the (1)H and (13)C NMR spectroscopic data were achieved by 1D and 2D NMR experiments [heteronuclear single quantum coherence (HSQC), HMBC and rotational nuclear Overhauser effect spectroscopy (ROESY)].     

Synthesis of the aglycone of the shark repellent pavoninin-4 using remote functionalization

[reaction: see text] The aglycone of shark repellent pavoninin-4, (25R)-5alpha-cholestan-3alpha,15alpha,26-triol 26-acetate 1a, was synthesized from (25R)-cholest-5-en-3beta,26-diol 4 (26-hydroxycholesterol) in eight steps in 18% overall yield. Breslow's remote functionalization strategy was used as a key step to introduce the C-15alpha alcohol on a steroid D ring. An efficient synthesis of the 26-hydroxycholesterol from the 16beta hydroxyl steroid, (25R)-cholest-5-ene-3beta,16beta,26-triol (3a), is also reported.     

A new cytotoxic cholesterol sulfate from marine sponge Halichondria rugosa

A new steroid, 24xi,25-dimethyl-3alpha-hydroxyl-cholest-5-ene-2beta-ol sodium sulfate (1), together with a known steroid, 24xi,25-dimethyl-cholest-5-ene-2beta,3alpha-diol disodium sulfate (2), was isolated from the ethanol extract of marine sponge Halichondria rugosa. Their structures were elucidated on the base of spectroscopic analysis. Both compounds showed cytotoxicity to four human cancer cell lines (BEL-7402, HT-29, SPC-A1 and U-251) with IC(50) values between 6.5 and 23.1 microM.     

Study on the chemical constituents of the South China Sea gorgonian Junceella juncea

A new steroidal glycoside--4'-O-acetyl-3-O-[beta-D-arabino-pyranosyl-oxy]-cholest-5-ene-3beta,19-diol (1), and a new glycerol derivative--1,2-O-[2'-hydroxyoctadecyl]-glycerol (2), along with 16 known compounds were isolated from the EtOH/CH2Cl2 extracts of the South China Sea gorgonian coral Junceella juncea. The structures of 1 and 2 were established by extensive spectroscopic analysis, including 1D and 2D NMR data.