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.     

A new cerebroside from fruits of Ailanthus altissima Swingle

A new cerebroside and three known cycloartan triterpenes were isolated from fruits of Ailanthus altissima Swingle. Their structures were identified as 1-O-beta-D-glucopyranosyl-(2S, 3R, 4E, 9E)-2-(2'R-hydroxyhexadecenoy)-4, 9-octadecadiene-1, 3-diol (1), 9, 19-cyclolanost-23 (Z)-ene-3beta, 25-diol (2), cycloart-25-ene-3beta, 24R-diol (3), and cycloart-25-ene-3beta, 24S-diol (4) by means of chemical and spectroscopic analysis. Compounds 2, 3, and 4 were isolated from genus Ailanthus for the first time. The analgesic activity of 1 was also evaluated.     

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.     

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.     

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.     

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%.     

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.     

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.     

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.     

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 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.     

Antiulcer activities of glycyrrhetinic acid derivatives in experimental gastric lesion models

Glycyrrhetinic acid (Ia) and eighteen related derivatives were examined for antiulcer activity using stress-induced gastric lesions (restraint plus water immersion at 25 degrees C) in mice and rats as screening tests. Among the compounds tested, dihemiphthalate derivatives of 18 alpha- or 18 beta-olean-12-ene-3 beta,30-diol (IV, IIId), 18 beta-olean-9(11)12-diene-3 beta,30-diol (VIc), and olean-11,13(18)-diene-3 beta,30-diol (VIIc) showed potent inhibition of gastric lesion formation at a dose of 12 or 25 mg/kg (p.o.); carbenoxolone sodium (Ib) significantly suppressed the lesion formation at a dose of 500 mg/kg (p.o.). Further evaluation of the antiulcer activity was carried out mainly for compound IIId. Compound IIId (p.o.) prevented the formation of indomethacin-induced or 0.6 N HCl-induced gastric lesions; the latter antiulcer effect was noted even in the combined treatment with indomethacin, suggesting that the effect occurs independently of endogenous prostaglandins. In contrast, compound IIId had no preventive effect against Shay rat ulcer when intragastrically (i.g.) administered; further, no antisecretory effect was seen by i.g. application in pylorus-ligated rats. Administration of compound IIId for 2 weeks accelerated the healing rate of acetic acid-induced gastric ulcer in rats. No significant change in urine excretion was observed after its consecutive administration for 3 d. These results suggest that dihemiphthalate derivatives (IIId, IV, VIc, VIIc) may produce a strong antiulcer activity, probably by strengthening some gastric mucosal defensive mechanism.     

Triterpenoids from the stembark of Pyrus communis

Three triterpenoids were isolated from the stem bark of Pyrus communis Linn. and identified as lup-20(29)-ene-3alpha, 27-diol (1), lup-20(29)-ene-3alpha-ol (2) and lup-20(29)-ene-3alpha, 28-diol (3) on the basis of spectral and chemical analysis. The Compound (1) is a novel triterpene, being reported first time by us.     

Steroids of the spirostan and furostan series from Nolina microcarpa I. Structures of nolinospiroside C and nolinofurosides A and C

In addition to the know steroid sapogenin (25S)-ruscogenin (I), three new glycosides have been isolated from the leaves ofNolina microcarpa S. Wats. (family Dracaenacea), and the following structures are suggested for them: (25S)-spirost-5-ene-1β,3β-diol 1-O-β-D-fucopyranoside (nolinospiroside C, II), (25S)-furost-5-ene-1β,3β,22α,26-tetraol 1-O-β-D-fucopyranoside (nolinofuroside A, III), and (25S)-furost-5-ene-1β, 3β, 22α, 26-tetraol 1-O-β-D-fucopyranoside 26-O-β-D-glucopyranoside (nolinofuroside C, V).     

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.     

An acetoxygenated analogue of ergosterol from a soft coral of the genus Lobophytum

Chemical investigation of a soft coral of the genus Lobophytum of the Andaman and Nicobar coasts resulted in the isolation of a new marine sterol acetate, (24S)-ergostane-3beta,5alpha,6beta,25-tetraol-3,6,25-triacetate (1) and of two known sterol glycosides 3beta,4alpha-dihydroxypregn-20-ene-4-O-beta-D-arabinopyranoside and 24-methylenecholest-5-ene-3beta,7beta, 16beta-triol-3-O-alpha-L-fucopyranoside-7beta-acetate. The structures of the compounds were elucidated based on spectral studies and chemical conversions.     

Dammarane triterpenes of Commiphora confusa resin

Fractionation of a steam distilled residue of Commiphora confusa resin has yielded four novel dammarane triterpenes characterised as (20S)-3beta-acetoxy-12beta,16beta-trihydroxydammar-24-ene, (20S)-12beta,16beta-trihydroxydammar-24-ene-3beta-O-beta-glucopyranoside, (20S)-3beta-acetoxy-12beta,16beta,25-tetrahydroxydammar-23-ene, and (20S)-3beta,12beta,16beta,25-pentahydroxydammar-23-ene. The known compounds beta-amyrin, 3beta-amyrinacetate, 2-methoxyfuranodienone, 2-acetoxyfuranodienone, (20R)-3beta-acetoxy-16beta-dihydroxydammar-24-ene, (20R)-3beta,16beta-trihydroxydammar-24-ene, 3beta-acetoxy-16beta-hydroxydammar-24-ene, 3beta-hydroxydammar-24-ene, 3beta-acetoxydammar-24-ene, and beta-sistosterol were also isolated from the same extract. The structures of the compounds were determined using spectroscopic, physical, and chemical methods.     

Synthesis and in vitro antioxidant activity of glycyrrhetinic acid derivatives tested with the cytochrome P450/NADPH system

Five glycyrrhetinic acid (Ib) derivatives have been synthesized to try to improve the antioxidant activity. Their in vitro antioxidant activities were studied using a cytochrome P450/NADPH reductase system from rat liver microsomes. The generation of microsomal free radicals was followed by oxidation of the DCFH-DA probe, while evaluating the capacity to inhibit reactive oxygen species (ROS) formation. Two hydroxylated derivatives, 18beta-olean-12-ene-3beta,11alpha,30-triol (II) and 18beta-olean-12-ene-3beta,11beta,30-triol (IV), exhibited strong antioxidant activities. At a concentration of 1.0 mg/ml, these derivatives inhibited ROS formation by 50% and 51%, respectively. Moreover, two homo- and heterocyclic diene derivatives, 18beta-olean-11,13(18)-diene-3beta,30-diol (III) and 18beta-olean-9(11),12-diene-3beta,30-diol (V), were also effective in ROS-scavenging activity (inhibition of 41% and 44% of ROS activity, respectively). In the same conditions, the lead compound (Ib) and the reference vitamin E inhibited ROS activity by 31% and 32%, respectively. Our results suggest that the chemical reduction of the 11-keto and 30-carboxyl groups into hydroxyl function (example, II, IV) can increase the antioxidant activity of Ib significantly. In view of these results, our study represents a further approach to the development of potential therapeutic agents from Ib derivatives for use in pathologic events in which, free radical damage could be involved.     

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)].     

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.