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 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.     

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.     

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.     

Novel lanostane and rearranged lanostane-type triterpenoids from Abies sachalinensis - II -

In the previous work we reported five A-seco-rearranged lanostane triterpenoids as antibacterial constituents from the ethyl acetate soluble fraction of Abies sachalinensei leaves. In further study on the isolation of constituents from the ethyl acetate soluble fraction, two new rearranged lanostane and lanostane-type triterpenoids (3, 4) and three reported compound (1, 2, 5) were isolated. The structures of new compound 3 and 4 were determined to be 3,4-seco-4(28),6,8(14),24-mariesatetraen-26,23-olide-23-hydroxy-3-oic acid and 3,4-seco-4(28),7,24-lanostatrien-26,23-olide-23-hydroxy-3-oic acid, respectively, by spectral studies on HR-MS, (1)H-NMR, (13)C-NMR, and 2D-NMR spectra. Compound 1 was identified with pindrolactone and its structure was revised as 7,14,22Z,24-mariesatetraen-26,23-olide-3alpha-ol. Structures of 2 and 5 were determined as 7,14,24-mariesatrien-26,23-olide-3alpha,23-diol and 3alpha-hydroxy-7,14,24E-mariesatrien-23-oxo-26-oic acid. Of these compounds, 2, 3 and 4 were obtained as lactol tautomer mixtures at gamma-lactone structures of side chains.     

Practical Syntheses of Some Insect Sex Pheromones, 10- and 12-Alken-1-ol Acetates

Some insect sex pheromones 10-dodecen-1-ol acetates 5a(Z/E) and 12-tetradecen-1-ol acetates 5b(Z/E) have been synthesized from cis-13-docosenoic acid la and cis-15-tetracosenoic acid Ib via the isomerization of key intermediates 11-dodecen-1-ol acetate 4a and 13-tetradodecen-1-ol acetate 4b.     

New Olefinic Cyclizations by Oxymetallation. Conversion of (−)-elemol to (−)-selina-4α, 11-diol (cryptomeridiol) and (−)-guai-1 (10)-ene-4α, 11-diol

Acetoxythallation of (?)-elemol acetate ( 1b ) yields a diacetate 2b which after treatment with lithium aluminium hydride gives (?)-guai-1 (10)-ene-4α, 11-diol ( 2a ). (?)-Elemol ( 1a ) is converted to (?)-selina-4α, 11-diol ( 9 , cryptomeridiol) by hydroxymercuration followed by reductive demercuration. (+)-γg-Elemene ( 5 ) similarly yields (+)-selin-7(11)-en-4α-ol ( 11 , juniper camphor). The stereochemistry and mechanism of these metal salt-induced olefinic cyclization and their biogenetic implication are discussed.     

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%.     

Photosensitized Oxygenation of Abieta-7,9(11)-dien-13β-ol

Dehydration of abiet-8-ene-7β, 13β-diol (ibozol, 1 ) leads to abieta-7,9(11)-dien-13β-ol ( 2 ) which aromatizes slowly to the known abieta-8,11,13-triene ( 3 ). Photosensitized oxygenation of the heteroannular diene 2 yields a mixture from which three compounds were identified; abiet-7-ene-9α, 11α, 13β-triol ( 4 ), abieta-8,11,13-trien-7-one ( 5 ), and abieta-8,11,13-trien-7α-ol ( 6 ).     

Monoterpene glycosides from Indigofera hetrantha

Monoterpene glycosides have been isolated from the ethyl acetate soluble fraction of Indigofera hetrantha and their structures assigned to be 3,7-dimethyl-2(E),6-octadien-5-one-1-O-beta-D-6-O-acetylglucopyranoside (1) and 3,7-dimethyl-2(E), 6-octadien-5-one-1-O-[-beta-D-6'-O-acetylglucopyra-nosyl (1' --> 6')-beta-D-glucopyranoside] (2), on the basis of spectroscopic analysis including 1D and 2D NMR techniques. Compounds 1 and 2 displayed moderate inhibitory potential against the enzyme lipoxygenase.     

Two new guaianolides from Amberboa ramosa

Two new sesquiterpene lactones named amberbins A (1) and B (2), have been isolated from the ethyl acetate soluble fraction of Amberboa ramosa, together with jaseocidine (3), crysoeriol (4) and 3beta,8alpha-dihydroxy-11alpha-methyl-1alphaH,5alphaH,6betaH, 7alphaH,11betaH-guai-10(14), 4(15)-dien-6,12-olide (5). The structures of the isolated compounds have been elucidated on the basis of their spectroscopic data.     

Chemical constituents of Melicope ptelefolia

Phytochemical investigations on the methanolic extract of Melicope ptelefolia Champ ex Benth. resulted in the isolation of three new compounds, identified as 3beta-stigmast-5-en-3-ol butyl tridecanedioate (melicoester) (1), (2Z, 6Z, 10Z, 14Z, 18Z, 22Z, 26E)-3', 7', 11', 15', 19', 23', 27', 31'-octamethyldotriaconta-2, 6, 10, 14, 18, 22, 26, 30-octadecanoate (melicopeprenoate) (2) and p-O-geranyl-7"-acetoxy coumaric acid (3). The compounds were isolated along with twenty-one other known compounds, lupeol (4), oleanolic acid (5), kokusaginine (6) genistein (7), p-O-geranyl coumaric acid (8), 4-stigmasten-3-one (9), 3beta-hydroxystigma-5-en-7-one (10) cis-phytyl palmitate (11), dodecane, dodecan-1-ol, ceryl alcohol, hentriacontanoic acid, eicosane, n-amyl alcohol, caprylic alcohol, octatriacontane, nonatriacontane, hexatriencontan-1-ol, methyl octacosanoate, beta-sitosterol, beta-sitosterol glucoside. Structures of all the compounds were established on the basis of MS and 1D and 2D NMR spectral data, as well as comparison with reported data.     

Three New Cycloartenol Triterpenoid Saponins from the Roots of Cimicifuga simplex Wormsk

Three new cycloartenol triterpene saponins, named shengmaxinsides A-C, have been isolated from the ethyl acetate soluble fraction of an ethanol extract of Cimicifuga simplex Wormsk roots. Their structures were established by chemical tests and detailed spectroscopic analysis as 25-O-acetyl-7,8-didehydrocimigenol-3-O-β-D-galactopyranoside (1), 7,8-didehydrocimigenol-3-O-β-D-galactopyranoside (2) and 7,8-didehydro-24S-O-acetylhydroshengmanol-3-O-β-D-galactopyranoside (3), respectively.     

New Dolabellane Derivatives from the Brown Alga Dictyota pardalis

Reinvestigation of the brown alga Dictyota pardalis f. pseudohamata CRIBB led to the crystallization of 1 and to the isolation of the two new dolabellane derivatives 2 and 3 . X-Ray analysis of 1 and 2 , together with detailed 1D-and 2D-NMR studies on 2 and 3 , allowed their structures to be elucidated as (1R*,3S*,7S*,11R*,4Z)-dolabella-4,8(17), 12(18)-triene-3,7-diol ( 1 ), (1R*,3S*,4S*,7S*,8S*,11R*,14R*,12E)-3,4:7,8-diepoxydolabe11-12-ene-14, 18-diol ( 2 ), and (1R*,3S*,4S*,7S*,8S*,11R*,14R*)-3,4:7,8-diepoxy-l,4,8,12,12-pentamethylbicyclo[9. 3. 0]tetra-decan-14-ol( 3 ).     

A study of the properties and13C NMR spectra of pinifolic acid and its derivatives

The properties and¹³C NMR spectra of pinifolic acid (13S-labd-8,17-ene-15,18-dioic acid), its monomethyl ester, its dimethyl ester, its dicyclohexylammonium salt, dihydropinifolic acid, 18-hydroxy-13S-labd-8(17)-en-15-oic acid, the cyclohexylammonium salt of the monomethyl ester, the bis(diethylammonium) salt, pinifodiol (13S-labd-8(17)-ene-15,18-diol), the acetate of 18-hydroxy-13S-labd-8(17)-en-15-oic acid, and the diacetate of pinifodiol have been studied.     

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.     

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).     

Xanthine oxidase inhibiting flavonol glycoside from Amberboa ramosa

A new flavonol glycoside (1) has been isolated from the ethyl acetate soluble fraction of Amberboa ramosa and assigned the structure 5,7,4'-trihydroxy-3,8-dimethoxylflavone 5-O-beta-D-gluco-pyranoside (1). In addition, 6,4'-dihydroxy-3,5,7-trimethoxyflavone (2), 5,7-dihydroxy-4'-methoxyflavone (3) and (23R)-5alpha-cycloart-24-ene-3beta,21,23-triol (4) have also been reported for the first time from this species. The structures were deduced on the basis of 1D and 2D NMR techniques. The compounds 1-3 displayed weak to moderate inhibition against the xanthine oxidase enzyme.     

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.