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.     

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) .     

Glycosides of marine invertebrates. XIII. New holothurinogenins of holothurin B1 fromHolothuria floridana

We have isolated for the first time the native aglycone of a triterpene glycoside of the holoturin series — holothurin B₁ — and have established its structure as holost-9-ene-3β,12α,17α-triol. The structures of two new holostane derivatives have been established — holosta-8,11-diene-3β,17α-diol and 3β,17α-dihydroxyholost-9-en-12-one. A scheme of transformation of the native genin of holothurin B₁ under the conditions of the acid splitting of the glycoside has been put forward.     

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.     

Studies on Taxol biosynthesis: preparation of taxadiene-diol and triol derivatives by deoxygenation of taxusin

The putative Taxol biosynthesis metabolites, taxa-4(20),11(12)-diene-5α,13α-diol (7), taxa-4(20),11(12)-diene-5α,9α,13α-triol (9), and taxa-4(20),11(12)-diene-5α,10β,13α-triol (10), have been prepared by Barton deoxygenation of the C-9 and C10-hydroxyl groups of protected derivatives of taxusin, a major taxoid metabolite isolated from Yew heart wood. The synthetic protocol devised is amenable for the preparation of isotopically labeled congeners that will be useful to probe further intermediate steps in the biosynthesis of Taxol.     

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.     

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.     

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.     

Microbial hydroxylation of pregnenolone derivatives

Pregnenolone and pregnenolone acetate were incubated with the fungi Cunninghamella elegans, Rhizopus stolonifer and Gibberella fujikuroi. Incubation of with C. elegans yielded metabolites, 3beta,7beta,11alpha-trihydroxypreg-5-en-20-one, 3beta,6alpha,11alpha,12beta,15beta-pentahydroxypreg-4-en-20-one and 3beta,6beta,11alpha-trihydroxypreg-4-en-20-one, while incubation with G. fujikuroi yielded two known metabolites, 3beta,7beta-dihydroxypregn-5-en-20-one and 6beta,15beta-dihydroxypreg-4-ene-3,20-dione. Metabolites and were found to be new. Fermentation of by C. elegans yielded four known oxidative metabolites, androsta-1,4-diene-3,17-dione, 6beta,15beta-dihydroxyandrost-4-ene-3,17-dione and 11alpha,15beta-dihydroxypreg-4-ene-3,20-dione. Fermentation of with R. stolonifer yielded two known metabolites, 11alpha-hydroxypreg-4-ene-3,20-dione and. Compounds were screened for their cholinesterase inhibitory activity in a mechanism-based assay.     

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.     

Terpenoids from Chloranthus multistachys

Two new diterpenoids, ent-17-hydroxyl-16beta-methoxyl-kauran-3-one (1) and ent-17-acetoxyl-16beta-methoxyl-kauran-3-one (2), along with nine known compounds (3-12), ent-17-hydroxyl-kaur-15-en-3-one (3), ent-3beta-acetoxyl-kaur-15-en-16beta, 17-diol (4), ent-kauran-3beta, 16beta, 17-triol (5), ent-3beta-acetoxyl-kauran-16beta, 17-diol (6), ent-kauran-16beta, 17-diol (7), abbeokutone (8), ent-17alpha-acetyl-16beta-hydroxyl- kauran-3-one (9), shizukaol F (10), cycloshizukaol A (11) and curcolonol (12), were isolated from Chloranthus multistachys (Chloranthaceae). Their structures were elucidated by spectroscopic spectra.     

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 ).     

Justiciosides E-G, triterpenoidal glycosides with an unusual skeleton from Justicia betonica

Three new triterpenoidal glucosides, justiciosides E, F and G, were isolated from the aerial portion of Justicia betonica. Their structures were established through chemical and spectroscopic analyses, and showed an unusual A-nor-B-homo oleanan-12-ene skeleton type for the aglycone moiety as A-nor-B-homo-oleanan-10,12-diene-3β,11α,28-triol 28-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside, A-nor-B-homo-oleanan-10,12-diene-3β,11α,28-triol 28-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside, and 11α-methoxy-A-nor-B-homo-oleanan-10,12-diene-3β,11α,28-triol 28-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside, respectively.     

7-Oxodihydrokarounidiol [7-oxo-D:C-friedo-olean-8-ene-3 alpha,29-diol], a novel triterpene from Trichosanthes kirilowii.

The structure of 7-oxodihydrokarounidiol [7-oxo-D:C-friedo-olean-8-ene-3 alpha,29-diol], isolates from the seeds of Trichosanthes kirilowii (Cucurbitaceae), was determined by chemical correlation with karounidiol [D:C-friedo-oleana-7,9(11)-diene-3 alpha,29-diol] from the same source. Two other natural products, viz. bryonolic acid (3 beta-hydroxy-D:C-friedo-olean-8-en-29-oic acid) and bryononic acid (3-oxo-D:C-friedo-olean-8-en-29-oic acid), were also correlated with karounidiol.     

Microbial transformation of dehydroepiandrosterone

Transformation of dehydroepiandrosterone (DHEA) (1) was carried out by a plant pathogen Rhizopus stolonifer, which resulted in the production of seven metabolites. These metabolites were identified as 3beta,17beta-dihydroxyanandrost-5-ene (2), 3beta,17beta-dihydroxyandrost-4ene (3), 17beta-hydroxyandrost-4-ene-3-one (4), 3beta,11-dihydroxyandrost-4-ene-17-one (5), 3beta,7alpha-dihydroandrost-5-ene-17-one (6), 3A,7alpha,17beta-trihydroxyandrost-5-ene (7) and 11beta-hydroxyandrost-4,6-diene-3,17-dione (8). The structures of the transformed products were determined by the spectroscopic techniques.     

Polyhydroxylated steroids and other constituents of the soft coral Nephthea chabroli

Polyhydroxylated steroids and other metabolites were isolated from the soft coral Nephthea chabroli collected in South China Sea. The structures of two new compounds were determined to be 24-methylcholesta-9(11), 24(28)-diene-3beta,12alpha,19-triol and 4alpha-methyl-3beta,14beta-dihydroxy-5alpha-ergost-24(28)-en-23-one on the basis of spectroscopic analysis. Cytotoxic activities of the polyhydroxylated sterols were evaluated on prostate carcinoma LNCaP cell line.     

New glycosides from the Japanese fern Hymenophyllum barbatum

Thirteen glycosides and methyl (3R,5R)-5-hydroxy-(beta-D-glucopyranosyloxy)-hexanoate were newly isolated from the Japanese fern Hymenophyllum barbatum, although our previous work revealed the isolation of hemiterpene glycosides, hymenosides A-J, from the same species. The structures of the newly isolated glycosides were elucidated by extensive two-dimensional (2D) NMR and/or chemical evidence. The structures of those aglycones were divided into four types, 2-methyl-but-2-ene-1,4-diol, 2-hydroxymethyl-but-2-ene-1,4-diol, 2-methylene-butane-1,3,4-triol, and 3-hydroxy-5-hexanolide. The sugar moieties, which were acylated by phenylacetic acid derivatives, were also established by chemical and spectroscopic methods. Eight glucosides of the isolated compounds in the present investigation had a bitter or weakly pungent taste. It is clear that a phenylacetyl group attached to glucose or allose as an ester is necessary for the bitter taste.     

Glycosylation of triterpenoids of the dammarane series. X. Regio- and stereoselective synthesis of 20(S)-protopanaxadiol 3-O-β-D-glucopyranoside (ginsenoside Rh2)

The regio- and stereoselective synthesis of ginsenoside R_h2, which possesses antitumoral activity, has been effected by the glycosylation of 12β-acetoxydammar-24-ene-3β,20(S)-diol. Condensation with α-acetobromoglucose was carried out in the presence of silver oxide in dichloroethane at room temperature, and the yield of the desired glycoside amounted to 50%. A method for the selective protection of the C-12-OH group of dammar-24-ene-3β,12β,20(S)-triol [20(S)-protopanaxadiol] has been proposed. Pacific Ocean Institute of Bioorganic Chemistry, Far Eastern Branch, USSR Academy of Sciences, Vladivostok. Translated from Khimiya Prirodnykh Soedinenii, Vol. 6, pp. 813–816, November–December, 1989.     

Unusual sulfated marine steroids from the ophiuroid ophioderma longicaudum

Polar extracts of the ophiuroid Ophioderma longicaudun contain unusual sterol sulfates together with a mixture of common 3β-hydroxysterol sulfates. The more polar compound has been shown to be 5β-cholestane-3, 4,11β,12β,21-pentol 3,21-disulfate 1. A second group of unusual compounds are disulfated 3,21-dihydroxysteroids. After solvolysis to remove the sulfate groups they have been identified as : (20R)-5-cholestane-3, 21-diol 4a, (20R)-cholest-5-ene-3,21-diol 5a, (20R22E)-cholest-5,22-diene-3,21-diol 6a and (20R)-24-methylcholest-5,24(28)-diene-3,21-diol 7a. Analysis of the “non-sulfated” sterol fractions has shown the presence of common 3β-hydroxy sterols.