Further studies on the sesquiterpene ketone germazone

Germazane type sesquiterpenoids germazol (2), 7(11)-dihydrogermazol (3), 7(11)-dihydrogermazone (4), germazene-7(11) (17) and germazane (18) have been prepared from germazone (1). The presence and location of the cyclobutane ring in germazone (1) was confirmed by the acid-catalyzed cleavage of 2 to the cis-eudesmane derivatives 6,7 and 8.     

Four new eremophilendiolides from Ligularia atroviolacea

From Ligularia atroviolacea, four new eremophilendiolides, 81$-hydroxy-eremophil-3,7 （11）-dien-12,8α（14,6α）-diolide （1）, 8β-methoxy-eremophil-3,7（11）-dien-12,8α（14,6α）-diolide （2）, 8α-hydroxy-eremophil-3,7（11）-dien-12,8lβ（14,6α）-diolide （3） and eremophil-3,7（11）,8-trien-12,8 （14,6α）-diolide （4）, as well as a known diolide （5） were isolated. Their structures were elucidated on the basis of 1D and 2D NMR as well as ESI-MS spectral data.     

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.     

Extrusion reactions-VII

ω-(2,6-Dimethyl-4-pyrimidinylthio-(4), 2-methyl-4-quinazolinylthio-(9), and 4-oxo-2-quinazo-linylthio)-(10) acetophenones with hydrochloric or perchloric acid provide 2,5-diaryl-1,4-dithiins (7) whereas α)-(6-methyl-4-pyrimidinylthio) acetophenones (11) with aq HCl/HClO₄, or POCl₃ followed by hydrolysis provide 1-(4-aryl-2-thiazolyl)-2-propanones (12). Likewise, 2-(6-methyl-4-pyrimidinylthio) cyclohexanone (13) give the thiazole derivative (14).     

Siliciumorganische verbindungen: LXXXVIII. Disilatranylalkane

By hydrosilylation of triethoxyvinylsilane (1), 1,5-hexadiene (10) and 3,3-dimethyl-3-sila-1,4-pentadiene (14) with triethoxysilane (2) we obtained 1,2-bis(triethoxysilyl)ethane (3), 1,6-bis(triethoxysilyl)hexane (11) and 1,5-bis(triethoxysilyl)- 3,3-dimethyl-3-silapentane (15). The reaction of 3 with triethanolamine (4), triisopropanolamine (6) and tris(1-t-butyl-ethanol)amine (8) leads to the 1,2-disilatranylethanes 5, 7 and 9. The 1,6-disilatranylhexanes 12 and 13 are formed from 11, 4 and 6 respectively, and 15 with 4 gives 3,3-dimethyl-1,5-disilatranyl-3-silapentane (16).     

Sesterterpenes and phenolic alkenes from the Thai sponge Hyrtios erectus

Sesterterpene, erectusolide A (1), six phenolic alkenes, erectuseneols A?F (2–7) and nine known compounds, luffalactone (8), luffariolide E (9), (6E)- and (6Z)-neomanoalide 24,25-diacetates (10 and 11), 6,6-dimethylundecane-2,5,10-trione (12), threo- and erythro-cavernosines (13 and 14), (4E,6E)-dehydromanoalide (15), echinoclerodane A (16), were isolated from the marine sponge Hyrtios erectus. Compound 13 was isolated for the first time from a natural source. The structures of these compounds were elucidated on the basis of spectroscopic analysis. The phenolic alkenes 3 and 7, the sesterterpenes 8–11 and 15, and compounds 12–14 were evaluated for cytotoxic activities against six cancer cell lines, MOLT-3, HepG2, HeLa, HuCCA-1, A549, and MDA-MB-231.     

Highly oxidized ergosterols and isariotin analogs from an entomopathogenic fungus,Gibellula formosana,cultivated in the presence of epigenetic modifying agents

The concomitant addition of a histone deacetylase inhibitor, suberoyl bis-hydroxamic acid, and a DNA methyltransferase inhibitor, RG-108, to the culture medium of Gibellula formosana, an entomopathogenic fungus, induced a significant increase in diversity of secondary metabolites. From the culture media were isolated two new highly oxidized ergosterols, formosterols A (1) and B (2), and five new isariotin analogs, 12′-O-acetylisariotin A (4), 1-epi-isariotin A (5), and isariotins K–M (6–8), together with 22,23-epoxy-3,12,14,16-tetrahydroxyergosta-5,7-dien-11-one (named formosterol C) (3), isariotins A (9), C (10), and E (11), TK-57-164A (12), and beauvericin (13). The NMR spectra, X-ray single crystallographic diffraction, and chemical transformations revealed the structures of the two new formosterols and five new isariotins. The stereochemistry of formosterol C (3) was deduced from its spectroscopic data. The side chains of formosterols A–C (1–3) contained cis-22,23-epoxide, which is rarely present in naturally occurring sterols and triterpenes.     

Pseudoazulene. reaktionen von fulvenen mit 3,6-dicarbomethoxy-1,2,4,5-tetrazin

Fulvenes (1) react with 3,6-dicarbomethoxy-1,2,4,5-tetrazine (2) to give 4a,5-dihydro-2H-cyclopenta[d]pyridazines (3), which can be transformed with mangandioxide to the dehydrocompounds 4. Through 1,6-addition of hydrogen pseudoazaazulenes of the 2H-cyclopenta[d]pyridazin type (6) are obtained. Oxidative C-C-connection of these compounds yields dehydrodimers (10), which on hydrogenation give bis-pseudoazaazulenes (11).     

Oxidation of 3-hydroxyflavones in the presence of copper(I) and copper(II) chlorides

The reactions of 3-hydroxyflavones with dioxygen in the presence of CuCl and CuCl₂ have been studied. 2-Benzoyl-2-hydroxy-3(2H)-benzofuranone (2) was formed along with 2-hydroxybenzil (4), salicylic acid (5), benzoic acid (6), coumaronedione (8) and the depside (11). A copper(II) flavonolate complex has been also isolated.     

Rules for ring closure: application to intramolecular aldol condensations in polyketonic substrates

An extension of the nomenclature for classifying ring closures to include intramolecular reactions of enolate anions is described, and the rules governing such cyclizations are enumerated. The syntheses of the polyketonic substrates 4-acetyl-2,6-heptanedione (11), 4-acetyl-4-methyl-2,7-octanedione (24), and 3-acetyl-3-methyl-1,6-diphenyl-1,6-heptanedione (33) were carried out, and their base-induced intramolecular aldol condensations studied. With each substrate a favored 6-(enolendo)-exo-trig cyclization to produce cyclohexenone products was the only ring forming reaction observed, this process predominating in all instances over competing disfavored 5-(enolendo)-exo-trig closures, and also over other competing favored cyclizations. The identity of the cyclization product 12 derived from 11 was confirmed by aromatizing 12 to 17, and alternately synthesizing 17 from 3-bromo-5-methylphenol.     

Aigialomycins and related polyketide metabolites from the mangrove fungus Aigialus parvus BCC 5311

Reinvestigation of the secondary metabolites from the marine mangrove fungus Aigialus parvus BCC 5311 led to the isolation of six new nonaketide metabolites, aigialomycins F (4) and G (5a/5b), 7′,8′-dihydroaigialospirol (7), 4′-deoxy-7′,8′-dihydroaigialospirol (8), and rearranged macrolides 9 and 10, along with six previously described compounds, hypothemycin (1), aigialomycins A (2) and B (3), aigialospirol (6), 4-O-demethylhypothemycin (11), and aigialone (12). The structures of the new compounds were elucidated by analyses of the NMR spectroscopic and mass spectrometry data in combination with chemical means.     

New potent cytotoxic lamellarin alkaloids from Indian ascidian Didemnum obscurum

Chemical investigations of the ascidian Didemnum obscurum has resulted in the isolation of four new lamellarin alkaloids, lamellarin-ζ (1), lamellarin-η (2), lamellarin-? (3) and lamellarin-χ (4) along with seven known lamellarins, lamellarin-K (5), lamellarin-I (6), lamellarin-J (7), lamellarin-K triacetate (8), lamellarin-L triacetate (9), lamellarin-F (10) and lamellarin-T diacetate (11). The structures of the compounds 1-11 were established by detailed analysis of NMR spectral data. Cytotoxic activity of the isolates has been done against coloractal cancer cells.     

Quinolizidines—IV: Total syntheses of (±)-ankorine and (±)-11-methoxyprotoemetinol

The first total synthesis of ankorine (4), an Alangium lamarckii alkaloid, has been accomplished in the form of a recemic modification by means of an initial condensation of 2-benzyloxy-3,4-dimethoxyphenacyl bromide with the lactim ether 6, derived from ethyl (±)-trans-5-ethyl-2-oxo-4-piperidineacetate (5), and succeeding steps proceeding through the intemediates 7a, 8a, 9a, 10a (X=Cl), 11a, and 12a. A parallel synthetic route starting with 3,4,5-trimethoxyphenacyl bromide and 6 gave (±)-11-methoxyprotoemetinol (12c) via the intermediates 7c, 8c, 9c, 10c (X =I,ClO₄), and 11c. The trimethyl ether 12c did not match the O-Me derivative (type 12e) of natural ankorine. Thus, the formula 4 defines the structure and relative stereochemistry of ankorine.     

Cyclooxygenase-2 enzyme inhibitory withanolides from Withania somnifera leaves

Four novel withanolide glycosides and a withanolide have been isolated from the leaves of Withania somnifera. The structures of the novel compounds were elucidated as physagulin D (1→6)-β-d-glucopyranosyl-(1→4)-β-d-glucopyranoside (1), 27-O-β-d-glucopyranosyl physagulin D (2), 27-O-β-d-glucopyranosyl viscosalactone B (3), 4,16-dihydroxy-5β, 6β-epoxyphysagulin D (4), and 4-(1-hydroxy-2,2-dimethylcyclo-propanone)-2,3-dihydrowithaferin A (5) on the basis of 1D-, 2D NMR and MS spectral data. In addition, seven known withanolides withaferin A (6), 2,3-dihydrowithaferin A (7), viscosalactone B (8), 27-desoxy-24,25-dihydrowithaferin A (9), sitoindoside IX (10), physagulin D (11), and withanoside IV (12) were isolated. These withanolides were assayed to determine their ability to inhibit cycloxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes and lipid peroxidation. The withanolides tested, except compound 9, showed selective COX-2 enzyme inhibition ranging from 9 to 40% at 100 μg/ml. Compounds 4, 10 and 11 also inhibited lipid peroxidation by 40, 44 and 55%, respectively. The inhibition of COX-2 enzyme by withanolides is reported here for the first time.     

Potential anti-inflammatory diterpenes from Premna obtusifolia

Eleven new diterpenoids: pimaranes (1,2), rosanes (3) abietanes (4–7), icetexanes (8), and rearranged icetexanes (9–11), together with fifteen known diterpenes (12–26) and two known sesquiterpenes (27,28) have been isolated from the roots and twigs of Premna obtusifolia. The structures of these compounds were elucidated on the basis of spectroscopic analysis and X-ray crystallographic data of 8 and 9 were also determined. The antibacterial and anti-inflammatory activities of the isolates were evaluated.     

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.     

A new synthesis of theaspirone,an odiferous principle of tea

A new synthesis of theaspirone (10) is recorded. The key step involves coupling between the organolithium reagent 6, derived from 4-bromo-2-butanol (4), and the monoketal of 4-ketoisophorone (3). Removal of protecting groups and ether cyclization then gave theaspirone 10 and its diastereoisomer 11.     

Limonoids of calamondin seeds

Five new limonoids were isolated from calamondin seeds: methyl deacetylnomilinate (7), calamin (9), retrocalamin (10), cyclocalamin (11), and methyl isoobacunoate diosphenol (13). Structures were assigned on the basis of ¹H and ¹³CNMR spectra, and chemical conversions of 9 to 10, 11, and 13. These reactions are also biogenetically plausible. Both 11 and the structurally similar limonoid rutaevin have been assigned the 5β-H configuration, which is opposite to that of all other known Rutaceae limonoids. ¹³CNMR data are presented for 15 limonoids.     

Prostaglandin chemistry—VIII : Synthesis of optically active 7-oxoprostaglandins

Regiospecific α-acylation of β-alkenylated enolates generated by conjugate addition of lithium organocuprates to α,β-unsaturated ketones is described. Several new 7-oxoprostaglandin analogues, 7-oxoprostaglandin E₁ (18), 11-deoxy-7-oxoprostaglandin E₁ (23), and their 15-epi enantiomers 17 and 22, were synthesized by conjugate addition-acylation method. From optically active 4(R) -t - butyldimethylsiloxycyclopent - 2 - en - 1 - one (R-11), 7-oxoprostaglandin E₁ (18) was synthesized. Determination of the absolute configuration of 11-deoxy-7-oxoprostaglandin E₁ (23) and its 15-epi enantiomer (22) on the basis of CD study is described. Successful acylation of β-alkenylated lithium copper enolates with reactive acylating agents such as thiol esters and N-acyl imidazole as well as acyl halides is described.     

Chlorinated chromone and diphenyl ether derivatives from the mangrove-derived fungus Pestalotiopsis sp. PSU-MA69

Four new diphenyl ethers, pestalotethers A–D (1–4), three new chromones, pestalochromones A–C (5–7), one new xanthone, pestaloxanthone (8), and one new butenolide, pestalolide (9), together with 11 known compounds were isolated from the mangrove-derived fungus Pestalotiopsis sp. PSU-MA69. Their structures were established by spectroscopic techniques. Compounds 1–3 and 5–7 are the rare chlorinated fungal metabolites of diphenyl ethers and chromones, respectively. Pestalolide (9) displayed weak antifungal activity against Candida albicans and Cryptococcus neoformans.