Prenylated Phloroglucinol Derivatives from Hypericum perforatum var. angustifolium

Two new prenylated phloroglucinol derivatives and 15 known compounds were isolated from the aerial parts of Hypericum perforatum var. angustifolium. Their structures were determined on the basis of spectroscopic evidence.     

Pyrohyperforin, A New Prenylated Phloroglucinol from Hypericum perforatum

The antidepressant activity of Hypericum perforatum extracts has sparked great interestin the chemistry and biochemistry of its constitUents, generating coverage also on themainstream press'. The major limitation to a rational exploitation of the medicinalpotential of this plant is our still incomplete knowledge of its active constitUents. In the1970s, Rusian workers described the isolation and characterization of one activeconstitUent named hyperforin (l) from Hypericum perforatum'". Then …     

Polyprenylated Phloroglucinol Derivatives from Hypericum sampsonii

Six new prenylated phloroglucinol derivatives, hypersampsones A–F ( 1 – 6 ), were isolated from the aerial part of Hypericum sampsonii, together with 2,4,6‐trihydroxybenzophenone, 2,4,6‐trihydroxybenzophenone 4‐O‐geranyl ether, 2,4,6‐trihydroxybenzophenone 3‐C‐geranyl ether, sampsoniones D and H. Their structures were elucidated by spectroscopic methods, mainly 1D‐ and 2D‐NMR spectroscopy and mass spectrometry.     

New Phloroglucinol Glycosides from Hypericum japonicum

HyPericumjaPonicumisaChineseherbmedicineusedforthetreatmentofseveralbacterialdiseases,infectioushepatitis,gastrointestinaldisordersandtumors.Inapreviouspaper',wereportedontheseveralconstituentSfromHyPericumjaPonicum.Inacontinuationofthatwork,werecentlyisolatedtwonewphloroglucinolglycosidesfromthisplant.Thispaperdescribesthedeterminationofthosecompounds.ComPound1wasisolatedaspaleyellowcrystals.ThelHNMR(5ooMHz,DMSO-de)andl3CNMR(l25MHz,DMSO-d6)spectraof1revealedaprotonsignalat54.53(d,…     

Ynamide Carbopalladation: A Flexible Route to Mono‐, Bi‐ and Tricyclic Azacycles

Bromoenynamides represent precursors to a diversity of azacycles by a cascade sequence of carbopalladation followed by cross‐coupling/electrocyclization, or reduction processes. Full details of our investigations into intramolecular ynamide carbopalladation are disclosed, which include the first examples of carbopalladation/cross‐coupling reactions using potassium organotrifluoroborate salts; and an understanding of factors influencing the success of these processes, including ring size, and the nature of the coupling partner. Additional mechanistic observations are reported, such as the isolation of triene intermediates for electrocyclization. A variety of hetero‐Diels–Alder reactions using the product heterocycles are also described, which provide insight into Diels–Alder regioselectivity.     

Prenylated Indole Alkaloid Derivatives from Marine Sediment‐Derived Fungus Penicillium paneum SD‐44

Three new prenylated indole alkaloids, including two β‐carbolines, penipalines A and B ( 1 and 2 , resp.), and one indole carbaldehyde derivative, penipaline C ( 3 ), as well as two known indole derived analogs, 4 and 5 , were isolated from the deep‐sea‐sediment derived fungus Penicillium paneum SD‐44 cultured in a 500‐l bioreactor. The structures of the new compounds were determined on the basis of 1D‐ and 2D‐NMR spectroscopy, as well as by high‐resolution mass spectrometry. The new compounds 2 and 3 showed potent cytotoxic activities against A‐549 and HCT‐116 cell lines.     

Construction of Bi‐ and Tricyclic Skeletons by Domino‐Heck–Diels–Alder Reactions

Palladium‐catalyzed intramolecular reactions of 2‐bromo 1,6‐dienes followed by intermolecular [4+2] cycloaddition with suitable dienophiles in one‐pot operations gave hexahydroindenes 8 and 9 in yields of 40–78%, an hexahydro‐s‐indacene derivative 13 could be obtained in up to 25% yield with cyclopent‐2‐en‐1‐one ( 10 ) as a dienophile in the presence of different Lewis acids, and a spirocyclopentane‐hexahydroindenone 18 could be isolated in 72% yield. When in‐situ‐formed iminium salts were used as heterodienophiles, hexahydro‐1H‐[2]pyrindinols 31 could be obtained in a one‐pot two‐step operation in 29–46% yield.     

Highly Efficient Access to Bi‐ and Tricyclic Ketals through Gold‐Catalyzed Tandem Reactions of 4‐Acyl‐1,6‐diynes

Single step : Fused bicyclic and bridged tricyclic ketals were synthesized in a single step from the reactions of easily available 4‐acyl‐1,6‐diynes with H₂O and alkanols (see scheme). The highly efficient AuCl₃‐catalyzed multicomponent domino reactions, involving five C ? O bond formations, can proceed in a highly regio‐ and diastereoselective manner at room temperature under air and lead to structures of high molecular complexity from simple starting materials in an atom economic way.

     

Phloroglucinol Derivatives from Dryopteris crassirhizoma as Potent Xanthine Oxidase Inhibitors

Dryopteris crassirhizoma rhizomes are used as a traditional medicine in Asia. The EtOAc extract of these roots has shown potent xanthine oxidase (XO) inhibitory activity. However, the main phloroglucinols in D. crassirhizoma rhizomes have not been analyzed. Thus, we investigated the major constituents responsible for this effect. Bioassay-guided purification isolated four compounds: flavaspidic acid AP (1), flavaspidic acid AB (2), flavaspidic acid PB (3), and flavaspidic acid BB (4). Among these, 1 showed the most potent inhibitory activity with a half-maximal inhibitory concentration (IC₅₀) value of 6.3 µM, similar to that of allopurinol (IC₅₀ = 5.7 µM) and better than that of oxypurinol (IC₅₀ = 43.1 µM), which are XO inhibitors. A comparative activity screen indicated that the acetyl group at C3 and C3′ is crucial for XO inhibition. For example, 1 showed nearly 4-fold higher efficacy than 4 (IC₅₀ = 20.9 µM). Representative inhibitors (1–4) in the rhizomes of D. crassirhizoma showed reversible and noncompetitive inhibition toward XO. Furthermore, the potent inhibitors were shown to be present in high quantities in the rhizomes by a UPLC-QTOF-MS analysis. Therefore, the rhizomes of D. crassirhizoma could be used to develop nutraceuticals and medicines for the treatment of gout.     

Investigation of ionic liquids under Bi‐ion and Bi‐cluster ions bombardment by ToF‐SIMS

A systematic study of five different imidazolium‐based room temperature ionic liquids, 1‐butyl‐3‐methylimidazolium acetate, 1‐butyl‐3‐methylimidazolium nitrate, 1‐butyl‐3‐methylimidazolium iodide, 1‐butyl‐3‐methylimidazolium hexafluorophosphate and 1‐butyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide were carried out by means of time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) in positive and negative ion mode. The compounds were measured under Bi‐ion and Bi‐cluster ions (Bi_2–7⁺, Bi_{3, 5}²⁺) bombardment, and spectral information and general rules for the fragmentation pattern are presented. Evidence for hydrogen bonding, due to high molecular secondary cluster ions, could be found. Hydrogen bonding strength could be estimated by ToF‐SIMS via correlation of the anionic yield enhancement with solvent parameters. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis,Characterisation and Crystal Structures of Two Bi‐oxadiazole Derivatives Featuring the Trifluoromethyl Group

The synthesis, characterisation, and crystal structure determination of the closely related compounds 3,3′‐bi‐(5‐trifluoromethyl‐1,2,4‐oxadiazole) and 5,5′‐bi‐(2‐ trifluoromethyl‐1,3,4‐oxadiazole) are reported. These two compounds are known for their bioactivity; however, in this study they serve as model compounds to evaluate the suitability of the heterocyclic oxadiazole ring system for energetic materials when the fluorine atoms in the exocyclic CF₃ groups are substituted successively by nitro groups. Quantum chemical calculations for the bi‐1,3,4‐ oxadiazole derivatives with difluoronitromethyl, fluorodinitromethyl, and trinitromethyl groups have been carried out and predict promising energetic performances for both explosive and propulsive applications.     

Bi‐ and Polynuclear Transition‐Metal Carbon Tellurides

The first examples of bi‐ and polynuclear tellurocarbonyl complexes were obtained from the reactions of [W(≡CTe)(CO)₂(Tp*)]NEt₄ (Tp*=hydrotris(dimethylpyrazolyl)borate) with [MCl(PCy₃)]/TlPF₆ (M=Cu, Au) or [Au₂Cl₂(μ‐dppm)], which afford [WM(μ‐CTe)(PCy₃)(CO)₂(Tp*)] (M=Cu, Au) and [WAu₂(μ‐CTe)(μ‐dppm)(CO)₂(Tp*)]₃(PF₆)₃. In all cases it is specifically the tellurocarbonyl that assumes a bridging, but in each case distinct, role including examples of isotellurocarbonyl, semi‐bridging and σ–π coordination and combinations thereof. Tetrametallic complexes bridged by C₂Te and C₂Te₂ ligands are also described.     

New Pyrazolyl‐Nicotinic Acids,Methyl Esters,and 1,3,4‐Oxadiazolyl‐pyrazolyl‐pyridine Tricyclic Scaffold Derivatives from 6‐Hydrazinylnicotinic Acid Hydrazide Hydrate

This paper describes an efficient approach for the synthesis of a new series of 6‐[3‐alkyl(aryl/heteroaryl)‐5‐trifluoromethyl‐1H‐pyrazol‐1‐yl]nicotinic acids (where alkyl = CH₃; aryl = Ph, 4‐OCH₃Ph, 4,4′‐BiPh; and heteroaryl = 2‐Furyl) from the hydrolysis reaction of alkyl(aryl/heteroaryl)substituted 2‐(5‐trifluoromethyl‐5‐hydroxy‐4,5‐dihydro‐1H‐pyrazol‐1‐yl)‐5‐(5‐trifluoromethyl‐5‐hydroxy‐4,5‐dihydro‐1H‐1‐carbonylpyrazol‐1‐yl)pyridines, under basic conditions and at 70–95% yields. In a subsequent step, the esterification reaction of pyrazolyl‐nicotinic acids done in thionyl chloride and methanol led to the isolation of a series of methyl 6‐[alkyl(aryl/heteroaryl)‐5‐trifluoromethyl‐1H‐pyrazol‐1‐yl] nicotinates as stable hydrochloride salts at 64–84% yields, which could be easily converted to hydrazides to give new oxadiazolyl‐pyrazolyl‐pyridine tricyclic scaffolds at good yields from a [4 + 1] cyclocondensation reaction with 1,1,1‐triethoxyethane and 1‐(triethoxymethyl)benzene as the reagent/solvent.     

Design and Synthesis of Novel Quinoline Tethered Tricyclic 1,5‐Benzothiazepine Derivatives via 1,3‐Dipolar Cycloaddition Reaction

A series of novel substituted‐[1,2,4]oxadiazolo[5,4‐d][1,5]benzothiazepine derivatives contain quinoline ring 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 5k , 5l were synthesized by the reaction of benzothiazepines 4a , 4b , 4c and substituted‐benzohydroximinoyl chlorides through the 1,3‐dipolar cycloaddition reaction in the presence of Et₃N at room temperature. The structures of the obtained adducts were elucidated by MS, IR, ¹H NMR, and elemental analyses. In addition, the structures of 5e were further confirmed by X‐ray single crystal diffraction study.     

Further Withaphysalin Derivatives from Acnistus arborescens

Two new epimeric chlorinated withaphysalins, rel‐(4β,5β,6α,18S,22R)‐ and rel‐(4β,5β,6α,18R,22R)‐6‐chloro‐18,20‐epoxy‐18‐ethoxy‐4,5‐dihydroxy‐1‐oxowitha‐2,24‐diene‐26,22‐lactone ( 1 and 2 resp.), together with the new rel‐(4β,5β,6α,18R,22R)‐6‐chloro‐18,20‐epoxy‐4,5‐dihydroxy‐18‐methoxy‐1‐oxowitha‐2,24‐diene‐26,22‐lactone ( 3 ) and rel‐(3β,4β,5β,6β,18R,22R)‐5,6:18,20‐diepoxy‐3,18‐diethoxy‐4‐hydroxy‐1‐oxowith‐24‐ene‐26,22‐lactone ( 4 ) were isolated from the leaves of Acnistus arborescens and named withaphysalins T–W, respectively. The final structures and the complete ¹H‐ and ¹³C‐NMR assignments of the three chlorowithaphysalins 1 – 3 were performed by means of HR‐ESI‐MS and 1D‐ and 2D‐NMR experiments, including COSY, HSQC, and HMBC, beside comparison with spectral data of analogous compounds from the literature. The structure of 4 was also confirmed by means of a single‐crystal X‐ray diffraction analysis.     

New Cell Growth-Inhibitory Cyclohexadienone Derivatives from Hypericum calycinum L.

The crude petroleum-ether extract of the aerial parts of Hypericum calycinum L. (Guttiferae) exhibited in vitro growth-inhibitory activity against the Co-115 human colon carcinoma cell line. Bioassay-guided fractionation of this extract allowed the isolation of the cyclohexadienone derivatives 1–5 , four of which are previously undescribed compounds. The structures of the known chinesin II (1) and of 2 (hypercalin A) were established by ¹H- and ¹³C-NMR spectroscopy and were confirmed by X-ray analysis of their crystalline mixture which revealed the complete relative configuration of both compounds. The structure of 3 (hypercalin B) was elucidated by means of extensive 1D- and 2D-NMR experiments, including DQ-COSY, HETCOR and LR-HETCOR. The structure of compound 4 (hypercalin C) was established by ¹H- and ¹³C-NMR spectroscopy and confirmed by X-ray analysis to be the 3,5-dihydroxy-4-{[(1R*,2S*, 5S*)-2-hydroxy-2-methyl-5-(1-methylethenyl)cyclopentyl]methyl}-6,6-bis-(3-methylbut-2-enyl)-2-(2-methylpropanoyl)cyclohexa-2,4-dien-1-one. The structures of the higher isomeric homologues 5a/5b were deduced by comparison of their UV, ¹H-, and ¹³C-NMR spectra with those of 4 . The isolated compounds appeared to be related to chinesin I and II previously isolated from Hypericum chinense L. and were responsible for the growth-inhibitory activity of the extract against the Co-115 human carcinoma cell line. Moreover, 1/2 and 3 showed molluscicidal activity against the schistosomiasis-transmitting snail Biomphalaria glabrata.