One‐Pot Regioselective Synthesis of Novel Oximino Ester‐Containing 1‐Aryl‐4‐chloro‐3‐oxypyrazoles as Potential Fungicides

A novel, functional‐group‐tolerant, and highly regioselective one‐pot synthesis of six 4‐chloro‐1‐aryl‐3‐oxypyrazoles, 8a – 8f , containing an oximino ester moiety has been developed. Their structures were characterized by ¹H‐ and ¹³C‐NMR, IR, MS, and elemental analyses. The regioselectivity of the reaction was also determined by single‐crystal X‐ray diffraction analysis of product 8d . The reaction pathway, proposed with the aid of DFT calculations, likely proceeds via a DMF‐catalyzed mechanism, which involves an electrophilic attack by SOCl₂ and two nucleophilic substitutions by benzyl bromide (BnBr) and Cl^?, respectively, as the key steps. A preliminary in vitro bioassay indicated that most compounds exhibited good fungicidal activities against Sclerotinia sclerotiorum and Gibberella zeae. Especially, 8d and 8e displayed higher or similar fungicidal activities compared with pyraclostrobin at the concentration of 10 μg/ml.     

Three New C19‐Diterpenoid Alkaloids from Aconitum forrestii

A further study of the alkaloid constituents of Aconitum forrestii led to the isolation of three new C₁₉‐diterpenoid alkaloids, named 14‐acetoxy‐8‐O‐methylsachaconitine ( 1 ), 14‐acetoxyscaconine ( 2 ), and 8‐O‐ethylcammaconine ( 3 ). Their structures were determined by UV, IR, and MS, 1D‐ and 2D‐NMR analyses.     

Purines. Part XVI

A series of N‐substituted 8‐aminoxanthines (=8‐amino‐3,7(or 3,9)‐dihydro‐1H‐purine‐2,6‐diones) 8 – 16 and 34 – 37 were synthesized from the corresponding 8‐nitroxanthines 1 – 7, 30 – 33 , and 8‐(phenylazo)xanthines 17 and 18 by catalytic reduction. Another approach was derived from 6‐amino‐5‐(cyanoamino)uracils (=N‐(6‐amino‐1,2,3,4‐tetrahydro‐2,4‐dioxopyrimidin‐5‐yl)cyanamides) 23, 24 , and 27 by base‐catalyzed cyclization yielding 25 – 28 . All 8‐aminoxanthines 8 – 29 and 34 – 37 were acetylated to the corresponding 8‐(acetylamino)xanthines 40 – 57 , and prolonged heating led to 8‐(diacetylamino)xanthines 58 and 59 . Several 8‐aminoxanthines 8 – 13 were diazotized forming 8‐diazoxanthines 60 – 64 . Coupling reactions of isolated 62 and 64 and intermediary formed 8‐diazoxanthines with 1,3‐dimethylbarbituric acid (=1,3‐dimethylpyrimidine‐2,4,6(1H,3H,5H)‐trione; 66 ) resulted in 5‐[(xanthin‐8‐yl)diazenyl]‐1,3‐dimethylbarbituric acids=3,7(or 3,9)‐dihydro‐8‐[2‐(1,2,3,4‐tetrahydro‐1,3‐dimethyl‐2,4‐dioxopyrimidin‐5‐yl)diazenyl]‐1H‐purine‐2,6‐diones) 67 – 80 . The newly synthesized xanthine derivatives were characterized by the determination of their pK_a values, the UV‐ and NMR spectra, as well as elemental analyses.     

Two New Limonoids from the Root Bark of Chinese Medicinal Plant Dictamnus dasycarpus

Two new limonoids, kihadanin C ( 1 ) and 23‐methoxydasylactone A ( 2 ), together with seven related known ones, 3 – 9 , were isolated from the root bark of the plant Dictamnus dasycarpus. The structures of the new compounds were elucidated on the basis of extensive analyses of their spectroscopic data (1D‐ and 2D‐NMR, MS) and by comparison of their NMR data with those reported in the literature. To the best of our knowledge, 1 presents the first example of A,D‐seco limonoid with an unusual 3,4‐dihydroxy‐2,5‐dimethoxytetrahydrofuran moiety as ring E. In the bioassay in vitro, 7 showed moderate antibacterial activity against Staphylococcus aureus, while 8 and 9 displayed neuroprotective activities against H₂O₂‐induced injury in SH‐SY5Y cells.     

A New Glycine Derivative and a New Indole Alkaloid from the Fermentation Broth of the Plant Endophytic Fungus Pestalotiopsis podocarpi Isolated from the Chinese Podocarpaceae Plant Podocarpus macrophyllus

A new glycine derivative, podocarpiamide ( 1 ), a new indole alkaloid, 1‐methoxy‐1H‐indol‐3‐ethanol ( 2 ), together with two known compounds, 1‐methoxy‐1H‐indole‐3‐acetic acid ( 3 ) and methyl 1‐methoxy‐1H‐indole‐3‐acetate ( 4 ), were isolated from the fermentation broth of the plant endophytic fungus Pestalotiopsis podocarpi. Their structures were elucidated by extensive spectroscopic analysis including 1D‐ and 2D‐NMR (HSQC, HMBC, and COSY) and MS experiments. Compound 1 has an interesting unusual carbamic acid structure.     

Two New Lycodine Alkaloids from Lycopodiastrum casuarinoides

Two new lycodine alkaloids, 11β‐methoxyhuperzine B ( 1 ) and 16‐oxohuperzinine ( 2 ), together with seven known ones, huperzinine N‐oxide, huperzine D, casuarinine A, huperzine B, casuarinine B, huperzinine, and N‐methyllycodine, were isolated from whole plants of Lycopodiastrum casuarinoides. Their structures were elucidated by spectroscopic methods, including NMR and MS experiments.     

Functionalization of Quinazolin‐4‐Ones Part 2#: Reactivity of 2‐Amino‐3, 4, 5, or 6‐Nitrobenzoic Acids with Triphenylphosphine Thiocyanate,Alkyl Isothiocyanates,and Further Derivatization Reactions

2‐amino‐3, 4, 5, or 6‐nitrobenzoic acids were reacted with PPh₃(SCN)₂ and alkyl isothiocyanates to give 5, 6, 7, or 8‐nitro‐2‐thioxo‐3‐substituted quinazolin‐4‐ones, respectively. The position of the nitro group was found to have significant influence on the outcome of the reactions. Similarly, the nature of the substituent at position 8 (NO₂, NH₂, NH(C═O)CH₃) in 8‐substituted‐2‐methylthio quinazolin‐4‐ones was also found to significantly influence their reactivity towards morpholine. A selection of the products were also tested for in vitro antibacterial activity but little activity was observed.     

A new coumarin from Perezia hebeclada

Methanol extracts from Perezia hebeclada roots yielded the new 8‐β‐D ‐glucopyranosyloxy‐4‐methoxy‐5‐methylcoumarin ( 1 ) together with the known 4‐β‐D ‐glucopyranosyloxy‐5‐methylcoumarin ( 2 ). Their structures were determined and verified, respectively, by MS and NMR studies, including 1D and 2D experiments. Two ¹³C NMR signals of the sugar residue of 2 were reassigned. Copyright © 2003 John Wiley & Sons, Ltd.     

Total assignments of 1H and 13C NMR spectra of a new prenylated flavanone from Dioclea grandiflora

A new prenylated flavanone, floranol ( 1 ) 3,5,7,2′‐ tetrahydroxy‐6‐methoxy‐8‐prenylflavanone and a known flavanone (dioclein) were isolated from the roots of Dioclea grandiflora (Fabaceae). The structure and the relative stereochemistry were established by 2D NMR spectroscopic techniques (HMQC and HMBC) Copyright © 2002 John Wiley & Sons, Ltd.     

Two New Steroidal Alkaloids from Veratrum nigrum L.

Phytochemical studies on Veratrum nigrum L., collected in Shanxi, P. R. China, resulted in the isolation of two new steroidal alkaloids, 23‐methoxycyclopamine ( 1 ) and 15‐O‐(2‐methylbutanoyl)‐3‐O‐veratroylprotoverine ( 2 ). The structures of the two new compounds were established by means of extensive NMR spectroscopic studies.     

New Lignans from the Roots of Taiwania cryptomerioides Hayata

The five new lignans designated 3′,4′‐de‐O‐methylenehinokinin ( 1 ), taiwaninolide ( 2 ), 8′‐hydroxysavinin ( 3 ), isoguamarol ( 4 ), and 4′‐O‐methylsalicifolin ( 5 ), as well as the new 4‐(3,4‐dimethoxybenzyl)dihydro‐3‐(4‐hydroxybenzyl)furan‐2(3H)‐one ( 6 ) were isolated from the roots of Taiwania cryptomerioides, besides the three known compounds hinokinin ( 8 ), savinin ( 9 ), and 3,4‐de‐O‐methylenehinokinin ( 7 ). The structures of the new constituents were elucidated through chemical and spectral studies. A compound previously isolated from the heartwood of Chamaecyparis obtusa var. formosana was assigned structure 1 ; however, this structure has now been revised to be 3,4‐de‐O‐methylenehinokinin ( 7 ).     

Zinc (II), palladium (II) and cadmium (II) complexes containing 4‐methoxy‐N‐(pyridin‐2‐ylmethylene) aniline derivatives: Synthesis,characterization and methyl methacrylate polymerization

A series of Zn (II), Pd (II) and Cd (II) complexes, [(L) _n MX ₂ ] _m (L = L‐a–L‐c; M = Zn, Pd; X = Cl; M = Cd; X = Br; n, m = 1 or 2), containing 4‐methoxy‐N‐(pyridin‐2‐ylmethylene) aniline ( L‐a ), 4‐methoxy‐N‐(pyridin‐2‐ylmethyl) aniline ( L‐b ) and 4‐methoxy‐N‐methyl‐N‐(pyridin‐2‐ylmethyl) aniline ( L‐c ) have been synthesized and characterized. The X‐ray crystal structures of Pd (II) complexes [L ₁ PdCl ₂ ] (L = L‐b and L‐c) revealed distorted square planar geometries obtained via coordinative interaction of the nitrogen atoms of pyridine and amine moieties and two chloro ligands. The geometry around Zn (II) center in [(L‐a)ZnCl ₂ ] and [(L‐c)ZnCl ₂ ] can be best described as distorted tetrahedral, whereas [(L‐b) ₂ ZnCl ₂ ] and [(L‐b) ₂ CdBr ₂ ] achieved 6‐coordinated octahedral geometries around Zn and Cd centers through 2‐equivalent ligands, respectively. In addition, a dimeric [(L‐c)Cd(μ ‐ Br)Br] ₂ complex exhibited typical 5‐coordinated trigonal bipyramidal geometry around Cd center. The polymerization of methyl methacrylate in the presence of modified methylaluminoxane was evaluated by all the synthesized complexes at 60°C. Among these complexes, [(L‐b)PdCl ₂ ] showed the highest catalytic activity [3.80 × 10⁴ g poly (methyl methacrylate) (PMMA)/mol Pd hr^?1], yielding high molecular weight (9.12 × 10⁵ g mol^?1) PMMA. Syndio‐enriched PMMA (characterized using ¹H‐NMR spectroscopy) of about 0.68 was obtained with T_g in the range 120–128°C. Unlike imine and amine moieties, the introduction of N‐methyl moiety has an adverse effect on the catalytic activity, but the syndiotacticity remained unaffected.     

The Synthesis and Chemistry of 1,3‐Bridged Polycyclic Cyclopropenes: 8‐Oxatricyclo[3.2.1.02,4]octa‐2,6‐dienes

Three 1,3‐bridged polycyclic cyclopropenes, exo‐8‐oxatricyclo[3.2.1.0^2,4]octa‐2,6‐diene ( 10 ), endo‐8‐oxatricyclo[3.2.1.0^2,4]octa‐2,6‐diene ( 11 ), and exo‐6,7‐benzo‐1,5‐diphenyl‐8‐oxatricyclo[3.2.1.0^2,4]octa‐2,6‐diene ( 12 ), have been synthesized by elimination of 2‐chloro‐3‐trimethylsilyl‐8‐oxatricyclo[3.2.1.0^2,4]‐oct‐6‐enes, 17 , 18 and 30 , which were generated from 1‐chloro‐3‐trimethylsilylcyclopropene with furan and diphenylisobenzofuran. We have demonstrated a facile route to synthesize the highly strained 1,3‐fused polycyclic cyclopropenes, 10 , 11 , and 12 . The stereochemistry of the Diels‐Alder reactions of cyclopropene 16 with furan and DPIBF are different. Cyclopropene 16 was treated with furan to form exo‐exo and endo‐exo adducts (5:2) and treated with DPIBF to generate an exo‐exo adduct. Compounds 10 , 11 and 12 undergo isomerization reactions to form benzaldehyde and phenyl 4‐phenyl‐[1]naphthyl ketone to release strain energies via diradical mechanisms.     

Synthesis and Characterization of Enantiomerically Pure cis‐ and trans‐3‐Fluoro‐2,4‐dioxa‐8‐aza‐3‐phosphadecalin 3‐Oxides as γ‐Homoacetylcholine Mimetics and Inhibitors of Acetylcholinesterase

The title compounds, the P(3)‐axially and P(3)‐equatorially substituted cis‐ and trans‐configured 8‐benzyl‐3‐fluoro‐2,4‐dioxa‐8‐aza‐3‐phosphadecalin 3‐oxides (=8‐benzyl‐3‐fluoro‐2,4‐dioxa‐8‐aza‐3‐phosphabicyclo[4.4.0]decane 3‐oxides=2‐fluorohexahydro‐6‐(phenylmethyl)‐4H‐1,3,2‐dioxaphosphorino[5,4‐c]pyridine 2‐oxides) were prepared (ee>98%) and fully characterized (Schemes 2 and 3). The absolute configurations were established from that of their precursors, the enantiomerically pure cis‐ and trans‐1‐benzyl‐4‐hydroxypiperidine‐3‐methanols which were unambiguously assigned. Being configuratively fixed and conformationally constrained phosphorus analogues of acetyl γ‐homocholine (=3‐(acetyloxy)‐N,N,N‐trimethylpropan‐1‐aminium), they are suitable probes for the investigation of molecular interactions with acetylcholinesterase. As determined by kinetic methods, all of the compounds are weak inhibitors of the enzyme.     

Furanone Derivatives from Aspergillus sp. XW‐12, an Endophytic Fungus in Huperzia serrata

Two new 5‐methoxyfuran‐3(2H)‐one derivatives, huaspenone A ( 1 ) and B ( 2 ), together with four known ones, i.e., aspertetronin A ( 3 ), aspertetronin B ( 4 ), gregatin E ( 5 ), and penicilliol A ( 6 ), were isolated from the cultures of an endophytic fungus Aspergillus sp. XW‐12, derived from the stems of Huperzia serrata. The structures of the new isolates were established by detailed interpretation of the 1D‐ and 2D‐NMR and HR‐ESI‐MS data.     

Two New Lycopodium Alkaloids from Lycopodium obscurum

Two new Lycopodium alkaloids, (+)‐cermizine D N‐oxide ( 1 ) and (8β)‐8‐(acetyloxy)obscurumine A ( 2 ), along with five known compounds, were isolated from the crude alkaloid portion of Lycopodium obscurum. Their structures were elucidated on the basis of spectroscopic data and chemical correlation. All of these alkaloids were tested in an assay for acetylcholine esterase (AChE) inhibitory activity.     

Stereoselective Synthesis of (2S, 8S)‐2‐Benzyl Hexahydro‐pyrrodizin‐3‐one Starting from (L)‐Proline Based on Stereoselective Benzylation

Abstract

A pyrrolizidine alkaloid, (2S, 8S)‐2‐benzyl hexahydro‐pyrrodizin‐3‐one, was synthesized from (L)‐proline using diastereoselective benzylation as the key step. The absolute configuration of the target compound was confirmed through 2D H‐H COSY and H‐H NOESY spectra.     

Steroidal Alkaloids from Veratrum maackii Regel with Genotoxicity on Brain‐Cell DNA in Mice

Two new steroidal alkaloids, 23‐methoxycyclopamine 3‐O‐β‐D ‐glucopyranoside ( 1 ) and isoecliptalbine ( 2 ), were isolated from the root and rhizoma of Veratrum maackii Regel , together with five known compounds, i.e., verussurine ( 3 ), verabenzoamine ( 4 ), verazine ( 5 ), isoverazine ( 6 ), and verazinine ( 7 ). Their structures were established by extensive analysis of spectroscopic data, as well as by comparison with literature data. Compounds 1 – 7 could cause DNA damage in the cerebellum and cerebral cortex of mice in a dose‐dependent manner by using single‐cell gel electrophoresis (comet assay).     

Xanthone O‐Glycosides from the Roots of Pteris Multifida

Two new xanthone glycosides and six known compounds were isolated from the roots of Pteris multifida. Based on spectroscopic and chemical methods, the structures of the new compounds were elucidated as 1‐hydroxy‐4,7‐dimethoxy‐8‐(3‐methyl‐2‐butenyl)‐6‐O‐α‐L‐rhamnopyranosyl‐(1→2)‐[β‐D‐glucopyranosyl‐(1→3)]‐β‐D‐glucopyranosylxanthone ( 1 ), and 1,3‐dihydroxy‐7‐methoxy‐8‐(3‐methyl‐2‐butenyl)‐6‐O‐α‐L‐rhamnopyranosyl‐(1 →2)‐[β‐D‐glucopyranosyl‐(1→3)]‐β‐D‐glucopyranosylxanthone ( 2 ), respectively.     

A new Sequiterpenoid from Eupatorium adenophorum Spreng

A new sequiterpenoid compound 8aα-hydroxy-1-isopropyl-4,7-dimethyl-1,2,3,4,6,8a-hexahydro-naphthalene-2,6-dione(1),together with seven known compounds anti-HH-dimer-coumarin(2),(-)-5-exo-hydroxy-bomeol(3),O-hydroxyl cinnamic acid(4),9β-hydroxy-ageraphorone(5),10Hα-9-oxo-ageraphorone(6),10Hβ-9-oxo-ageraphorone(7)and 9-oxo-10,11-dehydroageraphorone 8,was isolated from the leaves of Eupatorium adenopho-rum Spreng.The structures were elucidated by IR,~1H and ~(13)C NMR,EIMS,HMBC and single-crystal X-ray spec-tral data.