HETEROCYCLES

■ Contents

■ Reactivity of Zinc(II) 5-Oxonia-protoporphyrin-IX: Synthesis of the First 5-Oxonia-15-phlorin

Todd E. Clement, Benjamin Gerlach, Mathias O. Senge, and Kevin M. Smith*

*Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, CA 95616-5295, U.S.A.

Abstract

The reactivity of zinc(II) 5-oxoniaprotoporphyrin-IX with selected carbon nucleophiles is demonstrated to be highest at the 15-C_meso position, enabling the first synthesis of a 5-oxonia-15-phlorin which has been isolated and studied by X-Ray crystallpgraphy.

■ An Efficient Synthesis of 5-Phosphorylated 1,3,2-Diazaphosphinines from β-Functionalized Enamines Derived from Phosphine Oxides and Phosphonates

Francisco Palacios,* Domitila Aparicio, Jesús M. de los Santos, and Jesús García

*Departamento de Química OrgÁnica, Facultad de Farmacia, Universidad del País Vasco, Apartado 450, 01080 Vitoria-Gasteiz, Spain

Abstract

An easy and efficient synthesis of 1,3,2-P^III-diazaphosphininones (3,4) substituted with a phosphine oxide or a phosphonate group in the 5-position is described. The key step is a cyclocondensation reaction of substituted β-enamino amides (1) to phosphorus trichloride and phenylphosphonous dichloride. Subsequent treatment of 1,3,2-P^III-diazaphosphininones (3) with elemental sulfur, water or hydrogen peroxide afforded the substituted 2-thio-(7,8) and 2-oxo-1,3,2-P^V-diazaphosphininones (5,6,9).

■ The Diels-Alder Reaction of Phenylsulfonylacetylene and Furan Derivatives. Normal vs. Tandem 'Pincer' Reactions

Odón Arjona,* Fátima Iradier, Rocío Medel, and Joaquín Plumet*

*Departamento de Química Orgánica I., Facultad de Química., Universidad Complutense de Madridas, Ciudad Universitaria, E-28040 Madrid, Spain

Abstract

The Diels-Alder reaction between some furan derivatives and phenylsulfonylacetylene has been studied along the normal and ‘pincer’ pathways. The ring opening of some of the resulting products has been also examined.

■ H-D Exchange of Psilocin and Its Analogs

Kazuyo Sogawa, Kimiko Hashimoto, and Haruhisa Shirahama*

*School of Science, Kwansei Gakuin University, Uegahara, Nishinomiya 662-8501, Japan

Abstract

H-D exchange experiments were performed on psilocin (1) and its analogs in MeOH-d₄. The various exchange rates depending on their C3-substituents were observed. The exchange of bufotenine (5) and 5-hydroxyindole (7) is much slower than psilocin (1) and its analogs (2~4).

■ Diene-transmissive Hetero Diels-Alder Reaction of 1,5-Diphenyl-1,4-pentadien-3-one

Otohiko Tsuge,* Taizo Hatta, Toshitsugu Fujiwara, Tomoya Yokohari, Akihiko Tsuge, and Tetsuji Moriguchi

*Department of Applied Chemistry, Sojo University, 4-22-1, Ikeda, Kumamoto-shi, 860-0082, Japan

Abstract

The diene-transmissive hetero Diels-Alder reaction of 1,5-diphenyl-1,4-pentadien-3-one is described. Stereoselectivity of the inverse electron-demand Diels-Alder reaction of electron-rich vinyl ethers at the first stage was greately affected by the nature of Lewis acid-catalysts : The ZnX₂ (X=Cl, I)-, MgBr₂- and Eu(fod)₃-catalyzed reaction gave the corresponding endo-adducts, whereas exo-adducts were formed in the GaBr₃-, AlCl₃-, and Et₂AlCl-catalyzed reactions. In the sequential Diels-Alder reaction initial cycloadducts readily reacted with electron-deficient dienophile such as 1,2,4-triazolinedions, tetracyanoethene, and maleimides to give the corresponding cross-bis-cycloadducts.

■ One Pot Reaction of Unstable N-Acyl Quaternary Salt of Thiazoles or Imidazoles with Silyl Enol Ethers Formed in situ

Takashi Itoh, Michiko Miyazaki, Kazuhiro Nagata, Yûji Matsuya, and Akio Ohsawa*

*School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

Abstract

Ketone, trimethylsilyl triflate, triethylamine, thiazole or imidazole, and alkyl chloroformate were sequentially added to methylene chloride to form 2-substituted N-alkoxycarbonylated thiazoline or imidazoline derivatives in good yilds.

■ Novel Method for the Synthesis of Chiral 4-Aryl-γ-butyrolactones via Cascade Asymmetric Epoxidation—Ring Expansion—Baeyer-Villiger Reaction of Cyclopropylidene Derivatives

Masahiro Yoshida, Mohamed Abdel-Hamid Ismail, Hideo Nemoto, and Masataka Ihara*

*Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-5878, Japan

Abstract

Asymmetric epoxidation-ring expansion-Baeyer-Villiger reaction of cyclopropylidene derivatives using Oxone and fructose-derived ketone afforded chiral 4-aryl-γ-butyrolactones in one-pot process.

■ Enantioselective Synthesis of β-Amino Acid via Asymmetric Bromolactamization

Sang-sup Jew,* Kyung-hoi Cha, Sang-deog Kang, Yun-hee Woo, Hyung-ook Kim, and Hyeung-geun Park

*College of Pharmacy, Seoul National University, Shillim-Dong, San 56-1, Kwanak-Gu, Seoul 151-741, Korea

Abstract

Asymmetric bromolactamization using (S)-(-)-N-methoxy-2-pyrrolidine carboxamide (4) as a chiral auxiliary was performed successfully. The seven membered bromolactam obtained by asymmetric bromolactamization was converted to enantiomerically pure 3(S)-amino-2(R)-methylbutanoic acid (10).

■ Regiocontrolled Carbonylsulfanylations at ortho-Position of Phenols and at α-Position of Ketones Using Chlorocarbonylsulfenyl Chloride

Yoshihiro Yoshida, Masahiro Ogura, and Yoo Tanabe*

*School of Science, Kwansei Gakuin University, 1-1-155 Uegahara, Nishinomiya 662-8501, Japan

Abstract

Bu₃N/AlCl₃-promoted [3+2] cyclocondensation between phenols and chlorocarbonylsufenyl chloride (CCSC ; 3) gave 1,3-benzoxathiol-2-ones (2), wherein the acylation of phenols with CCSC (3) and the intramolecular and regioselective ortho-sulfenylation successively proceeded in a one-pot manner. 2-Sulfanylphenols (1) were produced from 2 by mild hydrolysis using NaOH. An analogous Bu₃N-promoted [3+2] cyclocondensation between ketones and 3 gave 1,3-oxathioles (7), wherein the α-CH₂- position of the ketones was regioselectively sulfenylated.

■ Synthesis of Triazolo[4,5-f]quinolines. An Unusual Case of Displacement of Nitro Group in the Reaction of 8-Acetylamino-6-chloro-5-nitroquinoline with Hydrazine and Methylhydrazine

Paolo Sanna,* Antonio Carta, and Giuseppe Paglietti

*Dipartimento Farmaco Chimico Tossicologico, Universita di Sassari, Via Muroni 23/a, 07100 Sassari, Italy

Abstract

Nitration of 1H-, 3-methyl- and 2-methyltriazolo[4,5-f]quinolines (6a-c) as a way to obtain the desired 4-aminotriazolo[4,5-f]quinolines (4) for a medicinal chemistry project was successful only in the case of 6c. Attempted building up of the triazole ring starting from 8-acetylamino-6-chloro-5-nitroquinoline (8) with ammonia, hydrazine and methylhydrazine at 150°C in ethanol failed. However, the results obtained from these reactions allowed us to observe that, during nuclephilic aromatic substitution of chlorine by these bases an unusual displacement of the nitro group by hydrogen occurred. Comparison of these results with those obtained using different substrates allowed us to evaluate the influence of both para-acetylamino group and pyridine ring in this type of nucleophilic aromatic substitution.

■ First Synthesis and Crystal Structures of Chiral 1,3-Dienylborates

Jacques Mortier,* Michel Vaultier, Barbara Plunian, and Loïc Toupet

*Université Rennes-I, Synthèse et èlectrosynthesse organiques, UMR 6510 Associée au CNRS, Campus de Beaulieu, 35042 Rennes Cedex, France

Abstract

We repot on the synthesis of bicyclic 1,3-dienylborates (1a/1b and 2a/2b), wherein the boron and nitrogen atoms are chiral. The absolute configuration of these molecules was established by single X-Ray diffraction studies and qualitative homonuclear NOE difference spectroscopy. The conformational stability of these molecules is low at ambient or subambient temperature. The diastereomeric borates (2a/2b) were found to be very reactive toward dienophiles in the Diels-Alder reaction.

■ Formation of Bicyclic β-Lactams from Dichloro-1,4-oxathiane-3-carboxanilides: Nucleophilic Substitution of Nitrogen on Anomeric Carbon

Hoh-Gyu Hahn* and Kee-Hyuk Chang

*Organic Chemistry Laboratory, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650, Korea

Abstract

Transformation of dichloro-1,4-oxathiane anilides (2) to bicyclic β-lactam (5) is described. In the presence of sodium hydride, an intramolecular nucleophilic substitution of nitrogen to anomeric carbon of 2 gave (1R,6R)-1-chloro-6-methyl-7-phenyl-5-oxa-2-thia-7-azabicyclo[4,2,0]ocata-8-ones (5). The reason for facile displacement at C-2 is attributable to neighboring group participation of sulfur and C-2 is anomeric. Plausible mechanisms for the formation of 2-chloromethyl-5-,6-dihydro-N-phenyl-1,4-oxathiin-3-carboxyamide (4) under the neutral conditions, or 2,3-dihydroxy-2-methyl-N-phenyl-1,4-oxathiane-3-carboxyamide (9) in aqueous solution, or bicyclic β-lactam (5) in the presence of sodium hydride were proposed.

■ β-Glucosyltransferase in Cell Cultures of Verbesina caracasana

Alberto Vitali, Giuliano Delle Monache,* Giovanni Zappia, Domenico Misiti, Eszter Gacs-Baitz, and Bruno Botta*

*Centro Chimica dei Recettori, C.N.R., Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Roma, Italy

Abstract

(E)-3,4-Dimethoxycinnamic acid, inoculated in cell cultures of Verbesina caracasana, was converted to the corresponding β-glucopyranoside ester, reveling the presence of an exoglucosyltransferase. An extensive study on other cinnamic acid derivatives showed that the aromatic ring must contain at least one methoxy substituent, but no hydroxy group, for the esterification to be performed. Moreover, the presence of the double bond was shown to have no influence. The glucosylation reaction may involve also the hydroxyl of benzyl alcohols, with the same specificity towards the substitution of the aromatic ring as shown by the cinnamic acids.

■ A Radical Route to Morphans. Synthesis and Spectroscopic Data of the 2-Azabicyclo-[3.3.1]nonane

Josefina Quirante, Carmen Escolano, Faïza Diaba, and Josep Bonjoch*

*Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Av. de Joan XXIII, s/n, 08028 Barcelona, Spain

Abstract

The synthesis of 1-benzyl-2-azabicyclo[3.3.1]nonan-3-one (8) through radical cyclization, involving an intramolecular addition of a carbamoyl-dichlomethyl radical upon an alkene, is described. Conversion of 8 to the morphan itself, and the spectroscopic analysis of some derivatives of this series are reported.

■ Cyclization of Tautomeric 1,5-Dinitrile Systems with Hydrogen Halides: A Definitive Mechanistic Rationalization?

Jordi Teixidó,* José I. Borrell, Blanca Serra, Josep Lluis Matallana, Carles Colominas, Francisco Carrión, Rosalia Pascual, Josep Lluis Falcó, and Xavier Batllori

*Departament de Química Orgànica, CETS Institut Quimic de Sarrià, Universidad Ramon Llull, Via Augusta 390, E-08017 Barcelona, Spain

Abstract

A new mechanistic rationalization for the cyclization with hydrogen halides of tauomeric 1,5-dinitriles of general structure (10) (Z=N), (14)(Z = C-CN), (16) (Z=N), and (18) (Z = C-CN) is proposed (Scheme 5). In such rationalization, three factors play a major role on the direction of cyclization : Position of the equilibrium of the tautomeric 1,5-dinitrile system, relative basicity of the cyano group involved, and planarity of the reaction zone.

■ Peroxidase from Cell Cultures of Cassia didymobotrya: A Review and Comparison with Horseradish Peroxidase

Bruno Botta,* Paola Ricciardi, Alberto Vitali, Vittorio Vinciguerra, Carlos Garcia, and Giuliano Delle Monache*

*Centro Chimica dei Recettori, C.N.R., Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Roma, Italy

Abstract

The catalytic activity on flavonoids and dibenzylbutanolides and the specificity of the peroxidase isolated from 29d-old cell cultures of Cassia didymobotrya are repoted. Studies in several substrates in Comparison with horseradish peroxidase revealed peculiar activities and suggested the enzyme to be involved in the lignification process.

■ Synthesis of N-(Arylprop-2-en-1-yl)benzotriazoles by the Heck Reaction

Alan R. Katritzky,* Abd El-Rahman S. Ferwanah, and Sergey N. Denisenko

*Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, P. O. Box 117200, Gainesville, FL 32611-7200, U.S.A.

Abstract

Various substituted 1-prop-2-en-1-ylbenzotriazoles react with aryl halides under Heck reaction conditions to give the corresponding alkenylbenzotriazole derivatives (10a-m). These are useful synthons for the preparation of dienes, β,γ-unsaturated ketones, alcohols and amines.

■ Studies on a Total Synthesis of Plakotenin: Synthesis of Optically Active trans-Hydrindanes by Diastereoselective Asymmetric Intramolecular Diels-Alder Reaction

Miyuki Ishizaki, Yasuhiro Hara, Sachiko Kojima, and Osamu Hoshino*

*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 12, Ichigaya Funagawara-machi, Shinjuku-ku, Tokyo 162-0826, Japan

Abstract

Diastereoselective asymmetric intramolecular Diels-Alder reaction of 5,5-(trimethylenedithio)-2(E),7(E),9-decatrienoyl amides (13a-e) having various chiral auxiliaries was performed to give optically active trans-hydrindanes, which would be an important intermediate for a total synthesis of plakotenin (1), was described. In the several chiral auxiliaries, Saigo's oxazolidinone was found to give trans-hydrindane (15a) in the highest stereoselectivity (96% e.e.), after conversion to benzyl ester.

■ Reaction of β-Cyanomethylene-β-enamino Diketones and -keto Esters with Hydrazines: Synthesis of Pyrazole and Pyridine Derivatives

Chiara B. Vicentini, Maurizio Manfrini, Manuela Mazzanti, and Augusto C. Veronese*

*Dipartimento di Scienze Farmaceutiche, Universita di Ferrara, via Fossato di Mortara 17, I-44100, Ferrara, Italy

Abstract

4-Acetyl-3-amino-5-oxo-3-hexenenitrile (1a) reacts with hydrazines to give pyrazolyl enaminonitriles (2) while 2-acetyl-3-amino-4-cyano-2-butenoic avid methyl ester (1b) reacts with hydrazines to give pyridine derivatives (6) or (7).

■ 4-Acyl-5-methyl-2-phenylpyrazolones: NMR and X-Ray Structure Investigations

Wolfgang Holzer,* Kurt Mereiter,* and Brigitte Plagens

*Institute of Pharmaceutical Chemistry, University of Vienna, Pharmaziezentrum, Althanstrasse14, A-1090 Vienna, Austria

Abstract

¹H- and ¹³C-NMR investigations with 4-acyl-5-methyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-ones (1-6) are presented, indicating these compounds to exist predominantely as hydroxypyrazoles in CDCl₃ or benzene-d₆ solution, whereas in DMSO-d₆ also a considerable amount of NH tautomer is present. X-Ray crystal analyses revealed that in the solid state the 4-propionyl compound (2) is present as hydroxypyrazole, the 4-(2-thienyl) derivative (6) as NH isomer and the 4-cinnamoyl product (4) to have an exocyclic double bond structure stabilized by an intramolecular hydrogen bond. Cyclisation of the latter compound (4) in acidic medium leads to the formation of 3-methyl-1,6-diphenyl-5,6-dihydro-1H-pyrano[2,3-c]pyrazol-4-one (7) in very low yields.

■ Substituted Benzimidazoles. Part 2. Synthesis and Properties of 2-Aryl-1-hydroxy-5-(2-thenoyl)benzimidazole 3-Oxides

Marwan R. Kamal,* Mustafa M. El-Abadelah, Amer A. Mohammad, and Herbert Meier

*Chemistry Department, Faculty of Science, University of Jordan, Amman 11942, Jordan

Abstract

A selected set of 2-aryl- and 2-hetaryl-1-hydroxy-5-(2-the-noyl)benzimidazole 3-oxides (10a-m) was prepared for bioassay via condensation dioxime (8) as catalyzed by perchloric acid. The dioxime (8) was obtained by facile reduction of 5-(2-thenoyl)benzofuroxan (7a) with 1,2-diphenylhydrazine. The furoxans (7a,b) are accessible by pyrolysis of the respective o-nitrophenyl azides (6a,b). Compounds (10a-g) showed a comparable range of in vitro activity against Escherichia coli and Candida albicans (MIC 62.5-125μg/mL).

■ A New Divergent Asymmetric Synthesis of (+)- and (-)-Ethosuximides and Their Anti-Convulsant Activities

Takahiro Katoh, Kiyoharu Nishide, Manabu Node,* and Hiroo Ogura

*Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan

Abstract

Both enantiomers of ethosuximide were synthesized divergently from nitroolefin lactone [(-)-2a] or [(-)-2b], which was obtained by asymmetric nitroolefination of α-methyl-γ-butyrolactone with chiral nitro enamines derived from L-proline. Although anticonvulsant activity was confirmed in both enantiomers, the (S)-ethosuximide was more active than the (R)-enantiomer.

■ The Reaction of 5-Chloro Derivatives of 3-Pyridinol and 3-Methoxypyridine with Various Amines under Aryne-forming Conditions

Sagun Tandel and Edward R. Biehl*

*Department of Chemistry, Dedman College, Southern Methodist University, P.O.Box 750314, Dallas, Texas 75275-0314, U.S.A.

Abstract

The reactions of 5-chloro-3-pyridinol (1) and 5-chloro-3-methoxypyridine (6) with various lithium amides (2') in THF or free amine solvent (2) have been studied and the results reported herein. In most cases, 5-aminated products were exclusively formed ; however, in the reaction of 1 with LDA or n-butylamine, 4-aminated products were formed predominantly. Additionally, and without exception, aminated products were obtained in highest yields when the reactions were carried out in the corresponding free amine solvents.

■ Ethyl 2-(2-Acetyl-2-ethoxycarbonyl-1-ethenyl)amino-3-dimethylaminopropenoate in the Synthesis of Heterocyclic Systems. The Synthesis of Substituted 3-Aminoazolo- and -azinopyrimidinones, Pyridopyridinones and Pyranones

Renata Toplak, Mitja Zucchiati, Simona Golic Grdadolnik, and Branko Stanovnik*

*Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, P.O. Box 537, SLO-1000 Ljubljana, Slovenia

Abstract

Ethyl 2-(2-acetyl-2-ethoxycarbonyl-1-ethenyl)amino-3-dimethylaminopropenoate (2) was prepared from ethyl N-(2-acetyl-2-ethoxycarbonyl-1-ethenyl)glycynate (1) and N,N-dimethylformamide dimethyl acetal, and used as a reagent for preparation of substituted amino azolo- and azinopyrimidin-4-ones (16-20), quinolizin-4-ones (31 and 32 ), 2H-1-benzopyran-2-ones (33), and isomeric naphthopyranones (34-37), 2H-pyrano[2,1-b]pyridine-2,5-dione (38), pyrano[4,5-b]pyran-2,5-dione (39) and pyrano[3,2-c]bezopyran-2,5-dione (40).

■ Synthesis and Biological Activity of 1-Cyclopropyl-1,4-dihydro-4-oxo-3-pyridinecarboxylic Acid

Hans Rudolf Pfaendler* and Wolfgang Jenni

*Institute of Organic Chemistry, University of Munich, Karlstrasse 23, D-80333, München, Germany

Abstract

1-Cyclopropyl-1,4-dihydro-4-oxo-3-pyridinecarboxylic acid was prepared in four reaction steps and tested for antibacterial activity.

■ Preparation of 4-Iodo-β-carboline-3-carboxamide via ortho-Metalation and Its Use in Palladium-catalyzed Carbon-Carbon Bond Forming Reactions with Unsaturated Substrates

Alexandre Batch and Robert H. Dodd*

*Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, Avenue de la Terrasse, Bat. 27, 91198 Gif-sur-Yvette Cedex, France

Abstract

The 4-iodo derivative of N-9 protected β-carboline-3-(N-methyl)-3-(N-phenyl)carboxamide (12) was prepared by sequential treatment of N-9 protected β-carboline-3-(N-phenyl)carboxamide (2) with methyllithium, iodine and methyl iodide. Compound (12), in the presence of catalytic palladium acetate and tri-o-tolylphosphine in acetonitrile and triethylamine, reacted with a variety of unsaturated substrates (styrenes, acrylate, tributyl(vinyl)tin, trimethylsilylacetylene) to give the corresponding C-4 coupled adducts (13a-g).

■ Polycylic N-Heterocyclic Compounds. 53. One Step Synthesis of Imidazo[1,5-a]pyridine Derivatives by Vilsmeier Reaction Using N,N-Dimethylarylamides

Kenji Sasaki, Akifumi Tsurumori, Setsuo Kashino, and Takashi Hirota*

*Faculty of Pharmaceutical Science, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan

Abstract

The versatile one step synthesis of 3-ary-1-(C-aryl-N,N-dimethylaminomethyleneamino)-7-chloro-2-methylimidazo[1,5-a]pyridin-2-ium chloride and their derivatives by the reaction of 2-pyridinecarbonitriles with N,N-dimethylarylamides and phosphorus oxychloride under the Vilsmeier condition is described. The structures are based upon characteristic spectra and analytical data as well as X-Ray diffraction.

■ 10-Hydroxy-7-arylindeno[1,2-b]-1,2,5-oxadiazolo[3,4-d]pyridines and 7-Aryl-10-oxoindeno[1,2-b]-1,2,5-oxadiazolo[3,4-d]pyridines— Synthesis, Spectra, and Polymorphism

Shuntaro Mataka,* Hideki Gorohmaru, Thies Thiemann, Tsuyoshi Sawada, Kazufumi Takahashi, and Akiyoshi Tori-i

*Instituete of Advanced Material Study, Kyushu University, 6-1, Kasuga-koen, Kasuga 816-8580, Japan

Abstract

The novel dyes 7-aryl-10-oxoindeno[1,2-b]-1,2,5-oxadiazolo[3,4-d]pyridines (4) and 7-aryl-10-hydroxyindeno[1,2-b]-1,2,5-oxadiazolo[3,4-d]pyridines (5) have been prepared from acetophenone derivatives. While compounds (4) exhibit a dark red color, they are only weakly fluorescent. Compounds (5) is fluorescent. Of interest is that 10-hydroxy-7-phenylindeno[1,2-b]-1,2,5-oxadiazolo[3,4-d]pyridine(5a)can take four polymorphic forms in the solid state, of which two are yellow (designated as 5a-Y-1 and 5a-Y-2) and two are red (5a-R-1 and 5a-R-2). Two of them are interconvertible (yellow/red) upon exposure to different solvents. X-Ray crystal structure analysis of 5a-R-2 shows the phenyl ring and the indenooxadiazolopyridine ring to be coplanar.

■ The Isolation and Structure of Pumiliotoxin 341A: A Novel Cyclic Ether from the Frog Epipedobates tricolor

Poonam Jain, Thomas F. Spande, H. Martin Garraffo, and John W. Daly*

*Laboratory of Bioorganic Chemistry, Bldg. 8, 1A15, National Institute of Health, 8 Center Drive MSC 0820, Bethesda, MD 20892, U.S.A.

Abstract

An alkaloid 341A isolated by HPLC from skim extracts of the Ecuadoran poison frong Epipedobates tricolor was characterized by FTIR, MS and ¹H-NMR spectral analysis and assignet a spiro-fused pyranoindolizidine structure (1). It represent the first member of a small group of pumiliotoxin alkaloids to contain a cyclic ether moiety.