HETEROCYCLES

■ Hypoestoxide, a New Diterpene from Hypoestes rosea (Acanthaceae)

Akinbo A. Adesomoju, Joseph I. Okogun, Michael P. Cava, and Patrick J. Carroll

*Department of Chemistry, University of Pennsylvania, 231 South 34th Street Philadelphia, PA 19104-6323, U.S.A.

Abstract

Hypoestoxide, a new diterpene from Hypoestes rosea (Acanthaceae) has been assigned the bicyclo[9,3,1]pentadecane structure 1.

■ A Short Synthesis of 2,2-Disubstituted Benzo[a]quinoline and indolo[2,3-a]quinolizine Derivatives via Carbon-Fragment Transfer from a Folic Acid Model

Axel R. Stoit and Upendra K. Pandit

*Organic Chemistry Department, University of Amsterdam, Nieuwe Achtergracht 129, 1018 WS Amsterdam, The Netherlands

Abstract

1-Tosyl-2-(3’-ethoxycarbonyl-3’-methyl-2’-oxo)butyl-3,4,4-trimethyl-2,3-imidazolidine — a substituted methylenetetrahydrofolate model — serves as a reagent for the transfer of the 2,2-dimethyl-3-oxo-4-methenylbutanoate moiety to 2-arylethylamine and tryptamine to give products which can be converted to benzo[a]quinolizine and indolo[2,3-a]quinolizine derivatives, respectively, in two simple steps.

■ Intramolecular 1,3-Dipolar Cycloadditions of Benzylidene-α-cyanobenzylamines Bearing Non-activated Alkynyl and Alkenyl Functions

Otohiko Tsuge and Kazunori Ueno

*Research Institute of Industrial Science, Faculty of Engineering, Kyushu University, 6-1, Kasuga-koen, Kasuga 816-8580, Japan

Abstract

Benzylidene-α-cyanobenzylamine systems undergo an intramolecular cycloaddition via their 1,3-dipolar tautomers, azomethine ylides, to non-activated alkynyl and alkenyl functions, and give mainly dehydrocyanated fused heterocycles.

■ A Novel Synthesis of Quinazolines and 1,4-Benzodiazepines

Jan Bergman, Anna Brynolf, and Björn Elman

*Department of Organic Chemistry, Royal Institute of Technology, SE-100 44 Stockholm, Sweden

Abstract

The synthesis of 1,4-benzodiazepines and quinazolines from o-aminobenzonitriles is reported. For the formation of the 1,4-benzodiazepines a mechanism involving an intermediate aziridinone is proposed.

■ The Synthesis, Separation and Structure Determination of Two Conformers of 2,2-Dimethyl-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-3-one

Jan Bergman, Anna Brynolf, Karl-Wilhelm Törnroos, Bengt Karlsson, and Per-Erik Werner

*Department of Organic Chemistry, Royal Institute of Technology, SE-100 44 Stockholm, Sweden

Abstract

3,3-Dimethyl-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-3-one has been synthetized by interaction of C₆H₅MgBr with α-bromo-α,α-dimethyl-2-cyanoacetanilide. Two conformers of the product were isolated and their structures determined by X-ray crystallography.

■ A Comment on Lead Tetraacetate Oxidation of Four Guiacol-type 1,2,3,4-Tetrahydroisoquinolines

Hiroshi Hara, Hiroshi Shinoki, Osamu Hoshino, and Bunsuke Umezawa

*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan

Abstract

Lead tetraacetate oxidation of four guiacol-type tetrahydroisoquinolines (1a, 2a, 6, and 7a) in CH₂Cl₂ at 0 °C gave the respective o-quinol acetates (4a, 12, 8, and 13). On the other hand, oxidation of them in AcOH at room temperature afforded the acetoxy derivatives (14a, 3a, 9, and 14a), respectively. Treatment of the o-quinol acetate (4a, 12, 8, or 13) with AcOH yielded the same product (14a, 3a, 9, or 14a) as above. The o-quinol acetate (4a or 13) was thermally transformed into the 4-acetoxy derivative (5a or 15).

■ A Synthesis of 3-Hydroxyaporphine and Homoaporphine

Hiroshi Hara, Hiroshi Shinoki, Osamu Hoshino, and Bunsuke Umezawa

*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan

Abstract

3-Hydroxy-2,9,10-trimethoxyaporphine (8) and 3-hydroxy-2,10,11,12-tetramethoxyhomoaporphine (9) were synthesized via the corresponding o-quinol acetates (13 and 14).

■ A New Synthesis of Steroid Side Chain via Stereocontrolled Protonation: Synthesis of Naturally Occurring Methyl (20S)-3β-Hydroxycholenates

Seiichi Takano, Hirotoshi Numata, Shin’ichi Yamada, Susumi Hatakeyama, and Kunio Ogasawara

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

Protonation of the steroidal γ-lactone enolate (10), obtained from the 20-cyano steroid (2) and (S)-benzyl 2,3-epoxypropyl ether (S-1), with saturated aqueous sodium sulfate affords the 20(R)-lactone (9a) as a major isomer which is then converted into methyl (20S)-3β-hydroxycholenates (19) and (22) isolated from a sea pen, Ptilosarcus gurneyi.

■ Heterocyclic Substituted Amino Acids via α,β-Dehydroamino Acid Derivatives. Studies on Amino Acids III

Claus Herdeis and Ulrich Nagel

*Institut für Pharmazie und Lebensmittelchemie, Universität München, Sophienstraße 10, D-80333 München, Germany

Abstract

Condensations of lactam acetals 2a,b with isocyanacetic esters give 3a,b. The Z-configuration of 3a (R₁=CH₃, R₂=C₂H₅) was determined by X-ray diffraction. Reaction with ethyl N-(ethoxycarbonyl)glycinate gives the protected α,β-dehydroamino acid derivatives 4. The isocyano group can be converted to the carbamate group via the isocyanates 5. Catalytic hydrogenation of the double bond and deprotection of the functional groups give the amino acids 11a, b and 10.

■ Reactions of 6-Methoxy-3-azabicyclo[4.2.0]octan-2-one and Its 7-Substituted Derivatives

Chikara Kaneko, Yu Momose, Tsuyoshi Maeda, Toshihiko Naito, and Masanori Somei

*Faculty of Pharmaceutical Scicences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan

Abstract

The mechanisms of two synthetically useful reactions using photoadducts obtained from 4-methoxy-2-pyridone and a variety of olefins as key intermediates, namely the cyclobutane-annelation and isoprenylation to 2-pyridone, have been clarified using the dihydro derivatives of these adducts (6-methoxy-3-azabicyclo[4.2.0]octan-2-ones) as the starting materials. A possible extension of these two methods to aliphatic enone series is suggested.

■ Synthesis of the First Examples of N-Unsubstituted 1,3-Benzodiazepines

Jyoji Kurita, Michiko Enkaku, and Takashi Tsuchiya

*School of Pharmacy, Hokuriku University, 3-Ho, Kanagawa machi, Kanazawa 920-1181, Japan

Abstract

Treatment of both 3-benzyloxycarbonyl-3H-1,3- (6) and 1-benzyloxycarbonyl-1H-1,3-benzodiazepine (9) with trimethylsilyl iodide resulted in decarboxylation to give the N-unsubstituted 3H-1,3-benzodiazepine hydroiodide (8), which, on treatment with base, yielded the free bases (11). The 1,3-thienodiazepines (14) and (15) gave similar results. These results may indicate that the 3H-tautomers are most stable in the possible three 1,3-benzodiazepine tautomers.

■ A Simple Synthesis of 1,3-Dialkylpyrido[2,3-d]pyrimidines

Tsuneo Itoh, Toshihiko Imini, Haruo Ogura, Norio Kawahara, Takako Nakajima, and Kyoichi A. Watanabe

*School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan

Abstract

A novel and simplified synthesis of 1,3-dialkylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones from 6-allylamino- and 6-(substituted allyl)aminouracils by PdCl₂-CuCl catalyzed oxidative cyclization is described.

■ A Formal Total Synthesis of (±)-Carpetimycin A (C-19393 H₂): Stereoselective Synthesis of (±)-cis-4-Carboxymethyl-3-(1-methyl-1-trimethylsilyloxyethyl)-2-azetidinone via an Isoxazoline Derivative

Masataka Ihara, Fujiko Konno, Keiichiro Fukumoto, and Tetsuji Kametani

*Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

The synthetic intermediate, (±)-cis-4-carboxymethyl-3-(1-methyl-1-trimethylsilyloxyethyl)-2-azetidinone (10), of the carbapenem antibiotics, carpetimycin A, was stereoselectively prepared via an isoxazoline derivative (3).

■ 1-Methyl-2-azathiabenzene 1-Oxide: Synthesis and Some Properties

Masazumi Ikeda, Hidetsugu Tsubouchi, Masayoshi Tsunekawa, Hiroshi Kondo, and Yasumitsu Tamura

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

Abstract

Synthesis and some properties (¹H- and ¹³C-NMR spectra, deuteration, nitration, and cycloaddition) of 1-methyl-2-azathiabenzene 1-oxide are described.

■ New Synthetic Approaches to 4(1H)-Pyridinone Derivatives. The Synthesis of 3-Acyl-4(1H)-pyridinones

Raiz F. Abdulla, Lawrence A. Morgan, and James C. Williams, Jr.

*Lilly Reserach Laboratories, Lilly Corporate Center, Eli Lilly & Company, Indianapolis, IN 46285-4813, U.S.A.

Abstract

The synthesis of 3-alkanoyl and 3-benzoylpyridin-4-one is described from 1,3-diketones (5,11) or their equivalents. A novel C_α¹-acylation of enaminones is described.

■ Reaction of 1-Methyl-Δ¹⁽⁸⁾-dehydropyrrolizidine with Dimethyl Acetylenedicarboxylate

Seiji Miyano, Nobuko Mibu, Shinichiro Fujii, Osamu Yamashita, Hirokazu Annoura, and Kunihiro Sumoto

*Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

Abstract

The reaction of 1-methyl-Δ¹⁽⁸⁾-dehydropyrrolizidine with dimethyl acetylenedicarboxylate in hexane gave dimethyl 7-methyl-1,2,5,6-tetrahydro-3H-pyrrolo[1,2-a]azepine-8,9-dicarboxylate (3a) and dimethyl 1-methyl-1,2,5,6-tetrahydro-3H-pyrrolo[1,2-a]azepine-8,9-dicarboxylate (4a). The choice of protic solvent like methanol gave rise to the formation of a tricyclic compound.

■ Carbon-13 Nuclear Magnetic Resonance Spectra of 2-Arylidene-3(2H)-benzofuranones

Aurora Bellino, Maria Luisa Marino, and Pietro Venturella

*Instituto de Chimica Organica , Facolta de Scienze, Università digli Studi di Palermo, 20 via Archirafi, 90123 Palermo, Italy

Abstract

¹³C-NMR spectra of a variety of 2-arylidene-3(2H)-benzofuranones are reported. Are examined the chemical shifts and is discussed the way in which the substituent effects can be used for elucidation of structure.

■ The Acidities and the Tautomeric Structure of 5-Aryl-2-mercapto-1,3,4-oxadiazoles

Ahmad S. Shawali, Mahmoud S. Rizk, Abdou O. Abdelhamid, Magda A. Abdalla, Cyril Párkányi, and Magdalena E. Wojciechowska

*Department of Chemistry, The University of Texas at El Paso, El Paso, Texaz 79968-0513, U.S.A.

Abstract

The acidity constants of a series of substituted 5-phenyl-2-mercapto-1,3,4-oxadiazoles were determined by potentiometric and spectrophotometric methods in 80% (vol.) ethanol-water at 25 °C. The data obtained by the two methods are in good agreement. The pK_a values correlate with the σ*_XC6H4 constants of the substituted phenyl group (ρ = -0.985, r = 0.936), however, a better correlation of the pK_a data with the Hammett substituent constants σ_X (ρ = -0.983, r = 0.959) was obtained. These linear correlations exclude the possibility of the presence of the thiol tautomer 1 in equilibrium with the thioamide tautomer 2 and indicate that the ionization of the compounds takes place in the form of the thioamide tautomer 2. According to the results of the HMO calculations, the thioamide form 2 is more stable than the thiol tautomer 1. A satisfactory correlation between the observed pK_a values and the difference between the π-electronic energies (ΔE_π) of the thioamide tautomer and of the common resonance-stabilized anion was obtained, thus supporting the assigned tautomeric structure 2 for the series under study.

■ Synthesis of Some Pyrimido[1,2-b]pyridazin-2- and -4-ones. Studies on Pyridazine Compounds, XV.

Péter Mátyus, Endre Kasztreiner, Géza Szilágyi, Márta Sóti, and Pál Sohár

*Institute for Drug Research Ltd., H-1325 Budapest, POB 82, Hungary

Abstract

Same pyrimido[1,2-b]pyridazin-2- and -4-ones were synthesized. On the basis of their spectral data the structure of some known derivatives is revised.

■ Thermal Decomposition of Dihydroergocristine Methanesulphonate

Rudolf Rucman and Branko Stanovnik

*Department of Chemistry, E. Kardelj University, Murnikova 6, 61000 Ljubljana, Slovenia

Abstract

By thermal decomposition of dihydroergocristine methanesulphonate (1a.CH₃SO₃H) are formed dihydrolysergyldehidrovaline methyl ester (2), dihydrolysergyldehydrovaline azlactone (3c), dihydrolysergic acid (3a). dihydrolysergamide (3b), S-phenylalanyl-S-proline lactam (4a) and S-phenylalanyl-R-proline lactam (4b).

■ Reactions of Isocyanates with Ethyl 2-Amino-1-cyclopentene-1-carboxylate

Else Marie Jensen and Eleftherios Paul Papadopoulos

*Department of Chemistry, University of New Mexico, Albuquerque, NM 87131, U.S.A.

Abstract

Aromatic isocyanates react with ethyl 2-amino-1-cyclopentene-1-carboxylate to yield the corresponding ureas, which cyclize by base to 3-substituted 6,7-dihydro-1H-cyclopentapyrimidine-2,4(3H,5H)-diones.

■ Conversion of Methylenedioxybenzene Derivatives into 2-Methoxyphenol Derivatives

Seiichi Takano, Masashi Akiyama, and Kunio Ogasawara

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

Methylenedioxybenzene derivatives are reductively cleft with diisobutylaluminum hydride to give 2-methoxyphenol derivatives. Concurrent hydroalumination occurs when a substrate contains an olefinic bond in a side chain.

■ Reactions of Hydrazidoyl Halides with Sulfer Compounds

Ahmad Sami Shawali

*Department of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt