HETEROCYCLES

■ Synthetic Studies on β-Lactam Antibiotics. IV. Synthesis of 1,9b-Dihydro-2H,4H-2-oxo-azeto[1,2-c][1,3]benzopxazine Derivatives

Tetsuji Kametani,* Kazuo Kigasawa, Mineharu Hiiragi, Kikuo Wakisaka, Hideo Sugi, and Keizo Tanigawa

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

Abstract

Synthesis of novel tricyclic β-lactams, 1,9b-dihydro-2H,4H-2-oxo-azeto[1,2-c][1,3]benzoxazines (14 and 15), was achieved by a cycloaddition reaction of 2-(4-chlorophenyl)-4-methylthio-2H-1,3-benzoxazine (12) with phenoxyketene followed by desulphurisation of the product (13).
This paper also describes a synthetic approach to an azeto[1,2-c][1,3]benzoxazine through reaction of an acyclic imine with ketene.

■ Synthetic Studies on β-Lactam Antibiotics. VI. Synthesis of 7H-azeto[1,2-a]thieno[2,3-c]pyridine Derivatives

Tetsuji Kametani,* Keiichiro Fukumoto, Kazuo Kigasawa, Mineharu Hiiragi, Kikuo Wakisaka, Keiso Tanigawa, and Hideo Sugi

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

Abstract

Methyl 4,5-dihydrothieno[2,3-c]pyridine-5-carboxylate (4) was converted into several 8-substituted 4,5,8,8a-tetrahydro-7-oxo-7H-azeto[1,2-a]thieno[2,3-c]pyridine-7-carboxylates (7 ~ 10) by reaction with phthalimidoacetyl chloride and triethylamine, followed by hydrolysis and acylation.

■ 3,6-Bis-substituted s-Tetrazines

William D. Guither, Michael D. Coburn, and Raymond N. Castle*

*Department of Chemistry, Brigham Young University, Provo, UT 84602, U.S.A.

Abstract

The preparation of various substituted s-tetrazines is described.

■ Rapid Base Induced Rearrangement of Some Quaterinized Thiazoles to Thietanes

Hans-Jürgen Federsel,* Jan Bergman, and Urban Stenhede

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

Abstract

The synthesis of various thietanylidene compounds through sodium hydroxide treatment of some quaternized 5-(β-chloroethyl)-4-methylthiazoles is described and discussed.

■ The Use of Quinizarin Diboroacetate as a Dipolarophile in the Synthesis of Fused Tertacyclic Isoxazoles and Pyrazoles

Alan M. Birch, Anthony J. H. Mercer,* and Colin W. Greenhalgh

*School of Analytical and Biological Chemistry, Kingston Polytechnic, Kingston-on-Thames, KT1 2EE, U.K.

Abstract

Quinizarin diboroacetate undergoes [3 + 2] cycloaddition reactions with benzonitrile oxide to give an anthra[2,3-d]isoxazole (2) and with diphenyldiazomethane to form an anthra[2,3-c]pyrazole (4) which decomposes at 250° to a 13H-indenoanthracene (8); the diphenyldiazomethane dihydroadduct (9; R=B(OAc)₂) undergoes thermal decomposition at room temperature to give 2-(diphenylmethyl)quinizarin (11).

■ A Photo-rearrangement of 5-Diazouracil. A Convenient Systhesis of 2-Oxo-4-imidazoline-4-carboxylic Acid Derivatives

Branko Stanovnik,* Miha Tisler, and Ernest Voncina

*Department of Chemistry, University of Ljubljana, 61000 Ljubljana, Slovakia

Abstract

A photochemical transformation of 5-diazouracil alcohol adducts into 2-oxo-4-imidazoline-4-carboxylates under strongly acidic conditions is described.

■ An Alternative Synthesis of the Emetine Alkaloids from (±)-Norcamphor Intending for a Chiral Synthesis. A Synthesis of (±)-Protoemetinol and (±)-Protoementine and a Formal Synthesis of (±)-Emetine

Seiichi Takano,* Yoko Takahashi, Susumi Hatakeyama, and Kunio Ogasawara

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

Abstract

Intending for using (-)-norcamphor as a chiral precursor, (±)-norcamphor (1) has been converted into (±)-protoemetinol (7), (±)-protoemetine (20) and the emetine precursor (5) stereoselectively through a novel epimerization reaction.

■ Thermolysis of Oxime O-Allyl Ethers: A New Method for Synthesis of Pyridine Derivatives

Hiroshi Irie,* Itsuko Katayama, Yukio Mizuno, Junko Koyama, and Yukio Suzuta

*Faculty of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-machi, Sakyo-ku, Kyoto 606-8501, Japan

Abstract

A new method for constructing pyridine ring by thermolysis of oxime O-allyl ethers of several ketones in the presence of oxygen is described.

■ The Reaction of 2,4,6-Triarylpyrylium Cations with Methoxide-Ion

Alan R. Katritzky,* Robert T. C. Brownlee, and Giuseppe Musumarra

*School of Chemical Sciences, University of East Anglia, Norwich, Northfolk NR4 7TJ, U.K.

Abstract

The title reaction is shown by ¹³C nmr to give 2-methoxy[2H]pyrans: no evidence was found for 4-adducts or ring opened compounds.

■ Alkaloids of Delphinium virescens Nutt.: Virescenine and 14-Acetylvirescenine

S. William Pelletier,* Naresh V. Mody, Atanas P. Venkov, and Samuel B. Jones, Jr.

*Department of Chemistry, Institute for Natural Products Research, The University of Georgia, Chemistry Building, Athens, Georgia 30602-2556, U.S.A.

Abstract

Investigation of Delphinium virescens Nutt. has led to the isolation and structure elucidation of two new lycoctonine-type alkaloids, virescenine (1) and 14-acetylvirescenine (2), as well as the known alkaloids, browniine (3) and ajaconine (4).

■ Structure of Ephedradine B, a Hypotensive Pronciple of Ephedra Roots

Mitsuru Tamada, Katsuya Endo, and Hiroshi Hikino*

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

Abstract

From the crude drug “mao-kon”, the roots of Ephedra plants, a novel macrocyclic spermine alkaloid ephedradine B showing the hypotensive activity has been isolated whose stereostructure has been elucidated as represented by formula I on the basis of chemical and physical evidence.

■ Addition Reactions of Indolizine Derivatives with Diethyl Azodicarboxylate

Mituo Masumura* and Yoshiro Yamashita

*Department of Applied Chemistry, Faculty of Engineering, University of Tokushima, Minamijosanjima-cho, Tokushima 770-8506, Japan

Abstract

Indolizines reacted with diethyl azodicarboxylate (DAD) to give Michael type adducts 2. These adducts 2 underwent novel addition reactions with DAD to give 1:2 adducts 3. These addition reactions are useful methods for synthesis of indolizine derivatives.

■ A Simple and Facile Total Synthesis of Sesquiterpene, Cuparene by Using Furan Derivatives

Tetsuji Kametani,* Masayoshi Tsubuki, and Hideo Nemoto

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

Abstract

5-Methyl-2-(4-methylbenzyl)furan (4) obtained from the condensation of 2-lithio-5-methylfuran with 4-methylbenzyl bromide was converted into 3-methyl-2-(4-methylbenzyl) cyclopenten-2-one (6) via 1-(4-methylphenyl)-hexane-2,5-dione (5). 1,4-Addition of methyl group into 6 furnished 3,3-dimethyl-2-(4-methylphenyl)cyclopentanone (7). This result constitutes a formal total synthesis of cuparene (9).

■ Synthetic Studies on β-Lactam Antibiotics. V. Stereoselective Synthesis of 1,9b-Dihydro-2H,4H-2-oxo-azeto[1,2-c][1,3]benzoxazine-4-carboxylic Acid Derivatives

Tetsuji Kametani,* Kazuo Kigasawa, Mineharu Hiiragi, Kikuo Wakisaka, Hideo Sugi, and Keizo Tanigawa

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

Abstract

2,2,2-Trichloroethyl 1-phthalimido-1,9b-dihydro-2H,4H-2-oxo-azeto[1,2-c][1,3]benzoxazine-4-carboxylate (11) was synthesised stereoselectively by cyclisation of 2,2,2-trichloroethyl 2-[cis-4-(2-hydroxyphenyl)-3-phthalimido-2-oxo-1-azetidinyl]2-hydroxyacetate (8), which was prepared from N-(2-benzyloxybenzylidene)-2,4-dimethoxybenzylamine (4) by cycloaddition with ketene, followed by debenzylation and condensation with 2,2,2-trichloroethyl glyoxalate. The corresponding p-nitrobenzyl ester (12) which was obtained by a similar method, was converted to the free carboxylic acid (16).

■ Drug Interactions of Cephalosporin Derivatives with Gabexate Mesilate

Katsuo Unno, Toshio Suzuki, Kyusei Ataku, Hisae Nakata, Akiko Tomino, and Tetsuji Kametani*

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

Abstract

A mixture of sodium cephalotin (1), sodium ceftezole (2), sodium cefazoline (3), sodium cefapirin (4), and sodium cefacetrile (5) with gabexate mesilate (FOY) (6) in water produced the salts (7), (8), (9), (10) and (11), respectively, as precipitates, which were examined for antibacterial activity against various strains.

■ The “One Pot” Photochemical Synthesis of 2-Methyl-3-carboethoxy-5-phenylindole

René Beugelmans,* Hélène Ginsburg, Marie-Thérèse Le Goff, Alexandra Lecas, Jacques Pusset, and Georges Roussi

*Institut des Chimie des Substances Naturelles, C.N.R.S., 1 avenue de la Terrasse, Bat. 27, 91198 Gif-sur-Yvette Cedex, France

Abstract

The title compound 6 is obtained by UV irradiation of 4-nitro-biphenyl in the presence of diethyl malonate anion. The very complex course of the process, involving reactions (a, b, c, d, e) is discussed and a sequence of intermediates 2, 3, 4, 5 is proposed.
a) Intermolecular nitro group reduction with ethyl malonate incorporation (hν) ; b) dehydration ; c) decarboxylation ; d) cyclization ; e) deoxygenation.

■ Heterocycles from Chlorosulfonyl Isocyanate I. Reaction with 2-Aminoazines

Sandor Karady, Joseph S. Amato, Daniel Dortmund, Arthur A. Patchett, Robert A. Raemer, Roger J. Tull, and Leonard M. Weinstock*

*Division of Merec and Co., Inc, Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065, U.S.A.

Abstract

The reaction of chlorosulfonyl isocyanate (CSI) with 2-aminopyridine affords thiatriazine 3. The reaction of this heterocycle with water, morpholine as well as alkylating agents is the subject of this publication.

■ Reactions of Nitrones with Ketenes

Magid A. Abou-Gharbia and Madeleine M. Joullié*

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

Abstract

A survey of the reactions of nitrones with ketenes is presented. Possible mechanisms for the reported reactions are discussed.

■ Reactions of Aromatic Heterocycles Involving the Catalytic Action of the Cyanide Ion

Eisaku Hayashi* and Takeo Higashino

*Shizuoka College of Pharmacy, 2-2-1, Oshika, Shizuoka-shi, 442 Shizuoka, Japan

■ Pyrroloquinolines V. 1H-Pyrrolo[3,2-c]quinolines

Misbahul Ain Khan* and João Ferreira da Rocha

*Seção de Quimica, Instituto Militar de Engenharia, Urca, 20.000 Rio de Janeiro, RJ, Brazil

Abstract

This review deals with the known chemistry of pyrrolo[3,2-c]quinolines including their syntheses and spectra.