HETEROCYCLES

■ Morphinans and 6-Ketomorphinans Unsubstituted in the Aromatic Ring.High Analgesic Activity of (—)-6-Keto-N -methylmorphinan, IV

Helmut Schmidhammer, Arthur E. Jacobson, and Arnold Brossi*

*Medical Chemistry Section, Laboratory of Chemistry, NIDDK, National Institute of Health, Bethesda, MD 20892, U.S.A.

Abstract

Elimination of the phenolic hydroxy group from (-)-4-hydroxy-6-kero-N-methylmorphinan (1) afforded the morphinan ketone 3 which was several times more potent as an analgesic than morphine. Removal of the carbonyl group in 3 by a Wolff-Kishner reduction gave the unsubstituted morphinan 7 which was only half as potent as morphine.

■ Photochemistry of 6-Chloro-2-pyridones: The First Example for Electrocyclic Ring Opening of the Pyridone Ring System

Chikara Kaneko,* Harue Fujii, and Keiko Kato

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

Abstract

Irradiation of 6-chloro-2-pyridone in methanol gave two geometrical isomers (cis and trans) of methyl 4-cyano-3-butenoate and trans isomer of methyl 4-cyano-2-butenoate: this and the related reactions provide the first example for the photochemical electrocyclic ring opening of 2-pyridone ring.

■ Reactivity of 5-Methyl-2H -1,2,6-thiadiazin-3(6H )-one 1,1-Dioxide towards Alkylating Agents and Carbenes

José Elguero,* Carmen Ochoa, and Manfred Stud

*Instituto de Química Médica, C. S. I. C., Calle Juan de Cierva, 3, 28006 Madrid, Spain

Abstract

The reaction between 5-methyl-2H-1,2,6-thiadiazin-3(6H)-one 1,1-dioxide 1 and a variety of alkylating agents (diazomethane, trimethyl phosphite, dimethyl sulfate, and methyl iodide) in different conditions has been studied. Five methyl derivatives have been isolated and characterized. The reaction between 1 and carbenes proceeds with difficulty and only in the case of the carbene obtained from ethyl diazoacetate has the addition product been isolated.

■ New Synthetic Approach for Azolopurines and Analogs

Miha Tisler,* Branko Stanovnik, and Zdenka Zrimsek

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

Abstract

A new synthetic approach has been developed for the synthesis of some azolopurines, i.e. derivatives of 1,2,4-triazolo(3,4-b)purine (3) and pyrrolo(2,1-b)purine (8), and for some pyrazolo(3,4-d)pyrimidines (12, 14).

■ Activated Lactams: Reaction of Ketene-S,N -acetals with Aryl Isocyanates

Hiroki Takahata, Masaharu Nakano, Akira Tomiguchi, and Takao Yamazaki*

*Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan

Abstract

Reaction of ketene-S,N-acetals (1, 2, and 3) as activated lactams with aryl isocyanates (4a-d) has been described. The vinylogous ureas (6a-d and 7a-d) obtained by this reaction have been utilized as intermediates for the synthesis of some uracil derivatives.

■ A One Pot Synthesis of 4-Hydroxymethylindole

Masanori Somei* and Toshiya Shoda

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

Abstract

A practical one pot synthetic method of 4-hydroxymethylindole is developed. The method consists of three operations, in which a novel ring transformation reaction of isocoumarins into isochromans is included. Product analysis and distribution of each operation are also described in detail.

■ Syntheses of Spironitrogen Multicyclic Systems by Photocyclization of N -Cycloalkenylphtalimides

Minoru Machida,* Kazuaki Oda, and Yuichi Kanaoka

*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan

Abstract

Photolysis of the N-cycloalkenylphthalimide 4 (m > 1) in methanol gave spiro-nitrogen multicyclic products 5. In the case of m=1, pyrrolo[2,1-a]isoindole derivatives (6, 7) were obtained. This support a mechanism involving an electron transfer followed by the anti-Markownikoff addition of methanol.

■ Direct Fluorination of Isoquinoline Compounds

Yoshiro Kobayashi,* Itsumaro Kumadaki, and Toshinori Yamashita

*Tokyo College of Pharmacy, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan

Abstract

Activation of isoquinoline for the direct fluorination was achieved by its conversion to 2-methylisocarbostyril. The fluorination of 2-methylisocarbostyril gave 4-fluoro compound in a satisfactory yield. The Reissert’s compound was not reactive enough for the fluorination.

■ Probing Ion Channels with Natural and Synthetic Heterocycles

Bernhard Witkop*

*National Institute of Arthritis, Diabetes,and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20205, U.S.A.

Abstract

Professor Tsuda’s pioneering ccntributions to the crystallization and elucidation of tetrodotoxin serve as the starting point of a review on natural and synthetic heterocycles that have helped to study the topography, characteristics and dynamics of ion channels and membrane pores serving the influx and efflux of sodium, potassium and calcium.

■ Nicotianamine and Analogous Amino Acids, Endogenous Iron Carriers in Higher Plants

Helmut Ripperger and Klaus Schreiber*

*Institute of Plant Biochemistry, Academy of Sciences of the GDR, DDR-4020 Halle/Saale, Germany

Abstract

The occurrence, structural elucidation and synthesis of nicotianamine (1) and of the analogous amino acids mugineic acid (4), 2’-deoxymugineic acid (5), 3-hydroxymugineic acid (6) as well as of avenic acid A (7) and B (8) have been reviewed. These compounds possess chelating properties for iron and other metal ions and are considered to be specific phytosiderophores of general importance for the iron (metal) transport and/or metabolism in higher plants.

■ Synthesis of Carbapenem Antibiotics

Tetsuji Kametani,* Keiichiro Fukumoto, and Masataka Ihara

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

Abstract

A family of β-lactam antibiotics, having the 1-carbapen-2-em ring system, represented by thienamycin, possesses potent and broad antibiotic activities. In this review, total syntheses and approaches of the antibiotics are summarized according to the manner for the formation of the bicyclic ring system.

■ Syntheses of 1-Azaspiro-[5.5]undecanes: Stereoselective Syntheses of Perhydro- and Octahydrohistrionicotoxin

Yasuo Inubushi* and Toshiro Ibuka

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

Abstract

Syntheses of 1-azaspiro[5.5]undecane derivatives, which may be potential candidates for the therapeutic application and the promising precursors for the histrionicotoxins syntheses, are described. Stereoselective syntheses of racemic octahydro- and perhydrohistrionicotoxin are also presented.

■ A New Practical Synthetic Method: Monitored Aminolysis of 3-Acyl-1,3-thiazolidine-2-thione

Yoshimitsu Nagao and Eiichi Fujita*

*Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan

Abstract

This review article deals with the monitored aminolysis of 3-acyl-1,3-thiazolidine-2-thione and its applications to the total synthesis of macrocyclic spermidine alkaloids, codonocarpine, (±)-lunarine, and (±)-lunaridine, and the peptide synthesis. Biological and physiological activities of 3-acyl-1,3-thiazolidine-2-thione are briefly described.

■ The ¹³C-NMR Spectra of Polyether Antibiotics and Some Empirical Rules for Structural Studies of Polyether Antibiotics

Haruo Seto* and Noboru Otake

*Institute of Applied Microbiology, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8567, Japan

Abstract

The ¹³C-nmr spectral assignments of s subgroup of the polyether antibiotics including lonomycin, mutalomycin, carriomycin, etheromycin, A204A, septamycin, nigericin and monensin are summarized. Based on these spectral data, some empirical rules for structural elucidation of polyether antibiotics have been established and their application to a new antibiotics is presented.

■ The Total Synthesis of Macrocyclic Spermine and Spermidine Alkaloids

Harry H. Wasserman* and James S.Wu

*Department of Chemistry, Yale University, P.O. Box 6666, New Haven, Connecticut 06511, U.S.A.

Abstract

Useful new synthetic methods for the preparation of macrocyclic spermine and spermidine lactam alkaloids have recently been developed. This review describes work which has led to the total synthesis of a number of compounds in this series.

■ Studies on the Diterpene Alkaloids of the Chinese Drug, Aconitum Spp

Zhu Yuanlog (Chu Yuan-Lung) and Zhu Renhong (Chu Jen-Hung)*

*Faculty of Pharmacy, School of Medicine, Department of Organic Chemistry, Institute of Chemical Sciences, 90-145 Lodz, Narutowicza 120a, Poland

Abstract

Ten new diterpene alkaloids recently isolated from Chinese aconites are reviewed.

■ Azanucleosides and Deazanucleosides of Biological Interest

Yoshihisa Mizuo,* Tokuo Itoh, and Akihiko Nomura

*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan