HETEROCYCLES

■ Synthesis and Reactivity of Heterocyclic α-Diazo Carbonyl Compounds

Axel Schmitz, Udo Kraatz, and Friedhelm Korte*

*Institut für Organische Chemie, Technische Universität München, Lichtenbergstrasse 4, D-85747 Garching, Germany

Abstract

Synthesis of α-diazo substituted 3-carboxylic esters of isoxazolone and pyrazolone (3a,b) by diazo group transfer succeeds only with the use of the azidinium salt 2.
The thermodynamically quite stable diazo compounds 3a, b are very resistant to mineral acids but can be readily coupled to form azo derivatives with compounds containing an active C-H bond. Hydrolysis of their labile phosphazines 6a, and b readily gives the hydrazones 7a,b.

■ Synthesis of A-Thienosteroids and Related Compounds

Taichiro Komeno,* Hikozo Iwakura, and Ken’ichi Takeda

*Shionogi Research Laboratories, Shionogi & Co. Ltd., Fukushima-ku, Osaka 553-0002, Japan

Abstract

The Grignard reaction of optically active 1,5-dioxo-7α-methyl-3aα,7aβ-hexahydroindan-4α-yl acetic acid with 2- and 3-thienyl magnesium bromide, followed by lactonization gave thienyl γ-lactones, 8a and 8b, respectively. Their configurations were established by the dipole moments. They were converted through multi-steps to a number of A-thienosteroids, namely modified steroids in which the ring A are displaced by fused thiophenes. A-thiolenone derivatives also were prepared from these A-thienosteroids.

■ Nucleophilic Reactions of 5,6-Dihydronicotinic Acid Esters and a Novel Method for the Preparation of 1,4,5,6-Tetrahydropyridine-3-carboxylic Acid Esters

Ulrich Renner*

*Pharmaceuticals Division, Research Department, Ciba-Geigy Limited, CH-4002 Basel, Switzerland

Abstract

Reaction of 1,5-diaminopentan-3-one V with ethyl acetoacetate yielded diazaspiro-undecadiene-dicarboxylic acid ester VI by a one-step synthesis. Novel 4-aroyl- 1,4,5,6-tetrahydropyridine-3-carboxylic acid esters XI and condensed analogs XI11 have been prepared by cycloaddition of ethyl acetoacetate to α-methylene-6-aminopropiophenones or their cyclized analogs respectively.

■ Structure Dependent Reactivity in the Oxygenation of Thiane Analogs by a Cytochrome P-450 Recon-stituted Enzyme System

Tadashi Takahashi, Y. H. Kim, Daikichi Fukushima, Ken Fujimori, Shigeru Oae,* and Takashi Iyanagi

*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki, 305-8571, Japan

Abstract

Thiane analogs were oxidized to the corresponding sulfoxides by the reconstituted system of purified rabbit liver microsomal cytochrome P-450 — NADPH-cytochrome P-450 reductase. The stereochemical results and kinetic behaviors were discussed in comparison with those of the nonenzymatic oxidations of the thiane analogs by NaIO₄. The enzymatic oxygenation of thianes was found to be nonstereospecific, however, the rates of the enzymatic oxygenation was found to be effected by the hydrophobicity of the substrate.

■ Synthesis of B-Homoaporphine Skeleton. Steric Requirements in the Formation of the Phenanthro[10,1-b,c]azepine System

Ichiya Ninomiya* and Takeaki Naito

*Kobe Women’s College of Pharmacy, Motoyamakita, Higashinad, Kobe, Hyogo 658, Japan

Abstract

B-Homoaporphine skeletons (4a and b) were prepared via two routes; the photocyclization of the 1-phenyloxazolo[4,3-a][2]benzazepin-3-one (1) and the Friedel-Crafts-type cyclization of 2-oxophenanthro[9,10-d]oxazoline-3-propionic acid (6c).

■ Synthesis of Imidazo[4,5-b]pyridines

Isao Hayakawa,* Ken-ichi Yamazaki, Renzo Dohmori, and Naofumi Koga

*Exploratory Research Laboratories I, Daiichi Pharmaceutical Co., Ltd., 16-13, Kitakasai 1-chome, Edsogawa-ku, Tokyo 134, Japan

Abstract

Novel syntheses of an imidazo[4,5-b]pyridine and its alkyl derivatives were studied and the structures of the products were determined.

■ Synthesis of Tritium and of Deuterium Labelled Pteridines of High Activity

Heinz Rembold* and Günter Hennings

*Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Gottingen, Germany

Abstract

2,4-Diamino-6,7-dimethylpteridine and 2-amino-4-hydroxy-6,7-dimethylpteridine were synthetized with high specific ³H and ²D labelling in the 6,7- and the 7-methyl groups. The isotopes are stable in these positions. No HT- or HD-exchange could be observed.

■ The Primary Structure of the Monomeric Hemoglobin (Erythrocruorin)Component CTT-of Chironomus thummi thummi (Insecta, Diptera)

Traute Kleinschmidt, Helgan yon der Mark-Neuwirth and Gerhard Braunitzer*

*Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Gottingen, Germany

Abstract

The amino acid sequence of the monomeric component CTT-I, one of 12 of the hemoglobins (Erythrocruorins) of larvae of Chironomus thummi thummi (Insecta, Diptera) is given. The sequence and the side chains forming the heme complex are discussed.

■ Annelation by Intramolecular 1,3-Dipolar Addition of Nitrones

Takenori Kusumi, Satoru Takahashi, Yoko Sato, and Hiroshi Kakisawa*

*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki, 305-8571, Japan

Abstract

Intramolecular 1,3-dipolar cyclization of the nitrone 2 gave the perhydroindane 5 as a regio and stereoselective product.

■ Reaction of β-Aminocrotonamides with α-Haloketones and α-Hydroxyketones

Tetsuzo Kato,* Takuo Chiba, Masaki Noda, and Makoto Sasaki

*Pharmaceutical Institute, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan

Abstract

Reaction of bromoacetophenone (4) with β-aminocrotonamide (1) and β-aminocrotonanilide (2) gave 2-methyl-5-phenylpyrrole-3-carboxamide (6) and 2-methyl-5-phenylpyrrole-3-carboxanilide (7), respectively. Similarly, 2-chlorocyclohexanone (5) reacted with (1), (2) and β-amino-(N-methyl)crotonamide (3) to give 2-methyl-4,5,6,7-tetrahydroindole-3-carboxamide derivatives (8, 9 and 10).
Reactions of α-hydroxyketones such as benzoin (11) and acetoin (12) with (1), (2) and (3) afforded 2-methylpyrrole-3-carboxamide derivatives (13 - 18).

■ Synthesis of Multicyclic Keto Lactams by the Photo-ring-expansion of N-(1-Adamantyl)succinimides

Masanao Terashima, Kazue Ohkura, Haruo Okajima and Yuichi Kanaoka*

*Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan

Abstract

Upon irradiation N-(1-adamantyl)succinimides with carbocyclic substituents on the imide ring undergo the ring-expansion reaction in fairly good yields affording various multicyclic keto lactam systems.

■ Reactivity of Imidazo [1,2-b]pyridazine 1-Oxides

Kazue Satoh and Tadashi Miyasaka*

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

Abstract

The treatment of either imidazo[1,2-b]pyridazines (III) or their 1-oxides (III) with excess organic peracid resulted in the oxidative cleavage of imidazole moiety to give 3-(N-acylhydroxylamino)pyridazines (IV). The bromination and nitration of II gave the corresponding 3-substituted N-oxides (VII, IX, X, and XI). Rearrangement reaction of II with phosphoryl chloride or acetic anhydride afforded the deoxygenated 7-substituted imidazopyridazines, XII and XIII, respectively.

■ Pathophysiologische Bedeutung von L-Carnosin auf die Wundheilung

Kineshiro Nagai* and Toshio Yamane

*School of Dentistry at Niigata, The Nippon Dental University, Hamaura-cho 1-8, Niigata 951, Japan

■ Annelation Reaction by Using Heterocyclic Compounds

Tetsuji Kametani* and Hideo Nemoto

*Pharmaceutical Institute, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan

Abstract

This review deals with the recent advances in the use of heterocvclic compounds as annelating reagents, especially as applied to the synthesis of natural products.

■ Synthesis and Cytokinin-Agonistic and Antagonistic Activities of Substituted Pyrrolo[2,3-d]pyrimidines: Development of Anticytokinins

Hajime Iwamura*

*Kyoto University, Yoshida, Sakyou-ku, Kyoto 606-8501, Japan

Abstract

Recent studies of cytokinin antagonists were reviewed, with special attention on substituted pyrrolo[2,3-d]pyrimidines. Principles for the design of anticytokinin-active compounds, their specific antagonistic nature, agonist-antagonist descrimination and chemical structure/activity relationship in terms of steric bulk of side chain and the utilization of anticytokinins in studies of plant growth are the major objects discussed.

■ Carbon-13 Nuclear Magnetic Resonance Studies of Colletotrichins and Their Biosynthesis

Yasuo Kimura,* Masatoshi Gohbara, Akinori Suzuki, and Saburo Tamura

*Department of Agricultural Chemistry, Faculty of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan

Abstract

The ¹³C-nmr spectra of three related secondary fungal metabolites, colletotrichin (I), colletotrichin B (II), and C (III), isolated from Colletotrichum nicotianae have been studied. Labelling patterns of these compounds derived from 13c-formate, 1-¹³C-, 2-¹³C-, and 1,2-¹³C-acetates, and 5-¹³C-mevalonate have been determined. These compounds were proved to be biosynthesized in combination of acetate-mevalonate-geranyl-geranyl pyrophosphate route with acetate-polyketide route. Moreover, a new pathway, which involves cyclization of geranyl geranyl pyrophosphate into I, II, and III was proposed.

■ Piericidins: Naturally Occurring Inhibitors against Mitochondrial Respiration

Shigeo Yoshida* and Nobutaka Takahashi

*Department of Agricultural Chemistry, Faculty of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan

■ Total Syntheses of Natural Products from Five-membered Heterocyclic Compounds as Starting Materials

Tetsuji Kametani* and Keiichiro Fukumoto

*Pharmaceutical Institute, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan

Abstract

Total syntheses of natural products, in which the carbon-unit generated by ring opening of five-membered heterocyclic compounds is either a starting material or a key intermediate, are described.

■ Syntheses of 5,10b-Ethanophenanthridine and Related Alkaloids Occurring in Amaryllidaceae

Yoshisuke Tsuda*

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

Abstract

Synthetic works on the titled compounds including the following articles are reviewed.