HETEROCYCLES

■ To the Memory of Professor Doctor Hans Schmid

M. Viscontini*

*,

■ Preparation and Analgesic Activity of Some 3,4-Disubstituted N-Methylmorphinans of the (-)-Series

Mohamad F. Rahman and Arnold Brossi*

*Laboratory of Chemistry, Metabolism and Digestive Diseases, National Institute of Arthritis, Bethesda, Marylanf 20014, U.S.A.

Abstract

Some reactions of (-)-3-methoxy-4-hydroxy-N-methylmorphinan (2) obtained from dihydrothebainone (1) were investigated. The analgesic properties of compounds 2, 3, 4, 5 and 6 compared to morphine hydrochloride and levorphenol are reported.

■ A Novel Method for Acetylization of Formyl Group at the C₃-Position of 2,3-Dihydro-1H-pyrrolo[1,2-a]indole Skeleton

Tetsuji Kametani,* Yoshio Kigawa, Kimio Takahashi, Hideo Nemoto, and Keiichiro Fukumoto

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

Abstract

Reaction of 2,3-dihydro-7-methoxy-6-methyl-1H-pyrrolo[1,2-a]indole-9-carboxaldehydes 2, 3, 4, 5, and 6 with thiolacetic acid in the presence of 6N sulfuric acid at room temperature gave 2,3-dihydro-7-methoxy-6-methyl-9-dithiolacetylmethyl-1H-pyrrolo[1, 2-a]indoles 12, 13, 14, 15, and 16, respectively. The same reaction of the compound 2 at 0 ° afforded 1-acetoxy-2,3-dihydro-7-methoxy-6-methyl-8-nitro-9-dithiolacetylmethyl-1H-pyrrolo[1,2-a]indole (11). Successive treatment of the compound 11 with anhydrous methanol in the presence of sodium methoxide gave 2,3-dihydro-1-hydroxy-7-methoxy-9-dimethoxymethyl-6-methyl-8-nitro-18-pyrrolo[1,2-a]indole (17).

■ Photo-oxygenation of Berberine. A Novel Conversion of Berberine to (±)-Ophiocarpine, (±)-α- and (±)-β-Hydrastine

Miyoji Hanaoka,* Chisato Mukai, and Yoshio Arata

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

Abstract

Photo-oxygenation of berberinium chloride (I) afforded 8-methoxyberberinephenolbetaine (III), which had been already converted to (±)-α- and (±)-β-hydrastine(IV and V). Sodium borohydride reduction of III yielded (±)-ophiocarpine(IX) and (±)-13-epi-ophiocarpine (X).

■ Anodic Dimerization of 1,2,3,4-Tetrahydrocarbazole

James M. Bobbitt* and John P. Willis

*Department of Chemistry, The University of Conneticut, Storrs, Conneticut 06268, U.S.A.

Abstract

The oxidation of 1,2,3,4-tetrahydrocarbazole (1) in CH₃CN-H₂O (9 : l) containing LiC10₄ (0.1N) at a graphite anode, in a two-compartment cell, and at +0.7 V (vs. SCE) gives a dehydro-dimer in 60-90% yield. The dimer has been identified as the 1,9’ dimer (2).

■ Studies on the Synthesis of Bisindole Alkaloids. XI. Novel Isomers of Vinblastine

James P. Kutney* and Brian R. Worth

*Department of Chemisry, University of British Columbia, Vancouver 8, V5T 1W5, Canada

Abstract

Polonovski-type coupling between 3β-acetoxydihydrocatharanthine N-oxide and vindoline provided 3’α-acetoxy-4’-deoxyvinblastine (VII) and 3’α-acetoxy-4’-deoxyleurosidine (VI). Hydroboration/oxidation and subsequent acetylation of 3’,4’-dehydrovinblastine (VIII) gave a further isomer, 3-O-acetyl-3’β-acetoxy-4’-deoxyvinblastine (XI).

■ Dynamic Conformationaland Exchange Processes in 2-(4’-Pyridyl)benzazoles

Claude Marzin,* Michael E. Peek, José Elguero, Hubert P. Figeys, and Nicole Defay

*Université des Sciences et Techinique du Languedoc, Plave E. Bataillon, 34060 Montpellier Cedex, France

Abstract

The barrier to the rotation about the C-C bond linking the two heterocycles of 2-(4’-pyridyl)benzazoles and of their pyridinium salts is too low to be measured by proton nmr spectroscopy at 60 MHz. A slowing down of the proton exchange between the two benzimidazole nitrogen atoms has been shown to occur. The conformation of the different molecules is discussed.

■ The Synthesis of Some 3-Nitroso-2-arylimidazo[1,2-a]pyrimidies

Derek T. Hurst* and John A. Saldanha

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

Abstract

The reaction of 2-arylimidazo(1,2-a)pyrimidines in glacial acetic acid with aqueous sodium nitrite at room temperature has been shown to give good yields of the 3-nitroso-2-arylimidazo(1,2-a)pyrimidines. Reduction of these products leads to the 3-amino derivatives.

■ The Reaction of N₄S₄ with Phenylacetylene and Methyl Propiolate

Masashi Tashiro,* Shuntaro Mataka, and Kazufumi Takahashi

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

Abstract

The reaction of N₄S₄ with phenylacetylene (1d) and methyl propiolate (1e) was investigated. The reaction with 1d gave 3-phenyl- (2d), 3-amino-4-phenyl-1,2,5-thiadiazole (4d) and [1,2,5-thiadiazolo]dithiatriazapentalene (5) in 15, 5 and 8% yields respectively. The reaction with afforded the corresponding 1,2,5-thiadiazoles, 2e and 3e in 7 and 5% yields respectively, together with a small amount of trithiadiazepine (6) and the adduct (7) of the fragment arising from the cleavage of the C≡C bond of 1e with N₃S₃.

■ Novel Synthesis of Heterocyclic Compounds from Thioacyl Chlorides

Kitaro Oka* and Shoji Hara

*School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan

Abstract

The first application of the thioacyl chlorides to the synthesis of heterocyclic compounds such as quinoxaline, 2-thiazoline, benzoxazole and benzimidazole is described.

■ A Simple Synthesis of 3-Aryl-1,5,7-trimethylpyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-diones

Keitaro Senga,* Junko Sato, and Sadao Nishigaki

*Pharmaceutical Institute, School of Medicine, Keio University, Shinanomachi 35, Shinjuku, Tokyo 160-0016, Japan

Abstract

Treatment of 6-(benzylidene-1’-methylhydrazino)-1,3-dimethyluracils with thionyl chloride afforded the corresponding 3-arylpyrazolo[3,4-d]pyrimidines.

■ Synthesis of s-Triazolo[1,5-b]isoquinolines. New Stable o-Quinonoid Heterocycles

Yasumitsu Tamura,* Midori Iwasaki, Yasuyoshi Miki, and Masazumi Ikeda

*Faculty of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Toyonaka, Osaka 560-0043, Japan

Abstract

The synthesis and some properties of new stable o-quinonoid heterocycles, s-triazolo[l,5-b]isoquinolines, are described.

■ Concentration Dependent Photoxidation of 13-Hydroxyberberinium Phenolbetaine and Formation of Stable Epidioxy Compound

Yoshikazu Kondo,* Hideo Inoue, and Jiro Imai

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

Abstract

Irradiation of an oxygenated solution of 13-hydroxyberberinium phenolbetaine 2 in over 0.1% concentrations gave a stable epidioxy derivative, 8,13a-epidioxy-2,3-methylenedioxy-9,10-dimethoxy-13-oxodibenzo[a,g]quinolizidine 4 in 42% yield. Contrast to it, in a below 0.01% solution photoxidation of 2 gave berberal 5 in 56% yield.
The reactions are interpreted as occurring by initial addition of singlet oxygen to give a peroxide intermediate A which subsequently gave 4 and 5 via the 1,2-dioxetane B depending upon concentrations of A, respectively.

■ A Simple Conversion of Norcoralyne into Phthalideisoquinoline

Jiro Imai and Yoshikazu Kondo*

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

Abstract

A new simple conversion of the berberine type alkaloid into the phthalideisoquinoline alkaloid was described by a sequence involving intramolecular rearrangement of the 8,13a-epidioxy intermediate B via the three-membered cyclic peroxide D, to 2’-carboxypapaveraldine which was reduced with NaBH₄ to give the phthalideisoquinoline 5.

■ A New Class of Purines. Synthesis of 3,9-Dialkylhypoxanthines by the Cyclization of 1-Alkyl-5-alkylaminoimidazole-4-carboxamides

Taisuke Itaya* and Kazuo Ogawa

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

Abstract

Alkylation of N,N-diethyladenine (I) with alkyl halides in the presence of potassium carbonate gave mainly N,N-diethyl-9-alkyladenines (II), which were converted to 1-alkyl-5-alkylaminoimidaaole-4-carboxamides (IV) via N,N-diethyl-3,9-dialkyladeninium salts (III). Heating IV in a mixture of triethyl orthoformate and acetic anhydride produced hitherto unknown 3,9-dialkylhypoxanthines (V) as well as N-diethoxymethyl-1-alkyl-5-(N-alkylformamido)imidazole-4-carboxamides (VI).

■ Chiral Oxazolines in Asymmetric Synthesis. Effect of Substituents on Asymmetric Induction

A. I. Meyers,* Arthur Mazzu, and Charles E. Whitten

*Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, U.S.A.

Abstract

Variation in the 5-substituent on chiral oxazolines leads to large variations in the degree of asymmetric alkylations. These results indicate that both steric and chelating effects are important in achieving high enantiomeric excesses in the product.

■ 4H-Pyrazolo[1,5-a]benzimidazole

Misbahul Ain Khan* and Vera Lucia Teixeira Ribeiro

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

Abstract

The parent ring system pyrazolo[l,5-a]benzimidazole has been obtained from the decarboxylatian of the acid received in the hydrolysis of ethyl 4H-pyrazolo[l,5-a]benzimidazole-3-carboxylate.

■ Synthesis of 1H-Pyrano[2,3-c]pyrazole-4-ones

Misbahul Ain Khan,* Mario Celso Pagotto, and Gwynn Pennant Ellis*

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

Abstract

Various derivatives of the ring system-1H-pyrano[2,3-c]pyrazole-4-one have been obtained by the condensation of 4-acetyl-3-methyl-1-phenylpyrazol-5-one appropriate esters followed by cyclization with acids. Further reactions gave other derivatives of 1H-pyrano[2,3-c]pyrazole-4-one.

■ A Review on the Syntheses of the 9-Substituted Acridines (1970-1976)

Stanislaw Skonieczny*

*Laboratory of Chemistry and Biochemistry of Antitumour Compound, Institute of Organic and Food Chemistry and Technology, Techinical University of Gdansk, 80-952 Gdansk 6, Poland

Abstract

A summary of synthetic works published in the 1970s is presented. Apart from the syntheses, mechanisms of the key steps in these reactions are included as well as spectral studies and biological properties of these newly obtained compounds are mentioned.