HETEROCYCLES

■ Sensitized Photooxygenation of Melatonin and Related Compounds

Masako Nakagawa,* Jun Chiba, and Tohru Hino

*Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan

Abstract

Photosensitized oxygenation of melatonin (1a) and 1b at 0 °C has been found to give the corresponding 6, whereas low temperature oxygenation of 1 provided exclusively 3 which rearranged to 6 at room temperature.

■ Reactions and Syntheses with Organometallic Compounds. IX. The Total Synthesis of Iso-6-hydroxy-2’-(2-methylproyl)-3,3’-spiro-tetrahydropyrrolidino-oxindole via Arylnickel Complex

Miwako Mori and Yoshio Ban*

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

Abstract

The total synthesis of the epimeric isomer of the natural alkaloid (4b) was achieved by use of the oxindole synthesis via arylnickel complex which was prepared from Ni(PPh₃)_n and an aryl halide having the internal double bond.

■ Synthesis and Reaction of 2-Bis(methylthio)methylenecoumarin-3-ones

Yoshinori Tominaga, Keiji Kurata, Hiroshi Awaya, Yoshiro Matsuda, and Goro Kobayashi*

*Faculty of Pharmaceutical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan

Abstract

6-Methoxy-2-bis(methylthio)methylenecoumaran-3-one, which was prepared by the reaction of 6-hydroxycoumaran-3-one with carbon disulfide and subsequent alkylation with dimethyl sulfate in the presence of sodium hydroxide in dimethyl sulfoxide, reacted with nucleophiles to give the corresponding substitution products of one methylthio group in good yield.

■ Mass Spectra of Substituted 4-Cyano-1,4-dihydropyridines

Eddy Esmans,* Jan Vanbroeckhoven, Josef Lepoivre, and Frank Alderweireldt

*Labratory of Organic Chemistry, University of Antwerp (RUCA), Groenenborgerlaan 171, B-2020 Antwerp, Belgium

Abstract

The mass spectra of some 3-substituted (acetyl-; carbamoyl-) N-methyl- and N-benzyl-4-cyano-1,4-dihydropyridines were examined. Unexpected thermolysis occurs prior to ionisation and gives rise to 3-substituted N-methyl- and N-benzyl-1,4-dihydropyridine peaks in the mass spectra of these 4-cyano adducts. High resolution mass measurements were used to substantiate this hypothesis. The corresponding N-methyl- and N-benzyl-1,4-dihydropyridines were synthesised and were used as reference compounds.

■ Mechanism of Epoxidation in the Synthesis of Flavipucine. The Exchange Reaction of Its Precursors

Narindar N. Girorta* and Norman L. Wendler

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

Abstract

An elimination-addition pathway has been established for the mechanism of the epoxidation reaction leading to flavipucine as well as the exchange reactions in general of its precursors.

■ Reactions of α-Ketosulfenes with 1-Azirines

Otohiko Tsuge* and Michihiko Noguchi

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

Abstract

The reactions of benzoylsulfene 1 and two cyclic α-ketosulfenes 2 and 3, generated in situ from the corresponding sulfonyl chlorides and triethylamine, with 3-substituted 2-phenyl-1-azirines (4a-4c) proceeded through a concerted [Π4s + Π2s] process. However, 2-phenyl-1-azirine (4d) showed a different behavior toward 2 and 3 from 4a-4c.

■ Alternative Syntheses of 2,3-Benzazocin-5-one Derivatives via Pyrrolo[1,2-a]indoles

Tetsuji Kametani,* Kimio Takahashi, Masataka Ihara, and Keiichiro Fukumoto

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

Abstract

Transformations of 2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole (4) into hexahydro-2,3-benzazocine derivatives (6 and 7) using ethyl chloroformate or acetic anhydride were described.

■ Reaction of Pyrrolo[1,2-a]indole-5,8-dione Derivatives with N-Bromosuccinimide in Protic Solvents

Tetsuji Kametani,* Kimio Yakahashi, Masataka Ihara, and Keiichiro Fukumoto

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

Abstract

Treatment of the pyrrolo[1,2-a]indole-5,8-diones (1 - 5) with N-bromosuccinimide in protic solvents such as methanol and acetic acid yielded the adducts (6 - 10 and 12 - 13) in good yield. Debromination of the adduct 7 with tri-n-butyltin hydride to give 11 was also described.

■ Synthesis of Peptide Alkaloid, Amphibine-I and Related Compounds

Juno Koyama, Yukio Suzuta, Kaoru Kuriyama, Haruaki Yajima, Kaname Koyama, and Hiroshi Irie*

*Faculty of Pharmaceutical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan

Abstract

Synthesis of amphibine-I (I_A-a) and its diastereoisomeric compounds (I_A-b), (I_B-a), and (I_B-b) was completed by condensation of four diastereoisomeric 1-(α-aminoethyl)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinolines (V_A-a,b and V_B-a,b) with benzyloxycarbonyl-L-valylglycine followed by removal of the protecting group.

■ Utilization of Protopine and Related Alkaloids. X. Photochemistry of 7,8-Dimethoxy-2-methyl-3-(4’,5’-methylenedioxy-2’-vinylphenyl)isocarbostyril

Masayuki Onda* and Hiroko Yamaguchi

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

Abstract

Photolysis of the isocarbostyril (5) predominantly gives the regioisomeric dimers (7) and (8). Attempts to trap the initial photo-product with the dienophiles (9) and (17) are examined and formation pathways of the resulted products are briefly commented.

■ The Regioselectivity of the Cycloadditions of Ketenes with N-Alkyl- and N-Arylnitrones

Magid A. Abou-Gharbia, Madeline M. Joullie,* and Iwao Miura

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

Abstract

Cyclopentamethyleneketene, tert-butylcarbethoxyketene, and tert-butylcyanoketene react with N-arylnitrones to form oxazolidinones while tert-butylcyanoketene reacts with N-methyl- and N-ethylnitrones to afford isoxazolidinones.

■ Structures of Ajacusine and Ajadine, Two New C₁₉-Diterpenoid Alkaloids from Delphinium ajacis L.

S. William Pelletier* and Rajinder S. Sawhney

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

Abstract

The complete structures of two new diterpenoid alkaloids, ajacusine (1) and ajadine (2), have been established by physico-chemical methods.

■ The Optical Resolution of 1-Aryl-4,6-dimethyl-2(1H)-pyrimidiniones

Choji Kashima,* Akira Katoh, Yoshimori Omote, and Yoshiro Nakata

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

Abstract

By the recrystallization of the salts with d-camphor-10-sulfonic acid, ortho substituted 1-aryl-4,6-dimethyl-2(1H)-pyrimidinones could succeed to separate the atropisomers.

■ Sterically Controlled Synthesis of cis-1-Benzyl-2-methoxycarbonyl-3-phenylaziridine

Isao Nakamura and Kaoru Harada*

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

Abstract

The treatment of methyl erythro-2,3-dibromo-3-phenylpropionate (I), methyl cis- and trans-α-bromocinnamate (IIa, IIb) with benzylamine resulted in the formation of the same sole product cis-1-benzyl-2-methoxycarbonyl-3-phenylaziridine (III). A plausible stereochemical pathway was discussed. The compound III was converted to phenylalanine (V) by hydrogenation and threo-β-phenylserine (VI) by hydration reaction.

■ Selectivity on the Homolytic Acylation of Pyrimidine Derivatives

Takao Sakamoto, Takeji Sakasai, and Hiroshi Yamanaka*

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

Abstract

Pyrimidine derivatives in which 2- and 4-positions are free, exhibited regioselectivity toward the reaction with acyl radicals. Namely, 6-phenyl-, 6-methylpyrimidine and 5,6,7,8-tetrahydroquinazoline reacted with the acyl radicals generated from aldehydes, ferrous sulfate, t-butyl hydroperoxide, and sulfuric acid to sulfate, t-butyl hydroperoxide, and sulfuric acid to give the 4-acyl derivatives, respectively. In all the cases, the formation of 2-acyl isomers was not observed.

■ Synthesis of Trisubstitutes Dibenzazonine Alkaloids: Laurifine, Laurifinine and Laurifonine

Kazuo Ito,* Hitoshi Tanaka, and Masayoshi Shibata

*Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku, Nagoya 468-8503, Japan

Abstract

Irradiation of sodium salt of the phenolic bromo-compound (6) in methanol solution gave a mixture of three products (7, 8 and 9). Treatment of one of the photocyclization products (9) with methyl iodide-potassium carbonate followed by hydroboration with diborane afforded laurifine (II), which was readily converted into laurifonine (12) by N-methylation with formaldehyde-sodium borohydride. On the other hand, 9 was reduced with diborane to provide the secondary amine (13), and 13 was subsequently N-methylated to yield laurifinine (14). The synthetical laurifinine (14) was identical with natural laurifinine by comparison of various spectral data (ir, nmr and mass spectra) and t.l.c. behavior.

■ Studies on the Synthesis of Bisindole Alkaloids. XIII. A Synthesis of Catharine

James P. Kutney,* John Balsevich, and Brian R. Worth

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

Abstract

Oxidation of leurosine with t-butyl hydroperoxide provided the first synthesis of the alkaloid catharine. Some evidence for a radical promoted mechanism is given. A correction to an earlier structural assignment is made.

■ Chemical Transformation of α-Santonin into Sesquiterpene α-Methylene-γ-lactones, Douflanine, and Ludovicin A and B

Koji Yamakawa,* Kiyoshi Nishitani, and Kazutoyo Azusawa

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

Abstract

Eudesman type α-methylene-γ-lactones, douglanine (3), ludovicin A and B (4 and 5) have been synthesized from α-santonin (1). Enone (6) was reduced with LiAlH (OBu^t)₃ to give alcohols (7a) and (8a) in 6 : 1 ratio. Phenylselenenylation of 8a afforded a selenide (11). Oxidative elimination of 11 with 2 eq. H₂O₂ gave douglanine (3), while 11 was treated with an excess H₂O₂ to afford ludovicin A and B (4 and 5).

■ Photochemical Ring Contraction of 4-Pyrimidone. Formation of β-Lactam

Takao Yamazaki,* Masanori Nagata, Shun-ichi Hirokami, Yoshiro Hirai, and Tadamasa Date

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

■ Carbon-13 Nuclear Magnectic Resonance Spectroscopy of Quinolizidine Derivatives

Dirk Tourwé and Georges Van Binst*

*Laboratoium voor organische Chemie, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussel, Belgium