HETEROCYCLES

■ Contents

■ Formation of 3,4,5,6-Tetrahydro-7-hydroxy-6-methyl-1H-azepino[5,4,3-cd]indole in the Reaction of Serotonin with Acetaldehyde in Water in the Presence of Either L-Amino Acid, Nicotine or Fluoride

Masanori Somei* and Minoru Seto

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

Abstract

Possible formation of a new compound, 3,4,5,6-tetrahydro-7-hydroxy-6-methyl-1H-azepino[5,4,3-cd]indole (4a), in serotonergic neuron after drinking ethanol is chemically suggested by reacting serotonin with acetaldehyde in water in the presence of either L-amino acid, nicotine or fluoride.

■ A Study of the Alkylation and Rearrangement Products of Chiral 1,3-Oxazolidine- and Thiazolidine-2-thiones

Raphaël Robiette, Anny Dekoker-Malengreau, and Jacqueline Marchand-Brynaert*

*Department of Organic and Medical Chemistry, Catholic University of Louvain, Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium

Abstract

Homochiral 1,3-oxazolidine-2-thiones and 1,3-thiazolidine-2-thiones are useful chiral auxiliaries in asymmetric synthesis. Our interest in chiral amino dienes drove us to consider the preparation of dienes (1a) and (1b) bearing those auxiliaries. Trying to synthesize such dienes by alkylation of the corresponding heterocycles with 1,4-dihalogeno-2-butenes, we found several rearrangement reactions leading to new compounds that we fully characterized. In particular, we found a new access towards 4-vinyl-1,3-thiazolidin-2-ones.

■ Synthesis of Quinoxaline 1,4-Dioxides from Benzofuroxan Proceeds Not in, But on Zeolite

Tohru Takabatake,* Hiroyasu Ito, Aki Takei, Tomoyuki Miyazawa, Minoru Hasegawa, and Shinichi Miyairi

*College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan

Abstract

Quinoxaline synthesis using Na-zeolite A as a catalyst to proceeds in a better yield than that using zeolite X. The pore diameter of zeolite X is large enough to allow the benzofuroxan derivatives access to cages, therefore part of benzofuroxan is adsorbed in the internal surface of zeolite X. Whereas the windows to the cages of Na-zeolite A are too small to allow the benzofuroxan derivatives access to the cages, therefore all the benzofuroxan is adsorbed on the external surface of zeolite. The reactions of benzofuroxans with benzoylacetone was catalyzed by zeolite proceed not in, but on zeolite.

■ Photochemistry of Heterocyclic Enaminones: An Alternative and Efficient Route to Cryptolepine Alkaloid Framework

Pierre-Jean Aragon, Jean-Michel Chezal, Olivier Chavignon, Jean-Claude Teulade, and Yves Blache*

*E. A. 2414 Pharmacochimie et Biomolécules, Laboratoire de Chimie Organique Pharmaceutique, Université Montpellier I, 15 Avenue Charles Flahault, 34060 Montpellier, France

Abstract

Photochemical reactivity of heterocyclic enaminone is described in view of the synthesis of cryptolepine analogs (5). The reaction conditions are shown to have some influence on the regioselectivity as well as the yields of photocyclization.

■ One-Pot Dry Media Synthesis of New Tetracyclic 1,5-Benzothiazepines under Microwave Activation

Anshu Dandia,* Meha Sati, Kapil Arya, and André Loupy*

*Laboratoire des Réactions Sélectives sur Supports, ICMMO, CNRS UMR 8615, Université de Paris-Sud, Bâtiment 410, 91405 Orsay Cedex, France

Abstract

Green chemical approaches to the condensation reaction of substituted benzenethiols and 2-arylidene-1-tetralone as synthons for the syntheses of a series of new 7-phenyl-5,6,6a,7-tetrahydrobenzo[b]naphtho[1,2-e][1,4]thiazepines (4a-e) of biological importance are described. The reaction using montmorillonite KSF as an inorganic solid is accelerated under microwave irradiation. Details and advantages of this new, efficient, solvent-free protocol along with non-thermal specific microwave effects are underlined.

■ Acid Assisted Reactions of 1,2-Dihydro-2-(4,5-dihydroimidazol-2-yl)phthalazin-1-ol with Aryl(Heteroaryl) Methyl Ketones

Franciszek Saczewski,* Ewa Kobierska, Jacek Petrusewicz, Anna Gendzwill, and Maria Gdaniec

*Department of Chemical Technology of Drug, Medical University of Gdansk, 107 Gen.J. Hallera Str., 80-416 Gdansk, Poland

Abstract

A series of the 1-[2-(4,5-dihydro-1H-imidazol-2-yl)-1,2-dihydrophthalazin-1-yl]-2-arylethanone hydrochlorides (2a-i) was synthesized by acid assisted reaction of phthalazine pseudobase (1) with aryl(heteroaryl) methyl ketones. A similar reactions of 1 with cyclohexanone and benzo-1,4-dioxan-2-one afforded 1, 2, 3, 4, 6, 7, 15b, 15c-octahydro-4aH-imidazo[1,2-a]phthalazino[2,1-c]quinazolin-4a-ol (5) and 7-[2-(4,5-dihydro-1H-imidazol-2-yl)-1,2-dihydro-phthalazin-1-yl]-1,4-benzodioxin-2(3H)-one (6), respectively. Structures of these compounds were confirmed by IR and NMR spectroscopy as well as X-Ray crystallographic analysis of the free base (3a). Biological activity of the compounds (2) was examined on rabbit aortic rings.

■ 1-Methyl-3-trimethylsilylparabanic Acid as an Effective Reagent for the Preparation of N-Substituted (1-Methyl-2,5-dioxo-1,2,5H-imidazolin-4-yl)amines and Its Application to the Total Synthesis of Isonaamidines A and C, Antitumor Imidazole Alkaloids

Seikou Nakamura, Ikuo Kawasaki, Masayuki Yamashita, and Shunsaku Ohta*

*Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan

Abstract

1-Methyl-3-trimethylsilylparabanic acid (17) was successfully used in the final step of the total synthesis of isonaamidine A (9), isonaamidine C (11) and pyronaamidine (8), antitumor marine imidazole alkaloids.

■ Two Dihydropyranocoumarins from Peucedanum wawrii

Ling-Yi Kong,* Xian-Li Wu, and Masatake Niwa

*Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China

Abstract

Two dihydropyranocoumarins were isolated from the root of Peucedanum wawrii and the structures were established as 3’(R)-acetoxy-3’,4’-dihydroxanthyletin (1) and 3’(R)-acetoxy-4’(S)-angeloyloxy-3’,4’-dihydroseselin (2), respectively, by spectroscopic methods. The absolute configurations were deduced by chemical correlations with known compounds.

■ Synthesis and Identification of a Novel 6,5,6-Tricyclic Lactam

Joel P. Cooper,* Jeff E. Cobb, Barry G. Shearer, Douglas J. Minick, and Randy D. Rutkowske

*Department of Medicinal Chemistry, GlaxoSmithKline, Five Moore Drive, P.O. Box 13398, Research Triangle Park, North Carolina, 27709-3398, U.S.A.

Abstract

While incorporating oxazoles into known PPARγ agonist an unexpected 6,5,6-tricylic lactam was isolated as the major product.

■ On the Synthesis of Two Dimethoxy-1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinoline Regioisomers

Sarah Chackal, Fabienne Dudouit, Raymond Houssin, and Jean-Pierre Hénichart*

*Institut de Chimie Pharmaceutique, Albert Lespagnol, EA 2692, Université de Lille 2, 3, rue du Professeur Laguesse, BP 83, 59006 Lille Cedex, France

Abstract

Many marine alkaloids are biologically active products and possess the 1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinoline core as a common feature. This is a report of the synthesis of two of the title molecules with confirmation of their structure.

■ New Sesquiterpene Lactones from Hemisteptia lyrata Bunge

Tae Joung Ha, Ki Hun Park, Dae Sik Jang, Jong Rok Lee, Ki Min Park, and Min Suk Yang*

*Department of Agricultural Chemistry, Division of Applied Life Science, Gyeongsang National University, Chinju, 660-701, Korea

Abstract

From the flowers of Hemisteptia lyrata, two new and two known guaianolides were isolated. The structures and relative configuration of the new compounds were established as 8α-O-2-hydroxymethyl-2-propenoyl-3β-hydroxy-13-methoxy-4(15),10(14)-guaiadien-12,6-olide (1) and 3β,8α-dihydroxy-13-methoxy-4(15),10(14)-guaiadien-12,6-olide (2), together with known compounds, isoamberboin (3) and 11,13-dihydro-deacylcynaropicrin (4). The structures were established by spectral data and X-Ray diffraction analysis.

■ New C₁₉-Diterpenoid Alkaloids from Aconitum liljestrandii

Guang-Bo Xie, Qiao-Hong Chen, Dong-Lin Chen, Xi-Xian Jian, and Feng-Peng Wang*

*Department of Chemistry of Medicinal Natural Products, West China College of Pharmacy, Sichuan University, No. 17, Duan 3, Remin Nan Road, Chengdu 610041, China

Abstract

Two new C₁₉-diterpenoid alkaloids, liljestrandinine (1) and N-deethyltalatisamine (2) were isolated from the roots of Aconitum liljestrandii along with five known C₁₉-diterpenoid alkaloids: chasmaconitine (4), forestine (5), pengshenine B (6), cammaconine (7), and 6-epi-foresticine (8). Structures were established by spectroscopic method including 2D NMR.

■ meta-Substituent Effects on the Photocyclization of Aryl-substituted N-Acyl-α-dehydroalanine Derivatives

Kei Maekawa, Hiroo Kajiwara, Yoshiyuki Iseya, Tetsutaro Igarashi, and Tadamitsu Sakurai*

*Departmnet of Applied Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan

Abstract

On irradiation in methanol, the title compounds having chloro, trifluoromethyl or methyl group at the meta position on the styryl benzene ring gave 6-substituted (2) and 8-substituted (3) 1-methyl-3-(methylaminocarbonyl)isoquinolines along with 1-azetines. The preferential formation of 2 to 3 was explained in terms of steric effects on the cyclization process from the excited-state (Z)-isomer. The methoxy group introduced at the same meta position exerted dramatical electronic and steric effects on the excited-state cyclization pathway giving rise to regioselectively 6-substituted 2-quinolinone and isoquinoline derivatives. The 1-naphthyl substituent in the title compounds was found to have the same effects on the cyclization pathway as the methoxyphenyl group.

■ New Oleanane-Type Triterpene Saponins from Millettia speciosa

Taketo Uchiyama, Masakatsu Furukawa, Sachi Isobe, Mitsuko Makino, Toshiyuki Akiyama, Tetsuo Koyama, and Yasuo Fujimoto*

*College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan

Abstract

The 70% ethanol extract of the roots of Millettia speciosa gave two new oleanane-type saponins along with two known pterocarpans, medicarpin and maackiain. The structures of new compounds were established on the basis of chemical and spectroscopic evidences. Medicarpin and maackiain showed cytotoxicity against leukemia cells (HL-60) and inhibited leukotrine secretion from RBL-2H3 cells.

■ Methods for the Synthesis of Oligothiophenes

Edmunds Lukevics,* Pavel Arsenyan, and Olga Pudova

*Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga, LV-1006, Latvia

Abstract

Methods of synthesis of oligothiophenes using thiophene lithium, copper, magnesium, zinc, boron, silicon and tin derivatives and also cyclization reactions have been reviewed.

■ Terpenoid Coumarins of the Genus Ferula

Mohamed H. Abd El-Razek, Shinji Ohta, and Toshifumi Hirata*

*Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-hiroshima, Hiroshima 739-8526, Japan

Abstract

Chemical studies on the plants of the genus Ferula (Apiaceae) show the presence of many compounds belonging mainly to the groups of monoterpene coumarins, sesquiterpene coumarins, sesquiterpenes, furanocoumarins and aromatic compounds. Biological studies reveal significant activities, such as an anti-HIV activity, inhibition of cytokine release and early events of carcinogenesis. Extracts of some species of Ferula have long been used in folk medicine for treating various diseases, possess an antimicrobial and estrogenic actions, and are natural plant growth inhibitors and stimulators.