HETEROCYCLES

■ Contents

■ Asymmetric Synthesis of Homoisoflavanone Using Lipase-catalyzed Reaction

Masashi Kawasaki,* Naoki Toyooka, Yoshinori Matsui, Akira Tanaka, Michimasa Goto, Hiroko Kakuda, Shigeki Kawabata, and Tadashi Kometani

*Department of Liberal Arts and Sciences, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Kosugi-Machi, Toyama-Ken 939-0398, Japan

Abstract

The (R)- and (S)-enantiomers of 3-benzyl-4-chromanone (homoisoflavanone) were synthesized starting with the optically active 2-benzyl-1,3-propanediol monoacetates, which were obtained via the lipase-catalyzed enantioselective reaction.

■ A One-Pot Synthesis of 3,4-Dihydropyrimidin-2-(1H)-ones from Primary Alcohols Promoted by Bi(NO₃)₃·5H₂O in Two Different Media: Organic Solvent and Ionic Liquid

Ahmad R. Khosropour,* Mohammd M. Khodaei,* Mojtaba Beygzadeh, and Mahbubeh Jokar

*Department of Chemistry, Faculty of Science, Razi University, Kermanshah 67149, Iran

Abstract

A new, simple and efficient procedure for the one-pot conversion of alcohols instead of aldehydes to the corresponding 3,4-dihydropyrimidin-2(1H)- ones (DHPMs) with Bi(NO₃)₃.5H₂O as a commercially available, inexpensive, stable and non-toxic reagent in two media, acetonitrile (as an organic solvent) and tetrabutylammonium bromide (as an ionic liquid) is described. This one-pot oxidation-cyclocondensation reaction is performed without isolation of any intermediate (aldehyde) and thus reducing time, saving energy and raw materials. On the other hand treatment of primary alcohols with this new one-pot method produce the dehydropyrimidinones in higher yields than those are obtained in the traditional method.

■ Four New Steroidal Saponins from the Rhizomes of Helleborus orientalis

Kazuki Watanabe, Hiroshi Sakagami, and Yoshihiro Mimaki*

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

Abstract

A phytochemical analysis has been carried out on the glycoside-enriched fraction of a MeOH extract of Helleborus orientalis rhizomes, resulting in the isolation of two new bisdesmosidic furostanol saponins (1 and 2) and two new furospirostanol saponins (3 and 4). The structures of 1-4 were determined on the basis of extensive spectroscopic analysis and acid hydrolysis followed by chromatographic and spectroscopic analysis. Compound (3) showed moderate cytotoxic activity against HSC-2 human squamous cell carcinoma cells with an IC₅₀ value of 16 μg/mL.

■ Synthesis and Comparative Cytostatic Activity of the New N-7 Acyclic Purine Nucleoside Analogues with Natural N-9 Regioisomers

Svjetlana Prekupec, Blanka Kalokira, Mira Grdisa, Kresimir Pavelic, Erik De Clercq, Mladen Mintas, and Silvana Raic-Malic*

*Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulicev trg 20, HR-10000 Zagreb, Croatia

Abstract

The synthesis of the purine derivatives alkylated at N-7 (2a) and N-9 (2b) with 2-acetoxyethoxymethyl side chain, and chemical transformations of keto to chloro (5a), chloro to thio (6a) at C-6, and amino to fluoro (7a) at C-2 position of the purine ring were described. Structures of compounds were elucidated by analysis of their ¹H and ¹³C NMR spectra, MS spectra and elemental analyses. N-7 Regioisomers (2a-7a) were evaluated for their cytostatic activities and their inhibitory effects were compared with those of the corresponding N-9 isomers. The 2-aminopurin-6-thione derivative (6a) showed the highest cytostatic activity, particularly against murine leukemia (L1210).

■ Hydrogen Bonding and Conformation of 5-Substituted Dipyrromethanes — A Solid State Study

Mathias O. Senge

*Department of Chemistry, Trinity College Dublin, Dublin 2, Ireland

Abstract

A crystallographic study of nine different meso-substituted dipyrromethanes identifies the main types of intra- and intermolecular hydrogen bonding pattern in this class of porphyrin building blocks. Most compounds form similar hydrogen-bonded dimers in the crystal but distinct differences in the dipyrromethane conformations are observed in dependence on the type of the meso substituent.

■ New Labdane-Type Diterpenoids from Croton oblongifolius and Their Cytotoxic Activity

Chaiyo Chaichantipyuth,* Amorn Petsom, Pagorn Taweechotipatr, Nongnuj Muangsin, Narongsak Chaichit, Songchan Puthong, Sophon Roengsumran, Masatoshi Kawahata, Toshiko Watanabe, and Tsutomu Ishikawa

*Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi, Inage, Chiba 263-8522, Japan

Abstract

Eight new labdane-type diterpenoids (1-3) and (5-9) and hardwickiic acid (4), a clerodane, were isolated from the stem bark of Croton oblongifolius. Their structures were established to be 3-oxygenated ent-manoyl oxide derivatives with a 8,13-epoxytricyclic ring system and hydroxylabdandienes on the basis of spectroscopic and X-Ray crystallographic analysis. The absolute stereochemistry of the core labdane skeleton was deduced to be (5S,8S,9S,10R,13S) from the X-Ray crystallographic analysis of the p-bromobenzoate of ent-3α-hydroxymanoyl oxide (3) and mutual chemical correlation. Cytotoxicity of these compounds was tested against a panel of human tumor cell lines.

■ Yb(OTf)₃-catalyzed Vinylogous Mannich Reaction of Trialkylsilyloxyfuran

Sylvain Oudeyer, Bruno Dudot, and Jacques Royer*

*CNRS-University Paris5, Faculty of Pharmacy, 4 avenue de l’Observatoire, 75270 Paris Cedex 06, France

Abstract

The one-pot three-component vinylogous Mannich reaction of trialkylsilyloxyfurans with anilines and aldehydes in the presence of catalytic amounts of Yb(OTf)₃ gave the substituted aminoalkyl-butenolides in good yields (> 90 %) and diastereoselectivities (d.e. > 60 %). The configuration of the major product is erythro (anti) and was confirmed by chemical transformation into piperidinone derivatives and ¹H NMR spectral studies of the latter compounds. The vinylogous Mannich reaction performed with preformed imines proceeded similarly with a preferred erythro selectivity while the condensation of 3-methyl-2-trialkylsilyloxyfurans was threo selective.

■ Novel Synthetic Route of Coelenterazines -2-: Synthesis of Various Dehydrocoelenterazine Analogs

Nobuhiro Kondo, Masaki Kuse, Thumnoon Mutarapat, Nopporn Thasana, and Minoru Isobe*

*Laboratory of Organic Chemistry, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8601, Japan

Abstract

The novel synthetic route to introduce various substituents into 5-position of coelenteramine is described. Difficulties, however, are observed in the attempted synthesis of some analogs having labile functional groups. This is due to the strong acid conc. H₂SO₄ after Suzuki-Miyaura coupling, so that the route was limited only to the synthesis for aminopyrazines having acid-stable functional groups. In this report, we describe alternative success in the deprotection of N-tosyl-animopyrazine triflate before the cross coupling; thus, we obtained the aminopyrazine triflate in high yield. This compound enables us to synthesize various coelenterazine analogs. This triflate was proven to be so important intermediate that the versatile synthesis for coelenterazine and dehydrocoelenterazine analogs was established through Suzuki-Miyaura or Sonogashira coupling.

■ Withanolides from Datura innoxia

Bina S. Siddiqui,* Shamsul Arfeen, Farhana Afshan, and Sabira Begum

*International Centre for Chemical Sciences, H. E. J. Research Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan

Abstract

The methanolic extract of the aerial parts of Datura innoxia afforded two new withanolides namely witharifeen (1) and daturalicin (2). Their structures were established as 11α, 12β-dihydroxy (20R, 22R)-21,24-epoxy-1-oxowitha-2, 5, 25(27)-trien-22, 26-olide (1) and (20R, 22R)-5β, 6β -14α,15α -21,24-triepoxy-1-oxowitha-2,25(27)-dien-22,26-olide (2) respectively by analysis of spectroscopic data.

■ Microwave-assisted Aromatization of 1,3,5-Trisubstituted 2-Pyrazolines by Silica-supported N-Bromosuccinimide as a Useful Reagent under Solvent Free ‘Dry’ Condition

Davood Azarifar* and Behrooz Maleki

*Department of Chemistry, School of Science, Bu-Ali Sina University, Hamadan 65174, Iran

Abstract

An efficient aromatization of 1,3,5-trisubstituted 2-pyrazolines to their corresponding pyrazoles by NBS was carried out under microwave irradiation and solvent-free conditions in moderate yields. It has also been observed that, by activating the NBS reagent on silica gel as a support the reaction times can be dramatically reduced and good yields are obtained.

■ Two New Isoflavonoids and a New 2-Arylbenzofuran from the Roots of Erythrina variegata

Hitoshi Tanaka,* Masaru Sudo, Miyuki Hirata, Magoichi Sako, Masaru Sato, Ih-Sheng Chen, and Toshio Fukai

*Faculty of Pharmacy, Meijo University, Yagoto, Tempaku-ku, Nagoya 468-8503, Japan

Abstract

Two new isoflavonoids, eryvarins S (1) and T (2), and a new 2-arylbenzofuran, eryvarin U (3), together with nine known compounds, were isolated from the roots of Erythrina variegata. Their structures were established on the basis of spectroscopic analysis. Eryvarin U is a rare naturally-occurring 2-arylbenzofuran. The antibacterial activity of these three new compounds against 13 strains of methicillin-resistant Staphylococcus aureus (MRSA) was examined in which eryvarin U showed the highest antibacterial activity.

■ Synthesis of Benzoporphyrins with One or Two Meso-Substitutents via Substitution Reactions

Mathias O. Senge* and Ines Bischoff

*Department of Chemistry, Trinity College Dublin, Dublin 2, Ireland

Abstract

Reaction of either free base benzoporphyrin, its zinc(II) complex or β-bicyclo(2,2,2)octeno appended precursor porphyrins with LiR reagents gave an entry into mono- and soluble di-meso-substituted benzoporphyrins.

■ Eremopetasitenin A₃ and 8-Oxoeremophil-6-en-12-oic Acid from Petasites japonicus ssp. giganteus

Motoo Tori,* Moeko Kume, Katsuyuki Nakashima, Masakazu Sono, and Masami Tanaka

*Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima, 770-8514, Japan

Abstract

Seven eremophilane-type sesquiterpenes have been isolated from Petasites japonicus ssp. giganteus collected in Hokkaido, and two of them have been found to be new. Eremopetasitenin A₃ was a lactone containing an epoxide at the C-7 and C-8 positions, whose structure was established mainly based on spectroscopic evidence including 2D NMR spectra. The other one was an eremophilane-type carboxylic acid.

■ Isolation of New Isoflavonolignans, Butesuperins A and B, from a Thai Miracle Herb, Butea superba

Kai Ma, Tsutomu Ishikawa,* Hiroko Seki, Kazuo Furihata, Hiroshi Ueki, Shizuo Narimatsu, Yoshihiro Higuchi, and Chaiyo Chaichantipyuth

*Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi, Inage, Chiba 263-8522, Japan

Abstract

Two new isoflavonolignans, designated as butesuperins A and B, were isolated from the active fraction of the root of Butea superba for PDE inhibition together with eight known isoflavone derivatives.

■ Fused Quinolines. Recent Synthetic Approaches to Azoloquinolines. A Review

Mohamed Abass

*Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, 11711 Cairo, Egypt

Abstract

Azoloquinoline derivatives such as pyrrolo-, furo-, thienoquinolines and their benzo or heterocyclic annelated derivatives have attracted interest for their important biological applications. This review highlights the recent synthetic approaches to various azoloquinolines.