HETEROCYCLES

■ Contents

■ Total Synthesis of Decahydrobenzo[d]xanthene Sesquiterpenoids Aureol, Strongylin A, and Stachyflin: Development of a New Strategy for the Construction of a Common Tetracyclic Core Structure

Tadashi Katoh*

*Department of Synthetic Organic Chemistry, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan

Abstract

In this article, the total synthesis of rearranged sesquiterpenoid hydroquinones—aureol, strongylin A, and stachyflin—is reviewed with a particular focus on their methodology and strategy.

■ Recent Syntheses of Proanthocyanidins

Hidefumi Makabe*

*Sciences of Functional Foods, Graduate School of Agriculture, Shinshu University, 8304 Minamiminowa-mura, Kamiina-gun, Nagano 399-4598, Japan

Abstract

Recently proanthocyanidins have been paid much attention due to their significant biological activities and health benefitical effects. The author reviewed recent progress of the syntheses of proanthocyanidins including our work within this decade.

■ A Novel Synthetic Approach towards 1H-Pyrazole-5-carboxylic Acid Derivatives Using 4-(4-Methylbenzoyl)-5-(4-methylphenyl)furan-2,3-dione

Elif Korkusuz,* Ismail Yıldırım, and Ertan Şahin

*Kayseri Vocational College, Erciyes University, Kayseri 38039, Turkey

Abstract

The 1H-pyrazole-5-carboxylic acid derivatives were obtained by reactions of 4-(4-methylbenzoyl)-5-(4-methylphenyl)furan-2,3-dione with 2,4-dinitrophenyhydrazine. So, new derivatives of 1H-pyrazole-5-carboxylic acid which are potential biological active compounds, were synthesized for the first time. The structures of all new synthesized products were characterized by IR, 1H-, 13C NMR, APT, and 2D NMR (HETCOR, COSY) spectroscopic data and elemental.

■ Synthesis of Tetrasubstituted Pyrrolidine Derivatives Employing β-Lactam as a Chiral Building Block

Genta Tadano, Koji Ishikura, and Keiji Tanino*

*Department of Chemistry, Graduate School of Science, Hokkaido University, Kita 10 Nishi 8, Kita-ku, Sapporo, Hokkaido 060-0810, Japan

Abstract

A new method for constructing tetrasubstituted pyrrolidine derivatives using the known β-lactam as a chiral building block was developed. After construction of a carbapenem skeleton, the β-lactam moiety was cleaved to afford a multi-substituted pyrrolidine. The present method was employed for the synthesis of A-315675 analogs 1 and 2.

■ SYNTHESIS OF NOVEL ANTIBACTERIAL METAL FREE AND METALLOPHTHALOCYANINES APPENDING WITH FOUR PERIPHERAL COUMARIN DERIVATIVES AND THEIR SEPARATION OF STRUCTURAL ISOMERS

Rawdha Medyouni, Naceur Hamdi,* Anis Ben Hsouna, Abdullah Sulaiman Al-Ayed, Hussain Ali Soleiman, Fethi Zaghrouba, and Christian Bruneau

*Chemistry Department, College of Science, Qassim University, P.O.Box 8000, Saudi Arabia

Abstract

The preparation of novel metal-free phthalocyanine and metallophthalocyanine complexes 6 and 7 (MPcs, M = Co, Zn, Cu and Mn), with four peripheral 6-hydroxy-4-methylcoumarin and 6-hydroxycoumarin substituents, were prepared and characterized by cyclotetramerization of compounds 4 and 5 with the corresponding metal salts (Zn(OAc)2·2H2O, Co(OAc)2·4H2O, CuCl, Mn(OAc)2·4H2O) as a template for macrocycle formation in 2-(N,N-dimethylamino)ethanol whereby a mixture of four different structural isomers are obtained; two of these isomers, with C2"- and Cs,symmetry are isolated by HPLC and characterized by FT-IR, UV-vis, elemental analyses, 1H NMR and 13C NMR spectroscopies. The electronic spectra exhibit a band of coumarin identity together with characteristic bands of the phthalocyanine core. The new compounds were screened for antibacterial activity. Most of them are more active against E. coli and S. aureus .

■ Synthesis and in vitro Antitumor Effect of New Vindoline Derivatives Coupled with Amino Acid Esters

Péter Keglevich, László Hazai, Álmos Gorka-Kereskényi, Lilla Péter, Judit Gyenese, Zsófia Lengyel, György Kalaus, Zsófia Dubrovay, Miklós Dékány, Erika Orbán, Ildikó Szabó, Zoltán Bánóczi, Csaba Szántay, Jr., and Csaba Szántay*

*Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1111 Budapest, Szt. Gellért tér 4, Hungary

Abstract

10-Bromovindoline and its 14,15-dihydro- and 14,15-cyclopropano derivatives were coupled in the position 16 with (L)- and (D)-tryptophan methyl esters. The tryptophan derivatives of vindoline were synthesized starting from the 16-carboxylic acid hydrazides via the corresponding azides which were allowed to react with the amino acid esters. The new compounds showed antitumor activity against human leukemia (HL-60) cells in vitro.

■ Hydrazones and 1,3-Thiazolidin-4-ones Incorporating Furoxan Moiety Synthesized from Eugenol, the Main Constituent of Ocimum sanctum L. Oil

Nguyen Huu Dinh,* Trinh Thi Huan, Hoang Thi Tuyet Lan, and Sang-Bae Han

*Department of Chemistry, Hanoi National University of Education, 136 Xuanthuy Hanoi, Vietnam

Abstract

Two series of new hydrazones and 1,3-thiazolidin-4-ones incorporating furoxan moiety were synthesized from eugenol, the main component of Ocimum sanctum L. oil. The structure of these compounds was determined by IR, MS, 1H and 13C NMR analysis. All resonance signals of proton and carbon in the examined compounds are assigned using HSQC, HMBC and NOESY spectra. The hydrazones and the 1,3-thiazolidin-4-ones were tested for antimicrobial activities and almost all examined thiazolidinones displayed moderate activity against S. aureus and A. niger. Among screened hydrazones only one compound exhibited a significant cytotoxicity for human cancer cell line SW620.

■ Synthesis of 1,4-Diarylfluorenone and 1,4-Diarylfluorene

Yanmei Wang, Qiancai Liu,* Xiaoli Xiong, Shiming Deng, Jun Zhang, Min Zhu, and Hangmin Ge

*Department of Chemistry, East China Normal University, 500 Dongchuan Rd., Minhang, Shanghai 200241, China

Abstract

A novel synthetic route to 1,4-diarylfluorenone and 1,4-diarylfluorene is presented by starting with ninhydrin. The retro-Diels-Alder cycloaddition was employed as a key step to construct the target fluorenones, while a highly efficient reduction from 1,4-diarylfluorenones to 1,4-diarylfluorenes is developed by using of sodium sulfide nonahydrate as reductant. The final products are confirmed by 1H NMR, 13C NMR and mass spectrometry.

■ Synthesis of Some Pyrazole-Fused Pyrido[3,2-a]azulenes

Dao-Lin Wang,* Zhe Dong, Qing-Tao Cui, Fei-Fei Yang, and Wei Zhao

*Liaoning Key Laboratory of Synthesis and Application of Functional Compound, College of Chemistry & Chemical Engineering, Bohai University, Jinzhou 121001, China

Abstract

Facile synthesis of 11H(2H)-4-oxopyrazolo[3’,4’:6,5]pyrido[3,2-a]azulene-10-carboxylates (3) via a domino reaction of 3-(dimethylamino)-2-(2-methoxy-1-ethoxycarbonylazulen-3-oyl)acrylonitrile (1) with hydrazines (2) in moderate to good yields. This reaction provides a new procedure for synthesis of pyridinone-fused azulenes.

■ Efficient Organocatalytic Michael Addition Reaction of β−Ketoesters under High Pressure

Maya Moritaka, Keiji Nakano, Yoshiyasu Ichikawa, and Hiyoshizo Kotsuki*

*Laboratory of Natural Products Chemistry, Faculty of Science, Kochi University, 2-5-1, Akebono-cho, Kochi 780-8520, Japan

Abstract

The Michael addition reaction of β−ketoesters was efficiently promoted by a cooperative dual catalyst system composed by DMAP and thiourea A under high-pressure conditions (0.8 GPa) in toluene. The expected relatively congested adducts of 1,5-dicarbonyl compounds were prepared in high to excellent yield.

■ Synthesis of Dihydrooxepins by the Cycloaddition of 2-Amino-4,5-dihydro-3-furancarbonitriles with Dimethyl Acetylenedicarboxylate

Fumi Okabe, Hiroshi Maruoka,* Eiichi Masumoto, Toshihiro Fujioka, and Kenji Yamagata

*Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

Abstract

A facile and efficient synthesis of dihydrooxepins is described. Treatment of readily available 2-amino-4,5-dihydro-3-furancarbonitriles with dimethyl acetylenedicarboxylate at room temperature caused smoothly a cycloaddition reaction, followed by a ring expansion, giving the corresponding dihydrooxepin derivatives.

■ A New Method for Synthesis and Angiogenic Evaluation of Leteprinim Potassium and Its Novel Analogs

Norikazu Sakakibara, Ikuko Tsukamoto, Yohei Isono, Maki Takata, Ryoji Konishi, Yoshihisa Kato, and Tokumi Maruyama*

*Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, 1314-1 Shido, Sanuki City, Kagawa 769-2193, Japan

Abstract

We developed a novel pathway for the successful synthesis of leteprinim potassium 1, which is one of the candidate substances for treating Alzheimer’s disease, and subsequently synthesized 4 types of corresponding novel derivatives 2–5 that have hypoxanthine or 2-chloro-6-aminopurine as the nucleobase. We then determined the angiogenic activity of these compounds by using human umbilical vein endothelial cells. Compounds 1–4 showed no angiogenic potencies judging from statistical analysis, student’s t-test.

■ Design and Synthesis of New Hybrid Triazine-Indole Derivatives as Potential Antimicrobial Agents against Hospital Resistant Strains

Raed Al-Qawasmeh,* Monther A. Khanfar, Mohamad H. Semreen, Raed Abu Odeh, and Taleb H. Al-Tel

*Department of Chemistry, Faculty of Science, The University of Jordan, Amman 11942, Jordan

Abstract

A new series of antimicrobial [2-(5,6-diaryl-1,2,4-triazin-3-yl)-1H-indole] have been synthesized via microwave technology. The synthesized compounds were found to be potent against various clinical isolates of Gram-positive and Gram-negative bacteria as well as hospital resistant strains, MRSA and MSSA when compared to the drugs Cephtriaxone, Gentamycin and Levofloxacin.

■ Allylation of N,N-Acetal Derivatives Using Allyl Tin Regent in the Presence of Aluminum Chloride

Xiaonan Sun, Takanori Obu, Tatsuro Kijima, Satoshi Murakami, Shigeru Matsuba, Miho Kusakari, and Bunpei Hatano*

*Graduate School of Science and Engineering, Yamagata University, 3-16 Jonan 4-Chome, Yonezawa 992-8510, Japan

Abstract

Allylation of N,N-acetal derivatives proceeded efficiently using allyl tin regent in the presence of aluminum chloride, giving homoallylamines in good yields. This allylation was applied for N,S-acetals to give the corresponding homoallylamines.