HETEROCYCLES

■ Contents

■ The Pseudo-Intramolecular Process: A Novel Synthetic Method for Functionalized Heterocyclic Compounds

Nagatoshi Nishiwaki*

*School of Science and Technology, Kochi University of Technology, Tosayamada-cho, Kochi, 782-8502, Japan

Abstract

A pseudo-intramolecular process has been developed. Compounds having both an acidic hydrogen and a functionality serve as substrates in the present method, and immediately form an ammonium salt after the addition of an amine. When the amine is liberated under mild equilibrium conditions, both the nucleophilic amine and the electrophilic substrate are in proximity and efficiently react under mild reaction conditions. Although the reaction actually concerns an intermolecular process, it proceeds as if it were an intramolecular process. Thus, this method forms a novel procedure for synthesizing polyfunctionalized compounds that are not easily available via alternative methods.

■ Boroxine Chemistry: From Fundamental Studies to Applications in Supramolecular and Synthetic Organic Chemistry

Yuji Tokunaga*

*Department of Materials Science and Engineering, Faculty of Engineering, Fukui University, Bunkyo, Fukui 910-8507, Japan

Abstract

Organoboroxine chemistry has recently received much attention because the boroxine formation reaction is a powerful tool for the construction of organized architectures. The reversible nature of this reaction may result in new materials that possess unprecedented levels of structural organization due to facilitation through self-correction, and switchable properties can be imparted by the reaction’s reversibility. In addition, the effectiveness of boroxines (especially arylboroxines) has been recognised in the field of organic synthesis. The chemical properties of boroxines are certainly of great interest in organic synthesis and in the creation of new organic compounds. In this review, I describe the development of various molecular architectures that originate from the fundamental properties and structures of boroxines; I also describe the use of boroxines as reagents and catalysts.

■ Post-Modification of Triazole-Linked Analogues of DNA for Positively Charged Variants

Tomoko Fujino, Yusuke Miyauchi, Nobuhide Tsunaka, Koudai Okada, and Hiroyuki Isobe*

*Department of Chemistry and Advanced Institute for Materials Research (WPI-AIMR), Tohoku University, Aoba-ku, Sendai 980-8578, Japan

Abstract

We report a concise post-modification method to convert an electroneutral triazole-linked DNA (TLDNA) to a positively charged triazolium-linked analogue, TLDNA+. A one-step methylation of oligothymine TLDNA successfully afforded TLDNA+ with a dramatic improvement in the solubility. The pentameric oligothymine TLDNA+ formed a stable triple helix with natural oligoadenine DNA as well as a mercury-mediated self-duplex.

■ New Diketopiperazine Derivatives from Culture Broth of Staphylococcus sp. Isolated from Corallina officinalis Lineaus

Amgad I. M. Khedr, Isao Kouno, Takashi Tanaka, and Koji Yamada*

*Graduate school of Biomedical Sciences, Nagasaki University, Bunkyo-machi 1-14, Nagasaki 852-8521, Japan

Abstract

Two new diketopiperazine derivatives, staphyloamides A (1), and B (2), have been isolated from the culture broth of Staphylococcus sp. (No. P-100826-4-6) derived from Corallina officinalis Lineaus, along with the known cyclo (L-pro-D-phe) (3), cyclo (D-6-Hypro-L-phe) (4), cyclo (L-pro-L-val) (5), cyclo (L-pro-L-phe) (6), cyclo (L-pro-L-tyr) (7), cyclo (L-pro-L-leu) (8), cyclo (L-pro-L-ala) (9), and bacillusamide B (10). These structures were elucidated by extensive spectroscopic methods. Antimicrobial activities of compounds 3–10 were done.

■ Enantioselective Fluorescence Recognition of Chiral Amines by N-Acyl-(S)-1-naphthylalanyl-(S)-phenylglycine and N-Acyl-(S)-1-naphthylalanyl-(S)-1-naphthylalanine Dipeptides Bridged by a 1,2-Phenylene or an Ethylene Spacer Chain

Tomoe Ishikawa, Miho Sonobe, Akinori Hayakawa, Tetsutaro Igarashi, and Tadamitsu Sakurai*

*Department of Material and Life Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan

Abstract

This study sought to support the development of enantioselective dipeptide fluorescence sensors by examining the ability of the N-acyl-(S)-1-naphthylalanyl-(S)-phenylglycine and N-acyl-(S)-1-naphthylalanyl-(S)-1-naphthylalanine dipeptides (bridged by the 1,2-phenylene or ethylene spacer chain) to discriminate between aliphatic amine-derived (S)- and (R)-enantiomers. The results indicated that both hydrogen-bonding interactions in the ground state and charge-transfer interactions in the excited state are involved in the fluorescence quenching of these bridged dipeptides by chiral amines to produce the upward curving Stern–Volmer plots. In addition, the numerical analysis of these plots led to the conclusion that the bridged naphthylalanylphenylglycine dipeptide shows the highest ability to differentiate the (S)-enantiomer from (R)-enantiomer when the emission of this dipeptide is quenched by chiral alaninols.

■ Synthesis and Characterization of 4-Substituted 1-(4-Halogenophenyl)pyrrolidin-2-ones with Azole and Azine Moieties

Rita Vaickelioniene, Vytautas Mickevicius,* and Gema Mikulskiene

*Department of Organic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19, Kaunas LT-50254, Lithuania

Abstract

4-Substituted 1-(4-fluoro- and 4-chlorophenyl)pyrrolidin-2-ones containing azole, oxadiazole, triazole, and triazine fragments have been synthesized, and the characterization of the obtained products is presented. The study compounds have been analyzed by elemental analysis, and the NMR, IR, MS techniques. The 1H/13C 2D (HETCOR), APT (13C) NMR methods, and molecular modeling (MM2) were used for structure elucidation in more complicated cases.

■ Studies on the Chemical Behavior of the Novel 6,8-Dibromo-7-hydroxychromone-3-carboxaldehyde towards Some Carbon Nucleophilic Reagents

Magdy A. Ibrahim,* Tarik E. Ali, Azza M. El-Kazak, and Amira M. Mohamed

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

Abstract

A novel 6,8-dibromo-7-hydroxychromone-3-carboxaldehyde (4) was prepared by the Vilsemier-Haack formylation of 3,5-dibromo-2,4-dihydroxy acetophenone (3). The chemical reactivity of carboxaldehyde 4 was studied towards some carbon nucleophiles as cyclic and acyclic active methylene nucleophiles and also 1,3-C,N- and 1,3-C,C-binucleophiles as a route to achieve ring transformation to produce a variety of heterocyclic systems. Structures of the newly synthesized products have been deduced on the basis of elemental analysis and spectral data.

■ Promoting Effects on Hepatocyte Growth Factor Production of Daphnane Diterpenoids from Daphne odora

Rie Nakasone, Manami Kurisu, Manami Onodera, Yusaku Miyamae, Daisuke Matsuura, Hirotoshi Kanatani, Shingo Yano, and Hideyuki Shigemori*

*Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Japan

Abstract

Five daphnane diterpenoids, gnidilatidin (1), gnidilatidin 20-palmitate (2), yuanhuajine (3), odoratrin (4), and synaptolepis factor K4 (5), isolated from Daphne odora were used to evaluate the promoting effect on hepatocyte growth factor (HGF) production in normal human dermal fibroblasts (NHDF). All the tested compounds except for 2 increased the amount of HGF production significantly. According to the structure-activity relationships of compounds 1-5 and the derivative 6, it was revealed that a hydroxy group at C-20 was essential for expression of HGF production promoting activity.

■ Two New Furofuran Lignans from Kandelia obovata

Haihan Nan,* Han Lin,* Zhuoquan Qian, and Haozhen Yin

*Department of Marine Science, Wenzhou Medical College, University-town, Wenzhou, Zhejiang 325035, China

Abstract

Two new furofuran lignans, named kandelisesquilignan A and kandelisesquilignan B, were isolated from the aerial part of Kandelia obovata, together with seven known compounds β-sitosterol, betulinic acid, daucosterol, friedelin, lupeol, apigenin and acacetin. Their structures were characterized on the basis of spectral data. The two new compounds showed significant antioxidant activity by the DPPH method (IC50 = 31.9 and 27.8 μg/mL).

■ One-Pot Synthesis of (Guaiazulen-1-yl)furan Derivatives from Guaiazulene and 1,4-Diaryl-2-butene-1,4-diones

Dao-Lin Wang,* Jia-Yi Yu, Jiao Xu,* and Zhe Dong

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

Abstract

A facile, convenient, efficient, and high yielding synthesis of 3-(guaiazulen-1-yl)furan derivatives (3) has been developed by the condensation of guaiazulene (1) with 1,4-diaryl-2-butene-1, 4-diones (2) as nucleophiles in the presence of p-toluenesulfonic acid as the catalyst.

■ A Facile Green Synthesis and Anti-Cancer Activity of bis-Arylhydrazononitriles, Triazolo[5,1-c][1,2,4]triazine, and 1,3,4-Thiadiazolines

Sobhi M. Gomha, Khaled D. Khalil, Ali M. El-Zanaty, and Sayed M. Riyadh*

*Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt

Abstract

Coupling of 2-cyanoacetyl-1-methyl-1H-pyrrole (1) with diazonium salts of 1,4-benzenediamine (2), 2,6-dichlorobenzene-1,4-diamine (4), and benzidine (6) afforded bis-arylhydrazononitriles 3, 5, and 7, respectively. Also, coupling of 1 with [1,2,4]triazole-3-diazonium sulfate (8) gave the respective [1,2,4]triazolo[5,1-c][1,2,4]triazine derivative 11. On the other hands, treatment of 2-[(1-methyl-1H-pyrrol-2-yl)carbonyl]-3-mercapto-3-(phenylamino)acrylonitrile (12) with hydrazonoyl chlorides 13a-h in dioxane, in the presence of chitosan as eco-friendly heterogeneous basic catalyst, under microwave irradiation furnished 1,3,4-thiadiazolines 16a-h, incorporating pyrrole moiety. The anti-cancer activities of the synthesized products were determined against the colon carcinoma (HCT), human laryngeal carcinoma (Hep-2), human medulloblastoma (Daoy), human breast adenocarcinoma (MCF-7), and human colon adenocarcinoma (WiDr) cell lines.

■ Facile Synthesis of Pyrido[1,2-a]benzimidazole Derivatives via Novel Tandem Reaction Involing Horner-Emmons Reaction

Wen-Jing Zhao, Ya-Fei Xie, Yan-Qing Ge,* Wei-Ren Xu, Gui-Long Zhao, and Jian-Wu Wang*

*School of Chemistry and Chemical Engineering, Shandong University, 27 Shanda Nanlu, Jinan,Shandong, 250100, China

Abstract

Pyrido[1,2-a]benzimidazole derivatives were conveniently synthesized by a novel tandem reaction under mild conditions. The reaction mechanism was also proposed.

■ New Xanthones from Garcinia bracteata and Their Cytotoxicities

Qiu-Fen Hu,* Deyun Niu, Xiangli Li, Yunhua Qin, Zongyan Yang, Guoli Zhao, Zhongxiu Yang, Xue-Mei Gao,* and Zhangyu Chen

*Key Laboratory of Ethnic Medicine Resource Chemistry, State Ethnic Affairs Commission & Ministry of Education, School of Chemistry and Biotechnology, Yunnan University of Nationalities, Kunming, Jingming South Road, Chenggong New District, Kunming, Yunnan 650500, China

Abstract

Two new xanthones, bracthones A (1) and B (2), together with four known xanthones (3-6) were isolated from the stems of Garcinia bracteata. Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D- NMR techniques. Compounds 1-6 were tested for their cytotoxicities against five human tumor cell lines (NB4, A549, SHSY5Y, PC3, and MCF7). Compounds 1 and 2 showed high cytotoxicities against PC3 cell with IC50 values of 3.24 and 2.15 μM, respectively.