HETEROCYCLES

■ Contents

■ N-Hydroxy- and N-Aminotetrazoles and Their Derivatives – Synthesis and Reactions

Dietrich Moderhack*

*Institute of Pharmaceutical Chemistry, Technical University, Beethovenstrasse 55, D-38106 Braunschweig, Germany

Abstract

This account summarizes the preparative chemistry of the title compounds as it developed from the beginnings a century ago; though detailed, the report is intended to be illustrative rather than encyclopedic.

■ Synthetic Routes towards Pyrimido[1,2-a][1,3,5]triazines (Review)

Anton V. Dolzhenko*

*School of Pharmacy, Curtin University of Technology, GPO Box U1987, Perth, Western Australia 6845, Australia

Abstract

The present review summarizes information on the synthetic approaches to compounds with pyrimido[1,2-a][1,3,5]triazines, 1,3,5-triazino[2,1-b]quinazolines (benzofused pyrimido[1,2-a][1,3,5]triazines), and other polyfused heterocyclic systems bearing these scaffolds. Data concerning potential applications of the pyrimido[1,2-a][1,3,5]triazines, particularly as biologically active agents, are also discussed.

■ A Novel Conjugated Donor-Acceptor System Based on Tetrathiafulvalene Merging Pyrene Unit: Synthesis, Physical Properties and Theoretical Calculations

Chunyang Jia,* Jiaqiang Zhang, Ligong Zhang, and Xiaojun Yao

*State Key Laboratory of Electronic Thin Films and Integrated Devices, School of Microelectronics and Solid-State Electronics, University of Electronic Science and Technology of China, Chengdu 610054, China

Abstract

A novel conjugated donor-acceptor compound (1) based on tetrathiafulvalene has been synthesized and fully characterized. Intramolecular charge transfer (ICT) in compound 1, arising from HOMO-LUMO singlet transitions, has been experimentally evidenced through absorption/fluorescence spectra and theoretical calculations.

■ Synthetic Study of Carbocyclic Core of Cortistatin A, an Anti-Angiogenic Steroidal Alkaloid from Marine Sponge

Naoyuki Kotoku,* Yuji Sumii, Takeshi Hayashi, and Motomasa Kobayashi*

*Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 560-0871, Japan

Abstract

Synthesis of carbocyclic core of cortistatin A (1), a novel anti-angiogenic steroidal alkaloid from Indonesian marine sponge, was investigated. Intramolecular Heck cyclization using substrate 18 achieved construction of 7-membered B-ring structure. The presence of steric hindrance around the reaction center was found to favor endo cyclization pathway in this substrate.

■ Synthesis and Biological Evaluation of a Novel Series of 1,3-Dicoumarinyl-5-aryl-2-pyrazolines

Milan Čačić,* Maja Molnar, and Ivica Strelec

*Department of Applied Chemistry and Ecology, Faculty of Food Technology, J. J. Strossmayer University, Franje Kuhača 20, 31 000 Osijek, Croatia

Abstract

In the present paper novel 1,3,5-trisubstituted 2-pyrazolines (4a-q) were synthesized via condensation of different substituted 3-cinnamoyl-2-oxo-2H-chromenes (2a-q) with 2-(4-methyl-2-oxo-2H-chromen-7- yloxy)acetohydrazide (3). Chalcones were prepared via Claisen-Schmidt condensation by refluxing 3-acetyl-2-oxo-2H-chromen (1) with corresponding aldehydes in ethanol, in the presence of piperidine. All of these compounds were characterized by means of their IR, 1H NMR and LC/MS/MS spectroscopic data and elemental microanalysis. Chalcones and pyrazolines were screened for their antioxidant and iron chelating activity.

■ Reactions and Tautomeric Behavior of 1-(2-Pyridinyl)-1H-pyrazol-5-ols

Peter Pfaffenhuemer, Christian Laggner, Stefan Deibl, Barbara Datterl, and Wolfgang Holzer*

*Department of Drug and Natural Product Synthesis, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria

Abstract

The tautomeric behavior of 1-(2-pyridinyl)-2-pyrazolin-5-one (1a) and its 3-methyl derivative (1b) in different solvents was investigated by means of NMR spectroscopy (1H, 13C, 15N). Moreover, studies regarding the reactions of the title compounds with trimethylsilyldiazomethane, carboxylic acid chlorides, different orthoesters, dimethylformamide diethyl acetal and benzaldehyde are presented. Involvement of pyridine-N atoms in hydrogen bondings was investigated by means of 15N-NMR spectroscopy.

■ Efficient Synthesis of 5-Amino-6-dialkylamino-4-hydroxypentanamide Derivatives for Renin Inhibitors

Yuji Nakamura,* Yasuyuki Ogawa, Chie Suzuki, Teppei Fujimoto, Shojiro Miyazaki, Kazuhiko Tamaki, Takahide Nishi, and Hiroshi Suemune

*Lead Discovery and Optimization Research Laboratories, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan

Abstract

We report an efficient synthetic method for 5-amino-6-dialkylamino-4-hydroxypentanamide derivatives using Shi Asymmetric Epoxidation and the ring opening of N-(2-nitrobenzenesulfonyl)aziridine with hindered secondary amine as key steps.

■ New Furanocoumarins from the Fruits of Melicope triphylla

Ken-ichi Nakashima, Masayoshi Oyama,* Tetsuro Ito, Hiroko Murata, and Munekazu Iinuma

*Laboratory of Pharmacognosy, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan

Abstract

Four new furanocoumarins (1–4) were isolated from the fruits of Melicope triphylla (Rutaceae), together with two known coumarins (5, 6), nine flavonoids (7–15), two alkaloids (16, 17), and methyl p-geranyloxy-trans-cinnamate (18). The structures of the newly identified compounds were determined by extensive 1D- and 2D-NMR spectroscopic analyses to be linear-types of furanocoumarins bearing a hydroxyl or a hydroperoxy group on the geranyloxy side chain.

■ A Novel Pyrrolizidine Alkaloid from Ligularia lankongensis

Aimin Tan,* Mian Zhang, Zhengtao Wang, and Hua Zhang

*Jiangsu Simcere Pharmaceutical R & D Co., Ltd., No. 699-18 Xuanwu Avenue, Xuanwu District, Nanjing 210042, China

Abstract

A novel pyrrolizidine alkaloid named lankongensisine (1) was isolated from the roots of Ligularia lankongensis, and its structure was established by spectroscopic analysis.

■ Reaction of [60]Fullerene with Epoxides under Photo-irradiation: Synthesis of C60-Fused Tetrahydrofuran Derivatives

Chun-Bao Miao,* Zong-Yong Tian, Xiao-Jiao Ruan, Xiao-Qiang Sun, and Hai-Tao Yang*

*School of Petrochemical Engineering, Changzhou University, Changzhou 213164, China

Abstract

The photoreactions of [60]fullerene (C60) with various epoxides have been investigated. Trans 2-aroyl-3-aryloxiranes reacted with [60]fullerene giving both the major cis products and the minor trans adducts. The influence of substituent group on aryl ring on the photoreaction is entirely different from that of preliminary reported thermal reaction. In addition, the photo condition could avoid the decomposition of some original epoxides compared to the thermal condition at high temperature. It provides a simple and efficient route to synthesize C60-fused tetrahydrofuran derivatives.

■ Synthesis and Properties of anti/syn-Regioisomeric Mixtures of Alkyl-Substituted Tetracenes

Chitoshi Kitamura,* Hiroyuki Kano, Hideki Tsukuda, Takeshi Kawase, Takashi Kobayashi, and Hiroyoshi Naito

*Department of Materials Science and Chemistry, Graduate School of Engineering, University of Hyogo, 2167 Shosha, Himeji, Hyogo 671-2201, Japan

Abstract

We prepared anti/syn-regioisomeric mixtures of alkyl-substituted tetracenes via Diels-Alder reaction between asymmetric furans and 2,6-naphthodiyne synthon. The solid-state color of the mixtures changed before and after recrystallization from Et2O, suggesting a difference in the molecular arrangements dependent on the different alkyl substituents as well as the change in the distribution of the anti/syn regioisomers after recrystallization. Slow evaporation of the recrystallized mixtures produced single crystals suitable for X-ray analysis, which revealed that the anti regioisomer was isolated.

■ A Facile Synthesis of New Troponoid-Bearing Flavonoid-Like Compounds

Mingqin Chang, Yang Li, and Wentao Gao*

*Institute of Superfine Chemicals, School of Chemistry and Chemical Engineering, Bohai University, 19 Keji Road, Jinzhou 121000, China

Abstract

A facile synthesis of a series of new flavonoid-like troponoid compounds, namely 3-(3-arylacryloyl)-5-bromotropolones (2a-i) and 2-aryl-6-bromocyclohepta[b]pyran-4,9-diones (3a-i) is described, involving the Claisen-Schmidt condensation reaction of 3-acetyl-5-bromotropolone (1) with various substituted benzaldehydes followed by the intramolecular oxidation cyclization reaction through the treatment with I2/DMSO/H2SO4 system.

■ A Convenient Synthesis of 1,3-Disubstituted 4-Thioxo-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-ones and 4-Thioxo-3,4-dihydropyrido[4,3-d]pyimidin-2(1H)-ones

Kazuhiro Kobayashi,* Toshihide Komatsu, Yuki Yokoi, and Hisatoshi Konishi

*Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

The reaction of 2-chloro-3-lithiopyridine with alkyl isothiocyanates gave the corresponding N-alkyl-2-chloropyridine-3-thiocarboxamides, which in turn were allowed to react with aryl isocyanates in the presence of sodium hydride as a base to give 3-alkyl-1-aryl-4-thioxo-3,4-dihydropyrido[2,3-d]pyrimidin- 2(1H)-ones. A similar sequence starting from 4-chloro-3-lithiopyridine and ethyl isothiocyanate gave 1-aryl-3-ethyl-4-thioxo-3,4-dihydropyrido[4,3-d]pyrimidin- 2(1H)-ones, via 4-chloro-N-ethylpyridine-3-thiocarboxamide.

■ Synthesis of Fluorescence Pyriproxyfen Analogues as Juvenile Hormone Agonists

Hideki Abe, Akimi Sato, Shin-ichi Tokishita, Toshihiro Ohta, and Hisanaka Ito*

*Laboratory of Bioorganic Chemistry, School of Life Sciences, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan

Abstract

Four fluorescence analogues of juvenile hormone agonist pyriproxyfen were designed and synthesized. The synthetic analogue having a dimethylamino group exhibited fluorescence, and therefore can be used for investigation of the mode of action of pyriproxyfen as a juvenile hormone analogue.