HETEROCYCLES

■ Contents

■ Synthetic Approaches to Spiro-oxindoles and Iminoindolines Based on Formation of C2–C3 Bond

Chihiro Tsukano and Yoshiji Takemoto*

*Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-machi, Sakyo-ku, Kyoto 606-8501, Japan

Abstract

Spirooxindole and iminoindoline structures can be found in a wide range of complex natural products, and compounds containing these groups invariably display interesting biological activities. Considering their interesting biological properties and complex architecture, significant research efforts have been directed towards developing new synthetic methods for constructing these structures. This review summarizes our studies towards developing novel synthetic strategies capable of accessing these structures, as well as the applications of these methods to synthesizing natural products, including elacomine and dehaloperophoramidine.

■ Efficient Syntheses of Fluorine-Containing Pyrimido[5,4-c]quinolines and Benzo[h][1,6]naphthyridines by Condensation Reactions of 3-Trifluoro-acetylquinolin-4-amine with Aldehydes and Ketones

Etsuji Okada,* Mizuki Hatakenaka, Shiro Nakano, Takushi Sakaemura, Takashi Mori, and Terukazu Terauchi

*Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan

Abstract

3-Trifluoroacetylquinolin-4-amine reacted easily with various aldehydes in the presence of aqueous ammonia to afford mainly trifluoromethylated pyrimido[5,4-c]quinoline derivatives in moderate to high yields. In contrast, the use of ketones instead of aldehydes under almost the same conditions, mostly gave benzo[h][1,6]naphthyridine derivatives in excellent combined yields.

■ Synthesis and Antimicrobial Evaluation of Some New Dihydropyridine, Pyrazole, Chromene, Pyrrole, Thiazole and Thiophene Derivatives

Ahmed A. Fadda,* Hala M. Refat, Khaled S. Mohamed, and Nada A. H. Mohamed

*Department of Chemistry, Faculty of Science, University of Mansoura, Mansoura 35516, Egypt

Abstract

Synthesis of 2-cyano-N-((2-methoxynaphthalen-1-yl)methylene)- acetohydrazide (3) and its use as a key intermediate for the synthesis of some new heterocyclic compounds such as dihydropyridines (4, 6 and 8), pyrazoles (9 and 10), chromene (11), pyrroles (12 and 13), thiazoles (14 and 17) and thiophene (18-20) derivatives were described. The structures of newly synthesized compounds have been established on the basis of their IR, 1H-NMR, 13C-NMR and mass spectral data and have been screened for their antimicrobial activity.

■ Fluorinated β-Diketo Phosphorus Ylides: Their Cyclocondensation with Amidines Affording 4-Trifluoromethyl- and 4-Perfluoroalkyl-Substituted Pyrimidines

Ryosuke Saijo, Genki Watanabe, Ken-ichi Kurihara, and Masami Kawase*

*Faculty of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan

Abstract

A study is presented for the syntheses of a series of 4-trifluoromethyl- and 4-perfluoroalkyl-substituted pyrimidines from the reaction of trifluoromethyl or perfluoroalkyl β-diketo phosphorus ylides (Ph3P=C(CORF)COR) with amidine hydrochloride.

■ Stepwise Syntheses of 3,6-Carbazole-Based Conjugated Oligomers

Hiroyuki Fujita and Tsuyoshi Michinobu*

*Department of Organic and Polymeric Materials, Graduate School of Science and Technology, Tokyo Institute of Technology, O-okayama 2-12-1, Muguro-ku, Tokyo 152-8552, Japan

Abstract

A series of monodispersed ethynylene-linked 3,6-carbazole oligomers was synthesized by the Sonogashira coupling and deprotection protocol. The resulting conjugated carbazole oligomers were characterized by 1H-, 13C-NMR, and IR spectroscopies, and MALDI-TOF mass spectrometry. The effective conjugation length of the 3,6-carbazole structure was evaluated from the longest wavelength absorption maxima (λmax) in CH2Cl2. The λmax gradually red-shifted with the increasing carbazole unit, and this bathochromic shift saturated at the pentamer.

■ Syntheses of Acridines and Quinazoline-2,4(1H,3H)-dithiones by Rearrangements of N-Heterocyclic Carbenes of Indazole

Zong Guan, Mimoza Gjikaj, and Andreas Schmidt*

*Institute of Organic Chemistry, Clausthal University of Technology, Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld, Germany

Abstract

N-Heterocyclic carbenes of indazole which are arylated at N1 (1-aryl-indazol-3-ylidenes) have been generated by deprotonation of the corresponding indazolium salts. On deprotonation with potassium carbonate, potassium phosphate or tert-butanolate in dioxane or toluene at reflux temperature, a rearrangement to acridines took place. Deprotonation with n-butyllithium in THF at room temperature in the presence of carbon disulfide gave quinazoline-2,4(1H,3H)-dithiones by a new rearrangement reaction.

■ Isocoumarins from the Bark of Lindera caudata

Yan-Qing Ye, Cong-Fang Xia, Juan-Xia Yang, Yu-Chun Yang, Xue-Mei Gao, Gang Du, Hai-Ying Yang, Yin-Ke Li, and Qiu-Fen Hu*

*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

Three new isocoumarins, caudacoumarins A - C (1 - 3), together with two known isocoumarins (4 - 5) were isolated from the bark of Lindera caudata. Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D- NMR techniques. Compounds 1 - 5 showed modest anti-tobacco mosaic virus (anti-TMV) activity with inhibition rate of 14.8 - 24.5%, respectively.

■ Cytotoxicity Flavones from Desmodium oxyphyllum

Xue-Mei Gao, Huang Wang, Yin-Ke Li, Bing-Kun Ji, Cong-Fang Xia, Juan-Xia Yang, Ming Zhou, Yan-Qing Ye, and Qiu-Fen Hu*

*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 flavones, oxyphyllumflavone A and B (1 and 2) were isolated from Desmodium oxyphyllum. Their structures were elucidated by spectroscopic methods including extensive 1D- and 2D-NMR techniques. Compounds 1 and 2 are the first naturally occurring flavones possessing a six-membered 6-methyl-α-pyrone ring. Compounds 1 and 2 were also evaluated for their cytotoxicity against NB4, A549, SHSY5Y, PC3, and MCF7 cell lines, and they showed cytotoxicity with IC50 values in the range of 4.2 – 9.6 μM.

■ Synthesis of Novel β-Lactam Hybrids of Phenstatin and Other Substituted Aromatics as New Bioactives

David P. Brown,* Haoran Zhao, Julkernine M. Khondoker, Jatin R. Bhavsar, and Cecil C. Sigamoney

*Department of Chemistry, St. John's University, 8000 Utopia Parkway, Jamaica, New York 11439, U.S.A.

Abstract

Novel β-lactam hybrids have been synthesized as new chemical entities in the development of new antibiotic antineoplastic agents.