HETEROCYCLES

■ Contents

■ Alkyl Pyridinesulfonates and Allylic Pyridinecarboxylates, New Boosters for the Substitution at Secondary Carbons

Yuichi Kobayashi*

*Meiji University, Organization for the Strategic Coordination of Research and Intellectual Properties, 1-1-1, Higashimita, Tama-ku, Kawasaki, Kanagawa, 214-8571, Japan

Abstract

Substitution at allylic secondary carbons using the pyridinecarboxylate (picolinoxy, PyCO2, or Pic) leaving group is described in the first part of this review (Sections 2–4). Alkyl as well as less reactive alkenyl, heteroaryl, and aryl copper reagents are suitable for the substitution, giving anti SN2' products highly regio- and stereoselectively. In Section 2, finding and synthetic application of the allylic substitution giving tertiary carbon centers are presented. Extension of the substitution for the construction of quaternary carbon centers is described in Section 3 with its synthetic application. Section 4 deals with the construction of quaternary carbon centers on cyclohexane rings by the allylic substitution of cyclohexylidene picolinates. The stereochemistry is created by equatorial attack to the chair conformer with high diastereselectivity. The stereochemical prediction facilitated synthesis designs of biologically active compounds. The second part of the review (Section 5) presents recent advances in metal-catalyzed substitutions at secondary alkyl carbons, giving enantiomerically enriched products. Our findings of the pyridinesulfonyloxy leaving group and an associated copper catalyst are included. Substitutions with cuprates are mentioned briefly for reactivity discussion with the copper-catalyzed substitution.

■ Bis(1,3-dimethylimidazolidinone) Hydrotribromide (DITB) Promoted Multicomponent Reaction for the Synthesis of Highly Functionalized Piperidines

Shiqiang Yan, Shuwang He, Shuying Li, Zhiqiang Hu,* and Wei Zhang*

*School of Pharmacy, Fudan University, Shanghai 201203, China

Abstract

A convenient and efficient method has been developed for the synthesis of highly functionalized piperidines via three-component, one-pot domino reaction of β-ketoesters, aromatic aldehydes, and anilines in the presence of catalytic amount of bis(1,3-dimethylimidazolidinone) hydrotribromide (DITB) in ethanol at room temperature.

■ Absolute Configuration of the Butenolide of Abietane

Min Li, Xu Li, Ian D. Williams, Herman H-Y. Sung, Zhi-Da Min, and Qiong Zhang*

*Department of Pharmaceutical Science, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi Province 030001, China

Abstract

17-Hydroxyjolkinolide A-B (1-2) and jolkinolide A-B (3-4) are four ent-13(15)-abietane-16,12-olide type diterpenoids isolated from the roots of Euphorbia fischeriana Steud. The absolute configurations of 1 and 2 were established by X-ray crystallographic analysis of their mono-bromobenzoate derivatives. On basis of our research, the absolute configuration of the butenolide of abietane can be determined by ECD spectra. The potential antituberculosis effects of these diterpenoids were evaluated using a Mycobacterium smegmatis model. The most potent compound according to the in vitro bioassay used was 17-hydroxyjolkinolide B (2) (MIC 1.8 μg/mL).

■ Identification and Quantification of Alkaloid Compounds from Different Parts and Production Areas of Datura metel L.

Yang Shi Hui, Liu Yan, Wang Qi, Sun Yan Ping, Guan Wei, Liu Yuan, Yang Bing You,* and Kuang Hai Xue*

*Key Laboratory of Chinese Materia, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China

Abstract

An ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) method was used to identify alkaloids in six parts of Datura metel L. (D. metel L.). 65 Alkaloids were tentatively identified. Meanwhile, a rapid, sensitive and reliable ultra-high-performance liquid chromatography tandem triple quadrupole mass spectrometry (UPLC-Q-TRAP-MS/MS) technique had developed to determine the contents of 22 alkaloids in five minutes, with good precision and repeatability. This method provided a feasible solution for the content determination of alkaloid in D. metel L.

■ Ag(I)/sec-Amine-Amidphos-Catalyzed endo-Stereoselective Synthesis of Fully Substituted Pyrrolidines via 1,3-Dipolar Cycloaddition Based on Azomethine Ylides

Haifei Wang, Chen Zhang, Jialin Liu, Xinluo Song, and Haiyun Jiang*

*College of Packaging and Materials Engineering, Hunan University of Technology, Zhuzhou 412007, China

Abstract

Cooperative catalysis using multifunctional organic scaffolds in combination with transition-metal ions is emerging as a powerful tool in asymmetric synthesis. In this report, a series of multifunctional amidophosphanes derived from substituted 1,2-benzenediamine or 2-aminobenzylamine and chiral α-amino acids, in combination with silver(I) salts, have been developed to cooperatively catalyze the azomethine ylides-involved 1,3-dipolar cycloaddition with maleates. Under optimal conditions, fully substituted endo-pyrrolidines were obtained in high to excellent yields (up to 92% yield) and enantioselectivities (up to 94% ee).

■ Lactamization of Alkenyl C-H Bonds to Generate 2-Quinolinones with Triphosgene

Zhen Zhang,* Zixiao Wang, and Guizhi Du*

*Key Laboratory of Coarse Cereal Processing (Ministry of Agriculture and Rural Affairs), Chengdu University, Chengluo Road 2025, Chengdu, Sichuan 610041, China

Abstract

A simple and easy-going method is developed to synthesize the analogues of 2-quinolinones by using triphosgene (BTC) as the carbonyl source. In these reactions, both the toxic carbon monoxide (CO) and phosgene are avoided and the 2-quinolinones are obtained in moderate to good yields under mild conditions, all of which are anticipated to be meaningful in both industry and laboratory.

■ The Synthesis and Glycosidase Inhibitory Activity of Analogues of Tiruchanduramine

Zackary J. R. Ashworth, Barbara Bartholomew, Daniel M. Evans, Josephine Forde-Thomas, Karl F. Hoffmann, Reece Murdoch, Robert J. Nash, Hazel Sharp, Helen Whiteland, and Patrick J. Murphy*

*School of Natural Sciences, Bangor University, Gwynedd, LL57 2UW, UK

Abstract

Five analogues (7a-e) of the metabolite tiruchanduramine 1 were prepared. Compounds 7d and 7e were specific inhibitors of yeast α-glucosidase, whilst 7e specifically inhibited Bacillus α-glucosidase. Compounds 7b and 7c were the best inhibitors of β-glucosidase. All 5 compounds inhibited β-galactosidase, but once again 7e was the best inhibitor. It was apparent that different chain lengths in the compounds 7a-e affect the degree of inhibition. Some of the synthetic analogues show significantly improved inhibition of α-glucosidases when compared to tiruchanduramine 1 and also improved specificity.

■ Novel Ring Transformation of Uracils to 2-Oxazolidinones

Yoshiaki Kitamura,* Yuki Nagaya, Yuto Ohshima, Daiki Kato, Asuki Ohguchi, Hiroshi Katagiri, Masato Ikeda, and Yukio Kitade

*Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University , 1-1 Yanagido, Gifu, Gifu 501-1193, Japan

Abstract

Treatment of N3-electron-withdrawing group-protected uracil derivatives bearing a 2-hydroxyethyl moiety at the 1-position with base under anhydrous conditions affords the corresponding 2-oxazolidinone by opening the pyrimidine ring between C2 and N3, followed by ring closure between C2 and the neighbouring hydroxy group. This ring transformation is applicable to various uracil analogues to obtain the desired 2-oxazolidinone in moderate to excellent yield.

■ Synthesis and Fluorescence of 9-Benzyl-9H-carbazole Derivatives and Its Application for Recognition of Rare Earth Cations

Yu-Ying Du, Li-Min Han,* Liang-Wu Guo, Zhi-Chao She, Jing Cui, Li Lv, and Ruo-Xuan Gao

*Department of Chemical Engineering, Inner Mongolia University of Technology, Huhhot 010051, PR China

Abstract

The synthesis and photophysical properties of 9-benzyl-9H-carbazole derivatives have been investigated. A novel ethyl 9-benzyl-1-methyl-9H-carbazole-2-carboxylate (Bncz 1) fluorescent chemosensor has been developed to recognize Ce(III) through a significant increase in fluorescence intensity in ethanol, whereas there is minimal difference on the introduction of the other rare earth metal cations (Yb3+, Sm3+, Gd3+, Er3+, Pr3+, Eu3+, Tb3+, Tm3+, Dy3+, Ho3+, Nd3+, Lu3+, Y3+, Sc3+, La3+). A moderate association constant of K= 2.419 × 105 L·mol−1 has been determined by fluorescence titration, and the corresponding Job’s plot analysis indicated 1:1 binding for metal complex formation. The linear increase in fluorescence intensity in response to different concentrations of Ce3+ gives a low limit of detection of 7.269 × 10-6 M. 9-Benzyl-9H-carbazole derivative probe has a great potential for the detection of rare earth metal cations.

■ Antifungal Compound against Azole-Resistant Candida albicans from a Marine-Derived Fungus, Paraboeremia selaginellae

Eri Yamaguchi, Kazuha Okabe, Hitoshi Kamauchi, Sanae Kurakado, Takashi Sugita, Kaoru Kinoshita,* and Kiyotaka Koyama*

*Department of Pharmacognosy and Phytochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

A new compound (1) and AB4063-A (2), whose stereochemistry was unstated, were isolated from the marine-derived fungus Paraboeremia selaginellae. The structure of 1 was elucidated from spectroscopic data (NMR, MS, IR), and the absolute configuration of the N-methylvaline moiety was determined. Compound 2 showed antifungal activity against azole-resistant Candida albicans.