HETEROCYCLES

■ Contents

■ Design, Synthesis and Evaluation of Catechol-Based Amyloid Beta Aggregation Inhibitors

Hiroyuki Konno* and Kenta Teruya

*Department of Chemistry and Biological Engineering, Graduate School of Science and Engineering, Yamagata University, Yonezawa, Yamagata 992-8510, Japan

Abstract

The use of small molecules to inhibit amyloid β aggregation is one approach under investigation to prevent the onset of Alzheimer’s disease (AD). One such small molecule is curcumin, but its utility is limited by poor water solubility and hence poor bioavailability. In this review, we summarize the findings of structure-activity relationship studies of curcumin and diaryl γ-dihydropyrone, undertaken to improve their inhibitory effect and physical properties. The key findings are: phenolic hydroxy groups can be introduced at the 2 and 3,4-positions of phenol rings, the C7 spacer of curcumin is essential for good anti-amyloid β aggregation activity; and the catechol moiety is important for both anti-aggregation activity and water solubility. The combination of the C5 spacer unit and mono ketone of curcumin analogues is more effective for water solubility with high anti-amyloid β aggregation activity. Diaryl γ-dihydropyrone with hydroxy groups on phenol rings as cyclocurcumin mimetics also showed anti-amyloid β aggregation activity and high water solubility. Analogues of berberine, a benzylisoquinoline alkaloid also of interest to treat central nervous system diseases, are also reviewed. Finally, we review efforts to develop fluorescent curcumin analogues for use as diagnostic agents.

■ Evaluation of 1,3-Thiazole Derivatives with Pharmaceutical and Chemical Activity: a Review

Sheetal Tresa Fernandes, Jyothi Damodara,* and Smitha Maria DSouza

*Department of Chemistry, St Joseph Engineering College, Mangaluru, India. 

Abstract

1,3-Thiazole is one of the most adaptable scaffolds for heterocyclic compounds. In recent years, thiazole has attracted focus in organic and medicinal chemistry due to its improved effectiveness and significant biological activities. Numerous reviews have reported on the synthesis and pharmacological activities of thiazoles. However, synthesis, pharmaceutical, and chemical applications have not been completely reviewed. The present review focuses on recent work on the synthesis, pharmaceutical and chemical applications of substituted thiazoles. This review discusses the most recent advancements in thiazole-based compounds and emphasizes the importance of design, drug discovery, and the use of thiazole in chemical applications. Additionally, this article is aimed to aid researchers in identifying potential future avenues for the creation of more effective thiazoles.

■ Syntheses of Two New Fluorous Crown Ethers Carrying Sugar Molecules with a Multivalent Bfp Modification: Investigations of Their Partition Ratios in Fluorous Biphasic Systems and Recyclability During Acetoxylation Reaction

Takashi Yamanoi,* Kenji Koike, Taro Koda, and Yoshiki Oda

*Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan

Abstract

This paper describes the design and synthesis of two new fluorous crown ethers (named 1 and 2) carrying sugar molecules modified with multivalent Bfp. Subsequently, we investigated their partition ratios in biphasic systems using FC 72 and several organic solvents. Then, we assessed the activities of 1 or 2 in an FC 72/acetonitrile biphasic system via the acetoxylation reaction using 2-(bromomethyl)naphthalene and potassium acetate, followed by examinations of their recyclability in a two-layer system based on their immobilization in an FC 72 solvent during the acetoxylation reactions.

■ Transnitrosation of Alicyclic N-Nitrosamines Containing Sulfur Atoms in Five- or Six-Membered Rings

Noriko Usui, Masataka Mochizuki, and Keiko Inami*

*Division of Pharmaceutical Organic Chemistry, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Daigakudo-ri 1-1-1, Sanyo-onoda-shi,Yamaguchi, Japan

Abstract

Nitric oxide (NO) is a cell transmitter produced in vivo. Alicyclic N-nitroso compounds serve as potential NO donors in vivo due to the formation of S-nitrosoglutathione by transnitrosation. In this study, N-nitroso compounds with a thioamide group and endocyclic sulfur atoms in 5- or 6-membered rings were synthesized and the transfer of nitroso group was analyzed. All compounds synthesized exhibited transnitrosation activity under acidic condtions. N-Nitroso-1,3-thiazinane-4-carbothioamide exhibited the highest transnitrosation activity.

■ Asymmetric Synthesis of the Unnatural Enantiomer of Codonopsinine and a Stereoisomer via Alkoxyallenes

Morshed Alam Chowdhury and Hans-Ulrich Reissig*

*Institut für Chemie und Biochemie, Freien Universität Berlin, Takustr. 3 Berlin, Germany

Abstract

The unnatural enantiomer of the alkaloid codonopsinine was prepared employing a suitably substituted alkoxyallene equipped with a D-fructose-derived auxiliary. The crucial lithiated 1-alkoxy-3-arylallene was generated in situ from easily available 1,2:4,5-di-O-isopropylidene-3-O-[3-(4-methoxyphenyl)-1,2-dien-1-yl]-β-D-fructopyranose and treated with an N-tosyl imine to afford a diastereomeric mixture of the corresponding allenyl adducts. Their cyclization with silver nitrate in acetonitrile in the presence of potassium carbonate furnished highly substituted 2,5-dihydropyrrole derivatives. After separation, straightforward synthetic operations, with highly diastereoselective hydroborations as key step, provided (+)-codonopsinine (≥95% ee) and one of its stereoisomers.

■ Diterpenoid Alkaloids from Aconitum elliotii Lauener

Ziyu Zhang, Yan Xiao, Peixin Deng, Lin Chen, Shuai Huang, Mengyi Deng, and Xianli Zhou*

*School of Life Science and Engineering, Southwest Jiaotong University, NO.111, North Second Ring Road Chengdu 610031, Sichuan, China

Abstract

Three new diterpenoid alkaloids (1–3), which were named elliotitine A (1), 8-O-ethylindaconitine (2) and 8-O-ethylbikhaconine (3), along with thirty-three known compounds, were isolated from the roots of Aconitum elliotii Lauener. Their structures were elucidated via HR-ESI-MS, 1D and 2D NMR, and X-ray data. Additionally, the anti-inflammation activities of all compounds were evaluated, no compound showed significant anti-inflammatory activity.

■ Biotransformation of Plant Secondary Metabolites by Silkworms

Ryuhei Takeshita, Hiroaki Sasaki, Yasuhiko Matsumoto, Takashi Sugita, and Kaoru Kinoshita*

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

Abstract

Compounds resulting from the biotransformation of plant secondary metabolites by silkworms (Bombyx mori) were found in their feces. SilkMate 2S, an artificial diet, mixed with twelve powdered plant-derived crude drugs was fed to fifth instar silkworms. A glucoside was isolated from the MeOH extract of the feces ejected by the silkworms provided with Scutellariae Radix (Ogon). SilkMate 2S mixed with twelve flavonoids was fed to fifth instar silkworms. Two new compounds, 3-O-β-D-glucopyranosyloxy-6-methoxyflavone (18) and 3-O-β-D-glucopyranosyloxy-4’-hydroxyflavone (19), were obtained from the MeOH extracts of the feces ejected by the silkworms provided with 3-hydroxy-6-methoxyflavone (10) and 3,4’-dihydroxyflavone (11), respectively.

■ (7S)-Macaureas A and B, Two Urea Analogues from the Roots of Lepidium meyenii

Hui-Chun Geng, Shi-Yu Qiu, Shi-Wei Chen, Song-Mei Lu, Fu-Wen Yang, Ji-Rui Wei, Yong-Hui He,* and Min Zhou*

*Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650031, China

Abstract

(7S)-Macaureas A and B (1 and 2), two urea derivatives were isolated from the roots of Lepidium meyenii (Maca) collected from Qujing, Yunnan Province of China. Their structures were established on the basis of extensive spectroscopic data, including 1D NMR, 2D NMR and HRESIMS techniques. The absolute configuration of (−)-1 was corrected as 7S by a concise three-step synthesis from commercially available Boc-L-proline. Macaureas A and B were tested for their cytotoxicities against five human cancer cell lines.