HETEROCYCLES

■ Contents

■ Functionalization of Benzylic sp3 C-H of 2-Methylazaarenes in Deep Eutectic Solvent

Guo-Qing Chen, Zong-Bo Xie,* Feng Ai, Zhong-Sheng Chen, Jin Lan, Zhi-Yu Hu, and Zhang-Gao Le*

*Department of Applied Chemistry, East China University of Technology, Guanglan Road 330013, China

Abstract

The catalyst-free addition of 2-methylazaarene benzylic sp3 C-H to electron-deficient olefins in deep eutectic solvents is reported. Moderate to good yields were obtained in 2 h at 80 °C in deep eutectic solvents. The method was operationally easy and involved mild reaction conditions. This expands the application of deep eutectic solvent in sp3 C-H functionalization reaction.

■ A Facile Synthesis, Docking Study and Antitumor Activity of Some Furan-Chalcone and Furylpyrazole Hybrids

Ahmed S. Radwan*

*Chemistry, Taif University, Taif 21995, Saudi Arabia

Abstract

Several new furan-based heterocycles were prepared by the reaction of furan-chalcone derivative 1 and/or furylpyrazole thioamide derivative 2 with various electrophilic reagents (e.g. 4-anisaldehyde, thiosemicarbazide, dimethylformamide dimethyl acetal, phenyl isothiocyanate, N-cyanoacetyl-pyrazole and nitrous acid). Spectroscopic and elemental analyses were applied to emphasize the structures of these furan containing scaffolds. The newly constructed furan-chalcones and furylpyrazoles were tested for their cytotoxicity on hepatocellular cancer (HepG-2), breast cancer (MCF-7) and colon cancer (HCT-116). The pyrazole scaffold 10 exhibited the highest cytotoxic effect against the tested cell lines HepG2 (IC50 7.36±0.6 μg/mL), HTC-116 (IC50 8.14±0.8 μg/mL), and MCF-7 (IC50 12.16±0.8 μg/mL), compared with the standard anticancer drug Doxorubicin (DOX). Binding mode of the most active compound 10 was illustrated using docking methods that were processed in the same co-crystallographic inhibitor binding site, docking was revealed same interaction of compound 10 analogous to the binding of native inhibitor.

■ Direct Determination of the Absolute Configurations of Chiral Cyanohydrins Using Bis(zinc porphyrin) as a CD-Sensitive Bidentate Host

Satoshi Hayashi, Shiori Takeda, Masahiro Noji,* and Toshikatsu Takanami*

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

Abstract

The absolute configurations of cyanohydrins are readily determined via an exciton-coupled circular dichroism (ECCD) protocol using bidentate bis(zinc porphyrin) host molecule BP1 as a CD-sensitive chirality probe. UV–vis and NMR studies revealed a monodentate binding mode of cyanohydrin with BP1. Based on these studies, a simple working model using a Newman projection of cyanohydrins was established, allowing BP1 to determine the stereochemistry of various cyanohydrins in a non-empirical and unambiguous manner.

■ A New Iridoid Glucoside from Anisacanthus virgularis and Its Antiamoebic Activity

Mohamed S. Refaey,* Reda A. Abdelhamid, Mohamed A. A. Orabi, Ahmed A. Ali, Reda Fouad Ahmed Abdelhameed, Eman A. A. Mousa, Shinjiro Hamano, and Koji Yamada

*Department of Pharmacognosy, University of Sadat City, Sadat City, Menofia 32897, Egypt

Abstract

Phytochemical investigation of Anisacanthus virgularis aerial parts resulted in isolation of a new iridoid glucoside named as 7-O-p-trans-coumaroyl caryoptoside (1) together with two known iridoids, caryoptoside (2) and lamalbide (3). Their structures were elucidated by spectroscopic methods including 1D and 2D-NMR techniques. The isolated compounds together with the MeOH and aqueous extracts of the plant were investigated for their antiamoebic activity in vitro. The micro dilution technique was employed to investigate antiamoebic activity against Entamoeba histolytica HM1-SS strain. The results showed that the MeOH extract had good inhibition along 72 hours followed by the aqueous extract at concentration of 15 mg/mL. The compounds 1-3 showed good inhibition growth percent 72.2%, 50.1% and 52.6% after 24 hours of incubation at a concentration of 4 μM, respectively compared to the standard antiamoebic drug, Metronidazole.

■ Trifunctionalized Allenes. Part VI. Synthesis of 2,5-Dihydro-1,2-oxaphospholes, Furan-2(5H)-ones and 5,6-Dihydro-2H-pyrans by Electrophilic Cyclization and Cycloisomerization of 4-Phosphorylated 6-Hydroxyhepta-2,3-dienoates

Ismail E. Ismailov, Ivaylo K. Ivanov, and Valerij Ch. Christov*

*Department of Chemistry, Faculty of Natural Sciences, Konstantin Preslavsky University of Shumen, 115, Universitetska str. BG-9712 Shumen, Bulgaria

Abstract

We have synthesized model compounds of three types heterocyclic compounds by electrophilic cyclization and cycloisomerization of 4-phosphorylated 6-hydroxyhepta-2,3-dienoates. Reactions with electrophiles produce mixtures of the 2,5-dihydro-1,2-oxaphosphole-5-carboxylates and the 5-phosphorylfuran-2(5H)-ones by competitive electrophilic cyclization due to the neighboring phosphonate (phosphine oxide) and the carboxylate groups participation. Starting compounds were smoothly converted into the corresponding 4-phosphoryl-5,6-dihydro-2H-pyran-2-carboxylates, by using 5 mol% of a silver salt as a catalyst in the 6-endo-trig cycloisomerization reaction.

■ A Comparison between KBH4 and NaBH4 in Their Reduction of Pyridinium Salts

Hao Quan, Bin Zhu, Xiaolin Li, Li Zhan, and Yu Luo*

*Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, China

Abstract

This paper compares potassium borohydride and sodium borohydride in the reduction of pyridinium salts to tetrahydropyridines. The results indicate that potassium borohydride is more suitable for this reaction with low costs, mild reaction conditions and improved yields.

■ A New γ-Butenolide Glycoside from the Root of Styphnolobium japonicum

Takahiro Utsumi, Ryuichiro Suzuki,* Hitoshi Kamauchi, Sae Misawa, Masashi Kitamura, Yoshiaki Sugita, and Yoshiaki Shirataki

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

Abstract

A new γ-butenolide glycoside, named styphonoloside A (1), was isolated from the root of Styphonolobium japonicum (L.) Schott (= Sophora japonica L.), together with saikoisoflavonoside A (2) and sophoraside A (3). The structure of 1 was characterized as puerol B 2”-O-neohesperidoside based on one- and two-dimensional (1D and 2D) NMR, MS, and electronic circular dichroism (ECD) spectral data. The absolute configuration of the aglycone moiety of 1 was assigned by comparing its experimental ECD spectrum with the calculated ECD spectrum.

■ Electrooxidation of Chlorodiphenylphosphine under Ammonia Atmosphere. Synthesis of 2,2,4,4,6,6-Hexaphenylcyclotriphosphazene and Iminobis(aminodiphenylphosphorus) Chloride

Manabu Kuroboshi,* Yasunari Masumoto, and Hideo Tanaka

*Division of Chemsitry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Okayama 700-8530, Japan

Abstract

Electrooxidation of MeCN solution of chlorodiphenylphosphine in the presence of Cl‒ under NH3 atmosphere gave a mixture of 2,2,4,4,6,6-hexaphenylcyclotriphosphazene and iminobis(aminodiphenyl- phosphorus) chloride.

■ First Synthesis of Benzo[e][1,3,2]Diazaphosphinino[1,6-c] [1,3,2]Oxazaphosphinines

Tarik E. Ali,* Mohammed A. Assiri, and Ibrahim S. Yahia

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

Abstract

A series of novel benzo[e][1,3,2]diazaphosphinino[1,6-c][1,3,2]-oxazaphosphinine derivatives (3a-f) were synthesized by cyclization reactions of 6-(2-hydroxyphenyl)-2-phenyl-1H-2-oxido-1,3,2-diazaphosphinine (2) with some phosphorus dichlorides in the presence of triethylamine in dry dioxane under reflux. The structures of all the synthesized compounds were established by IR, 1H-, 13C- and 31P-NMR spectra as well as by elemental analysis and mass spectral analysis.