HETEROCYCLES

■ Contents

■ Chiral Oxazolidine Catalyst for Asymmetric Synthesis

Hiroto Nakano,* Yuko Okuyama, and Eunsang Kwon

*Department of Applied Chemistry, Graduate School of Engineering, Muroran Institute of Technology, 27-1 Mizumoto, Muroran, Hokkaido 050-8585, Japan

Abstract

A design of a chiral ligand and its metal-coordinated catalyst is very important for achievement of a highly optical purity and a chemical yield in an asymmetric reaction. Recently, we developed the chiral oxazolidine ligands having N,O acetal structure, such as phosphinooxazolidine (POZ), phosphinooxazinane (POZI) and oxazolidine (OZ). POZ and POZI afforded products in an excellent enantioselectivities in Pd-catalyzed asymmetric allylic alkylation and tandem allylation. Furthermore, cationic Pd-POZ catalysts showed high levels of catalytic activity in the asymmetric Diels-Alder (DA) reactions of some dienes with oxazolidinone or pyrrazolidinone typed dienophiles. Cationic Pd-POZ catalyst showed an excellent catalytic activity in the DA reaction in ionic liquid (IL). The catalyst could be reused eight times without significant decrease of yield and enantioselectivity in the use of an ionic liquid as a solvent. OZ ligand also worked as organocatalyst in the DA reaction of 1,2-dihydropyridies with acroleins to afford the useful intermediate of Tamiflu. The review summarizes these our studies.

■ A CU[I] CATALYZED MILD AND GENERAL SYNTHESIS OF 1,4-DISUBSTITUTED-1,2,3-TRIAZOLES FROM TERMINAL ACETYLENES AND IN SITU GENERATED ALKYL AZIDES

José Emilio de la Cerda-Pedro, Yoarhy Alejandro Amador-Sánchez, Mayra Cortés-Hernández, Jovana Pérez-Pérez, Susana Rojas-Lima,* and Heraclio López-Ruiz*

*Chemistry Academic Area (AAQ), Autonomous University of Hidalog (UAEH), University City, Pachuca-Tulancingo Road Km 4.5, Mineral de la Reforma, Hidalogo, CP 42184, Mexico

Abstract

Cuprous cyanide, generated in situ from cupric sulfate and sodium cyanide, catalyzes the synthesis of 1,4-disubstituted-1,2,3-triazoles from in situ generated alkyl azides and mono-substituted alkynes in a one pot room temperature process.

■ Effective Method of Lipase-Catalyzed Enantioresolution of 6-Alkylsulfanyl-1,4-dihydropyridines

Zigmars Andzans,* Ilze Adlere, Aleksandrs Versilovskis, Laura Krasnova, Signe Grinberga, Gunars Duburs, and Aivars Krauze

*Dept. Organic Chemistry, Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia

Abstract

A series of 6-alkylsulfanyl-1,4-dihydropyridines (±)2 bearing a methoxycarbonylethyl group as a mild easily removable protecting group at S atom have been prepared by alkylation of 6-thioxo-1,4-dihydropyridines 1 with methyl bromopropionate. Candida antarctica lipase B (Novozym 435®, CAL-B) - and Amano Acylase (Aspergillus mellus)-catalyzed kinetic resolution has been investigated in water-saturated diisopropylether (IPE) at 25 and 45 oC. Further deacrylation and alkylation of enantioenriched 1,4-dihydropyridine-6-thiolates (-)4 and (+)4 gave rise to optically active 1,4-dihydropyridines (-)2, (+)2, (-)5 and (+)5 in 85-99% enantiomeric excess. The experiments present the 6-(methoxycarbonylethyl)sulfanyl group as an essentially new enzymatically labile (activating) group. The ester group being 6 bonds remote from the chiral center undergoes easy enzymatic hydrolysis and could be used for kinetic resolution of racemic 1,4-DHPs. This developed method offers access to mild optically active nucleophilic tiolates, which could be easily derivatized with electrophilic reagents.

■ Regioselectivity of the Palladium-Mediated Intramolecular Coupling Reaction of Highly Oxygenated Phenyl Benzoate Derivatives and Application to the Synthesis of Altertenuol

Takuya Matsukihira, Shumpei Saga, Yoshikazu Horino, and Hitoshi Abe*

*Department of Environmental Applied Chemistry, Faculty of Engineering, Toyama University, Gofuku 3190, Toyama 930-8555, Japan

Abstract

The regioselectivity of the intramolecular biaryl coupling reaction of 3’,4’-dialkoxyphenyl 2,4-dimethoxybenzoates was investigated using a palladium reagent, and transition state models of the reaction are proposed. As an application of this study, a short-step synthesis of altertenuol is also performed.

■ Ferrier Glycosylation Reaction Catalyzed by Bi(OTf)3-Montmorillonite K-10: Efficient Synthesis of 3,4-Unsaturated Sialic Acid Derivatives: Synthesis and Biological Evaluation as Inhibitors of Human Parainfluenza Virus Type 1

Mai Oba, Yayoi Ueno, Satoru Kitani, Takuya Hayakawa, Tadanobu Takahashi, Takashi Suzuki, Masayuki Sato, and Kiyoshi Ikeda*

*Department of Pharmaceutical Sciences, Hiroshima International University, 5-1-1, Hirokoshingai, Kure, Hiroshima, 737-0112, Japan

Abstract

The reaction of the 4,5-oxazoline derivative of sialic acid with various alcohols was effectively promoted by a catalytic amount of montmorillonite K-10 clay-supported Bi(OTf)3 to produce a variety of 3,4-unsaturated sialic acids via the Ferrier glycosylation reaction in moderate yields. The deprotection of the isopropylidene group and hydrolysis of the ester group of 7a-g gave 4a-f, whose inhibitory activities against hPIV-1 sialidase were studied.

■ Radical Cyclization and 1,5-Hydrogen Transfer in Selected Aromatic Diazonium Salts

Benedetta Maggio, Gianfranco Fontana, Demetrio Raffa, Francesco Ferrante, and Giuseppe Daidone*

*STEBICEF, University of Palermo, Via Archirafi 32, 90123 Palermo, Italy

Abstract

2-(Methyl-(3-methyl-1-phenyl-1H-pyrazol-5-yl)carbamoyl)thiophene- 3-diazonium hydrogen sulfate 20, 2-(methyl-(3-methylisoxazol-5-yl)carbamoyl)benzenediazonium hydrogen sulfate 21 and 2-(methyl(phenyl)carbamoyl)benzenediazonium hydrogen sulphate 22 were synthesized and reacted with a CuSO4/NaCl/ascorbic acid combination to give complex mixtures. The structures of the reaction products were elucidated, depending upon the pathways followed. Compound 20 almost exclusively afforded an Ar-5 cyclization product and trace amounts of the product derived from a competing Ar-6 Pschorr closure. In the case of compound 21, the Ar-6 cyclization was not observed, while the Ar-5 cyclization and 1,5-hydrogen radical transfer processes equally occurred. Finally, the Ar-6 cyclization was observed as the main process for compound 22, accompanied by the Ar-5 cyclization and, in a much lesser extent, by an 1,5-hydrogen radical transfer process.

■ One-Pot Synthesis of 3,5-Diphenyl-1H-pyrazoles from Chalcones and Hydrazine under Mechanochemical Ball Milling

Ze Zhang,* Ya-Jun Tan, Chun-Shan Wang, and Hao-Hao Wu

*School of Biological & Chemical Engineering, Anhyui Polytechnic University, No. 8, Beijing Road, Wuhu 241000, China

Abstract

A highly efficient and environmentally friendly method has been developed for facile synthesis of 3,5-diphenyl-1H-pyrazoles under mechanochemical ball-milling conditions. The advantages of short reaction time, high efficiency, no separation of in situ generated intermediate, using cheap sodium persulfate as the oxidant, together with very simple work-up procedure, make this one-pot and solvent-free protocol a green and powerful alternative to traditional methods for the synthesis of these kinds of compounds.

■ Synthesis of Novel Benzimidazole and Benzothiazole Derivatives

Ahmed F. Darweesh, Ahmed E. M. Mekky, Amani A. Salman, and Ahmad M. Farag*

*Department of Chemistry, Faculty of Science, Cairo University, Giza 12013, Egypt

Abstract

1-(Benzothiazol-2-yl)-2-phenylsulfonyl-1-ethanone (1) and 1-(1-methyl-1H-benzimidazol-2-yl)-2-(phenylsulfonyl)-1-ethanone (2) were used as potential scaffolds for biologically interesting azoloazine derivatives via their reaction with the diazonium salts of 5-aminopyrazole, 5-amino[1,2,4]triazole and 2-aminobenzimidazole. Coupling of the β-ketosulfones 1 or 2 with diazotized aromatic amines afforded the corresponding arylhydrazone derivatives which have been utilized as versatile building blocks for the synthesis of biologically interesting pyridazine ring systems.

■ Synthesis and Cyclization of a Proposed Biosynthetic Epoxy Intermediate of a Marine Monocyclic Ether Amide, Brevisamide

Tomohiro Shirai, Yuki Takimoto, Takefumi Kuranaga, Kazuo Tachibana, Masayuki Satake,* Daniel G. Baden, and Jeffrey L. C. Wright

*Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Abstract

Proposed biosynthetic intermediates of a marine monocyclic ether alkaloid, brevisamide (1) were synthesized for biosynthetic studies on the marine ladder-frame polyethers. The intermediates comprising a linear backbone with trans-olefin (2) and epoxide (3) functionality were synthesized via a Suzuki–Miyaura cross coupling reaction and a Katsuki–Sharpless asymmetric epoxidation reaction. In protic solvents, 3 was unstable and readily cyclized to an unnatural 5-membered ether ring compound (4).

■ Preparation of Cyclic β-Amino Acid Derivatives with Quaternary Carbon Center via a Radical Addition-Cyclization Sequence

Norihiko Takeda, Masafumi Ueda, Seiko Kajisa, Kenji Matsuno, Takeaki Naito, and Okiko Miyata*

*Department of Medicinal Chemistry, Kobe Pharmaceutical University, 4-19-1, Motoyamakitamachi, Higashinada, Kobe 658-8558, Japan

Abstract

A new method has been developed for the construction of α,α-disubstituted cyclic β-amino acid derivatives via the sulfanyl radical addition-cyclization reaction of oxime ether connected with acrylate. This reaction proceeded smoothly to give the cyclized products that contained a quaternary carbon center. Furthermore, the use of carbon centered radicals in the reaction allowed for the formation of cyclic amines containing various alkyl chains. The cyclized product with a quaternary carbon center could also be converted to sterically congested cyclic β-amino acid.

■ Microwave-Irradiated Synthesis of 1,2-Dihydropyridines from N-Functionalized Enaminones and Enals through Domino Condensation and 6π-Azaelectrocyclization

Elkhabiry Shaban, Md. Imran Hossain, Ming-Yu Wu, Yoshihiko Takemasa, Sachie Nagae, Wei Peng, Hiroyuki Kawafuchi, and Tsutomu Inokuchi*

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

Abstract

N-Amino-substituted 1,2-dihydropyridine motifs are constructed using cyclohexane-1,3-diones via the Knoevenagel condensation with enals followed by 6π-electrocyclization using ethylenediammonium diacetate as a catalyst under MW irradiation. A survey of substituents on the N atom indicated that the phenylamino and benzoylamino groups are favorable for the reaction, while phenyl, benzyl, and no-substituent are not. The substituent at C2 of enals is crucial for smooth formation of the corresponding adducts and slightly higher yields are obtained with enals bearing an electron-withdrawing aromatic at C3.

■ Chromone Derivatives from the Leaves of Nicotiana tabacum and Their Anti-Tobacco Mosaic Virus Activities

Guangyu Yang, Wei Zhao, Tao Zhang, Yuanxing Duan, Zhihua Liu, Mingming Miao, and Yongkuan Chen*

*Key Laboratory of Tobacco Chemistry of Yunnan Province, Yunnan Academy of Tobacco Science, Kunming 650106, China

Abstract

Two new chromone derivatives, 5-hydroxy-9-methyl-1-(2-oxopropyl)benzo[β]oxepin-7(2H)-one (1), 5-hydroxy-2-methoxy-9-methyl-1-(2-oxopropyl)benzo[β]oxepin-7(2H)-one (2), together with five known chromone derivatives (3-7), were isolated from the leaves of Nicotiana tabacum. Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D-NMR techniques. Compounds 1-7 were tested for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that compound 2 showed high anti-TMV activity with inhibition rate of 31.5%. It inhibition rate is high than that of positive control. The other compounds also showed potential anti-TMV activities with inhibition rates in the range of 11.2 – 23.5%, respectively.

■ Novel Cytotoxic Metabolites from the Marine-Derived Fungus Trichoderma citrinoviride

Xiao Hu, Mei-Wei Gong, Wei-Wei Zhang, Qiu-Hong Zheng, Qin-Ying Liu, Li Chen,* and Qi-Qing Zhang*

*College of Chemistry and Chemical Engineering, Institute of Biomedical and Pharmaceutical Technology , Fuzhou University, No. 523, Gongye Road, Fuzhou City, 350002, China

Abstract

Three new compounds, trichoderiol C (1), citrinoviric acid (4), and penicillenol D (5), together with seven known compounds, trichoderiol A (2), lignoren (3), penicillenol B1 (6), penicillenol B2 (7), cyclo-(Leu-Pro) (8), cyclo-(Ile-Pro) (9), and cyclo-(Phe-Pro) (10), were isolated from the marine-derived fungus Trichoderma citrinoviride. The structures of these compounds were elucidated using spectroscopic methods, including 1D and 2D nuclear magnetic resonance and high-resolution mass spectrometric analyses. Among these compounds, 4 and 5 showed moderate cytotoxic effects on the A-375 cell line, with IC50 values of 85.7 and 32.6 μM, respectively.

■ Solvent-Free Synthesis of New Chiral 3-Phenylamino-3,5-dihydro-4H-imidazol-4-one Derivatives from α-Amino Acid Phenylhydrazides

Yakdhane Kacem and Béchir Ben Hassine*

*Department of Chemistry, Faculty of Sciences, Laboratoire de Synthèse Organique Asymétrique et Catalyse Homogène, Avenue of the Environment, 5019 Monastir, Tunisia

Abstract

Enantiopure 2,5-disubstituted 3-phenylamino-3,5-dihydro-4H-imidazol-4-one derivatives were obtained in good to excellent yields by condensation of chiral α-amino acid phenylhydrazides and triethyl orthoesters in the presence of dry acetic acid as catalyst. All reactions are performed under solvent-free and mild conditions.

■ Synthesis of 6,7-Dihydrodibenzo[b,j]phenanthroline Derivatives by Pfitzinger Condensation of Isatin and Cyclic Diketones

Lizhen Fang,* Jinshuo Ma, Chenjuan Lu, Huanhuan Li, and Xiaoli Yang

*College of Pharmacy, Xinxiang Medical University, East of JinSui Road, XinXiang City, Henan Province, 453003, China

Abstract

All Two kinds of 6,7-dihydrodibenzo[b,j]phenanthroline derivatives were synthesized by Pfitzinger condensation of isatins with 1,3-cyclohexandione and1,4-cyclohexandione respectively. Structures of the derivatives were confirmed by NMR and other spectra data.