HETEROCYCLES

■ Contents

■ Photoinduced Electron Transfer-Initiated Cyclization Reactions and Asymmetric Transformations of (Z)-α-Dehydroamino Acid Derivatives

Tetsutaro Igarashi and Tadamitsu Sakurai*

*Department of Material and Life Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan

Abstract

We systematically investigated the cyclization reactions of N-acyl-α-dehydroamino acid derivatives, initiated by electron transfer (ET) from aliphatic amines to these derivatives in the excited state. On the basis of the percent conversion of the starting α-dehydroamino acid and the composition of the cyclization products, we demonstrated that the photoinduced ET reactions of N-acyl-α-dehydroarylalaninamides, 1,2,4-triazole-substituted α-dehydroarylalaninamides, and N-acyl-α-dehydroarylalanine alkyl esters efficiently proceeded to afford various 3,4-dihydroquinolinone; quinolinone; and 4,5-dihydrooxazole derivatives, respectively, with high selectivities. In addition, the introduction of chiral auxiliary groups into N-acyl-α-dehydroamino acid amide and ester derivatives and the presence of chiral aliphatic amines induced efficient diastereoselective and enantioselective photocyclization reactions of these amide and ester derivatives, respectively, to enable the construction of the chiral dihydroquinolinone and dihydrooxazole rings.

■ Synthesis and Characterization of Phenyl(1,3,6,8-tetraazatricyclo[4.3.1.13,8]undecan-4-yl)methanone and Its Derivatives

Cong Liu, Rongji Dai,* Guowei Yao, and Yulin Deng*

*School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street Beijing 100081, China

Abstract

A quick and highly efficient method for the synthesis of phenyl(1,3,6,8-tetraazatricyclo[4.3.1.13,8]undecan-4-yl)methanone and its derivatives from hexamine and 2-bromo-1-arylethanones has been established via a Stevens rearrangement. Structures of the products were characterized by NMR and X-ray crystallography.

■ Enantioselective Intramolecular Aza-Spiroannulation onto Benzofurans Using Chiral Rhodium Catalysis

Takuro Shibuta, Shigeki Sato, Masatoshi Shibuya, Naoki Kanoh, Tohru Taniguchi, Kenji Monde, and Yoshiharu Iwabuchi*

*Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aobayama, Sendai 980-8578, Japan

Abstract

The development of efficient and enantioselective intramolecular aza-spiroannulation onto benzofurans using chiral rhodium catalysis is described. The optimized reaction conditions [Rh2(S-TCPTAD)4 (3 mol %), PhIO (1.6 equiv), MeOH (10 equiv) in PhCF3, 0 °C] brought about oxidative aza-spiroannulation of 3-(carbamoylmethyl)benzofuran (3) resulting in (2R,3S)-2-methoxy-2H-spiro- [benzofuran-3,4'-oxazolidin]-2'-one (15a) in 69% yield with 86% ee, the absolute structure of which was determined by a combination of X-ray crystallography and vibrational circular dichroism (VCD) spectroscopy. The reaction is applicable to the asymmetric construction of various 2,3-dihydrobenzofuran derivatives bearing a nitrogen-containing tetrasubstituted carbon stereocenter at C3 (up to 92% ee).

■ Synthesis of Pyrazoles Based on Functionalized Allenoates

Ilshat M. Sakhautdinov,* Aynur M. Gumerov, Ilnur R. Batyrshin, Akhnaf A. Fatykhov, Kyrill Yu. Suponitsky, and Marat S. Yunusov

*Institute of Organic Chemistry, Bioorganic Chemistry, Ufa Research Centre, Russian Academy of Sciences, Prospect Oktyabrya, 71, 450054, Ufa, Russia

Abstract

Regiospecific synthesis of pyrazole-3-carboxylate derivatives by 1,3-dipolar cycloaddition of diazomethane with allenoates in presence of triethylamine is demonstrated. Reaction of allenoates with stearic acid moiety containing diazoketone is explored under ultrasonic conditions. Novel derivatives of pyrazole were achieved in excellent yields.

■ Bisindole Alkaloids Condensed with a Cyclopropane Ring, Part 1. 14,15-Cyclopropanovinblastine and -vincristine

Péter Keglevich, László Hazai, Zsófia Dubrovay, Miklós Dékány, Csaba Szántay, Jr., György Kalaus, and Csaba Szántay*

*Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1111 Budapest, Szt. Gellért tér 4, Hungary

Abstract

A new type of vinblastine and vincristine derivatives was synthesized. The carbon carbon double bond in position 14 and 15 of the vindoline ring was cyclopropanated. In the course of the synthetic work 14,15-cyclopropanovindoline was coupled with catharanthine, resulting in the cyclopropanated anhydrovinblastine as a key intermediate to 14,15-cyclopropano-vinblastine and -vincristine.

■ Enantioselective Total Synthesis of (–)-Scabronine D

Yu Kobayakawa and Masahisa Nakada*

*Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan

Abstract

The first enantioselective total synthesis of (–)-scabronine D comprising a unique bridged hemiacetal is described. The total synthesis is successfully accomplished using an enantiopure intermediate prepared in the total synthesis of (–)-scabronines G and A, and (–)-episcabronine A. Because the advanced intermediate was found to be sensitive to basic reaction conditions, the C14 keto and C11 hydroxy groups had to be co-protected as methyl acetal. In addition, both the C15 hydroxy and C17 carboxyl groups were too reactive to be chemically discriminated; hence, the carboxyl group once formed was protected as a tert-butyl ester for ensuring successful transformations.

■ Synthesis of the Precursors of Pumiliotoxin 251D and Awajanomycin and Related Studies

Shang-Shing P. Chou,* Kuo-Shiun Yang, and Tzu-Han Chiu

*Department of Chemistry, Fu Jen Catholic University, 510 Chung-Cheng Rd., Hsin-Chuang, New Taipei City 24205, Taiwan, R.O.C.

Abstract

The aza-Diels–Alder reaction of 3-phenylthio-3-sulfolenes with p-toluenesulfonyl isocyanate (PTSI) gave trans-5,6-dihydropyridinones, which upon treatment with NBS afforded the trans-allylic bromides. Hydrolysis of the bromides provided the allylic alcohols with retention of configuration. Further synthetic transformations led to the formal synthesis of pumiliotoxin 251D and awajanomycin. Some related syntheses are also reported.

■ Facile Synthesis of 2-Phenylquinoline-4-carboxamide Derivatives with Variant Structural Features

Rafiqul Islam, Md. Imran Hossain, Yoshinari Okamoto, Tomohisa Nagamatsu, Kensaku Anraku, and Tadashi Okawara*

*Medical Technology, Faculty of Health Science, Kumamoto Health Science University, 325 Izumimachi Kumamoto 881-5598, Japan

Abstract

The quinoline scaffold is an important class of heterocyclic compounds that possesses diverse chemotherapeutic activities. Thus, the 2-phenylquinoline-4-carboxamide derivatives containing a variety of moieties, such as 2-(2-furanyl)-1,3,4-oxadiazole, N-(2-methylphenyl)-4-(3-pyridinyl)-2-pyrimidinamine, 4,4'-bithiazole, purine, adamantine and resorcinol, have been designed and synthesized via Suzuki coupling, acid-base coupling and other typical reactions.

■ Dakin-West Reaction of N-Thioacylprolines Using Trifluoroacetic Anhydride: Novel Access to 5-Trifluoromethylthiazoles

Yuri Hagimoto, Ryosuke Saijo, and Masami Kawase*

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

Abstract

The reaction between N-thioacylprolines and trifluoroacetic anhydride in the presence of pyridine afforded a good yield of 5-trifluoromethylthiazoles. This reaction proceeded through mesoionic 1,3-thiazolium-5-olates, followed by cleavage of the pyrrolidine ring and the formation of thiazoles, introducing a trifluoromethyl group at position 5 in the thiazole ring.

■ Oxidation and Aromatization of the Enantiopure Piperidine Derived from (R)-(-)-2-Phenylglycinol to (1’R)-(-)-1-(2’-Hydroxy-1’-phenylethyl)-1H-pyridin-2-one

Alejandro Castro, Oscar Romero, Joel L. Terán, Dino Gnecco, Laura Orea, Angel Mendoza, and Jorge R. Juárez*

*Centro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Edif. 103G, 103H, 72570, Mexico

Abstract

An efficient oxidation of enantiopure piperidine 1 with bromine in acetic acid to generate the corresponding enantiopure (R)-3,3-dibromo-1-(2’-hydroxy-1’-phenylethyl)piperidin-2-one 2 is described. Then, aromatization of compound 2 to give enantiopure pyridin-2-one 3 in 71% overall yield is presented.

■ New Compounds from Tabebuia avellanedae

Li Zhang, Isao Hasegawa, Takanori Tatsuno, Tetsuro Kawabata, Tomihisa Ohta, and Takeshi Tadano*

*School of Pharmacy and Pharmaceutical Sciences, Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192, Japan

Abstract

Two new compounds, a compound firstly isolated from plants, a known iridoid and four known lignan derivatives were isolated from water extract of Tabebuia avellanedae. The chemical structures and relative configurations of the new compounds were determined by 1D, 2D NMR and MS spectroscopic analyses.

■ Synthesis of 10-Substituted Benzo[b][1,8]naphthyridin-5(10H)-ones Based on the Reaction of (2-Chloropyridin-3-yl)(2-halophenyl)methanones with Primary Amines

Kazuhiro Kobayashi,* Shohei Yuba, and Toshihide Komatsu

*Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

The reaction of (2-chloropyridin-3-yl)(2-halophenyl)methanones, derived from 2-chloropyridine and 2-halobenzaldehydes, with two equivalents of benzenamines or arylmethanamines followed by treatment of the resulting (2-aryl(or arylmethyl)aminopyridin-2-yl)(2-halophenyl)methanones with sodium hydride in DMF at 0 ˚C to room temperature have proven to provide an efficient method for the preparation of 10-aryl(or arylmethyl)benzo[b][1,8]naphthyridin-5(10H)-ones. This methodology is shown to be applicable for the preparation benzo[b][1,7]naphthyridin-5(10H)-one derivatives by using 3-chloropyridine as a starting material in place of 2-chloropyridine.

■ Serralongamine A, a New Lycopodium Alkaloid from Lycopodium serratum var. longipetiolatum

Wen-Ping Jiang, Kan'ichiro Ishiuchi, Jin-Bin Wu,* and Susumu Kitanaka*

*Organic and Material Synthesis Laboratory, Graduate Institute of Pharmaceutical Chemistry, China Medical University, No. 91 Hsueh-Shih Rd. Taichung 40402, Taiwan

Abstract

A new Lycopodium alkaloid, serralongamine A (1), has been isolated from the club moss Lycopodium serratum var. longipetiolatum, and the structure was elucidated on the basis of spectroscopic data.

■ Simple and Efficient Synthesis of Phosphorylated Thienopyridones from 2-Aminothiophene-3-carboxylates and β-Phosphonylketones

Khaoula Khalladi and Soufiane Touil*

*Department of Chemistry, Faculty of Sciences of Bizerta, 7021-Jarzouna, Tunisia

Abstract

Herein, we report an efficient and straightforward synthesis of the new 5-phosphonothieno[2,3-b]pyridin-4(5H)-ones, via the p-toluenesulfonic acid catalyzed reaction of ethyl 2-aminothiophene-3-carboxylates with β-phosphonylketones. To the best of our knowledge, this is the first synthesis of thienopyridone derivatives bearing a phosphonate or a phosphine oxide group.

■ Synthesis of a Phosphatidylinositol Dimannoside Using 2-(Azidomethyl)benzoate Mannosyl Donors

Shuichi Ohira, Yoshiki Yamaguchi, Takashi Takahashi, and Hiroshi Tanaka*

*Department of Applied Chemistry, Graduate School of Science and Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8552, Japan

Abstract

We report on the synthesis of an acyl phosphatidylinositol dimannoside using the 2-(azidomethyl)benzoate-protected mannosyl donors. An equatorial-orientated C6 hydroxyl group in inositol exhibited higher reactivity towards glycosylation than the axial-orientated C2 hydroxyl group. Sequential glycosylation of the C6 and C2 hydroxyls with two different thioglycosides allowed the synthesis of a 2,6-di-O-α-mannosyl inositol in one-pot. After incorporation of a fatty acid and an acyl phosphatidyl moiety, all protecting groups involving benzyl ethers, benzylidene acetal and the 2-(azidomethyl)benzoate were removed under hydrogenolysis to provide an acyl phosphatidylinositol dimannoside.