HETEROCYCLES

■ Contents

■ Transition Metal-Catalyzed Intramolecular Cyclization of Propargyl Alcohols and Their Derivatives for the Synthesis of Highly Substituted Five-Membered Oxygen Heterocycles

Masahiro Egi* and Shuji Akai*

*Synthetic Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan

Abstract

The transition metal-catalyzed intramolecular cyclization of propargyl alcohols and their derivatives has been widely utilized in the synthesis of five-membered oxygen heterocycles such as furans, hydrofurans, and furanones. Prerequisites for the efficient transformations into highly substituted target compounds include the regioselectivity of the cyclization step and the chemoselectivity of the transition metal-mediated activation of substrates. This review documents recent progress on the title reactions by categorizing the initial activation modes of substrates.

■ Divergent Synthesis of 2,6-Disubstituted Piperidine Alkaloid, (+)-Spectaline by Palladium-Catalyzed Cyclization

Masatomo Katsuyama, Masahiro Furuta, Kazuya Kobayashi, Kenta Teruya, Hidefumi Makabe, Kenichi Akaji, and Yasunao Hattori*

*Department of Medicinal Chemistry, Pharmacetuical Chemistry, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan

Abstract

Convergent synthesis of 2,6-disubstituted piperidine alkaloid, (+)-spectaline is described. Using substrate-controlled diastereo-selective Pd(II)-catalyzed cyclization, both cis-2,6- and trans-2,6-disubstituted piperidine backbones were constructed from adequately protected precursors with high selectivity. Synthesis of (+)-spectaline containing cis-2,6-disubstituents was accomplished by 10 step reactions with a 31% total yield.

■ Synthesis and Synthesis-Based Structural Elucidation of (‒)-Macrosphelides J and K

Hongchan An, Seung-Hee Kim, Heegyu Kim, Kyeojin Kim, Jaehoon Sim, Jaebong Jang, Seung-Mann Paek, Young-Ger Suh, and Hwayoung Yun*

*College of Pharmacy, Pusan National University, 63 Beon-gil 2, Busandaehag-ro, Geumjeong-gu, Busan 609-735, Korea

Abstract

The structures of (‒)-macrosphelides J and K have been elucidated via asymmetric total syntheses. Key points of the structure elucidation include an initial prediction of the stereochemistries of (‒)-macrosphelides J and K based on the structural relationship of the macrosphelides and molecular modeling of macrosphelide B. Our synthetic approach features an isoxazoline-based route involving a diastereoselective olefin-nitrile oxide cycloaddition, an intricate reductive N-O bond cleavage of an isoxazoline and O-alkylation of the labile β-hydroxy ketone intermediate.

■ Synthesis, X-Ray Structure and Metal Extracton Abilities of New Diethyl Phosphate Modified Thiacalix[4]arene

Kunda Uma Maheswara Rao, Takashi Kimuro, Manabu Yamada, Yoshihiko Kondo, and Fumio Hamada*

*Department of Applied Chemistry, Akita University, Tegata-gakuenncho 1-1, Akita 010-0852, Japan

Abstract

New lower rim modified phosphorylated thiacalix[4]arene (TC4A) derivatives such as TC4A-phosphate (2a) and de-t-Bu-TC4A-phosphate (2b) were synthesized. IR, 1H & 31P-NMR and mass spectral and elemental analysis characterized the structures of the synthesized compounds. Single crystal X-ray diffraction measurement reveals that, both the compounds (2a & 2b) stabilized in pinched cone conformation. We also investigated the metal extraction ability of the newly synthesized compounds through solvent extraction technique and these compounds selectively extracted Pd (II) ions from automotive catalyst residue solution containing nine metals.

■ Palladium-Catalyzed Suzuki Coupling towards 2-Amino-1,8-naphthyridines

Hangming Ge and Qiancai Liu*

*School of Chemistry and Molecular Engineering,, East China Normal University, Shanghai 200241, China

Abstract

Several 2-amino-6-aryl-1,8-naphthyridines were reported. The cyclocondensation of 2,6-diaminopyridine, 2-bromomalonaldehyde in phosphoric acid resulted in the formation of 2-amino-6-bromo-1,8-naphthyridine, which was converted into 2-amino-6-aryl-1,8-naphthyridines by palladium-catalyzed Suzuki reaction with arylboronic acid. It is shown that the Suzuki coupling with palladium catalyst (Pd-132) could be completed efficiently with lower catalyst loading and good to excellent yields. The title compounds were characterized by NMR spectra and mass spectra.

■ Four New Penicitrinols and Two New Penicillenols from the Marine-Derived Fungus Penicillium citrinum

Li Chen,* Tong Zhou, Yang-Yang Zhao, Mei-Wei Gong, Qi-Wen Xia, Min-Gang Ying, Qiu-Hong Zheng, Qin-Ying Liu, and Qi-Qing Zhang*

*Institute of Biomedical and Pharmaceutical Technology , Fuzhou University, Fuzhou, 350002, P. R. China

Abstract

Six new compounds, penicitrinols L–O (1–4), penicillenols D1 (9) and D2 (10), together with six known compounds were isolated from the marine- -derived fungus Penicillium citrinum. Their structures were elucidated on the basis of comprehensive spectral analysis and chemical methods. All the new compounds were evaluated for their cytotoxic effects on the A-549, HL-60 and SW-620 cell lines by the MTT method. Penicitrinols L (1) and M (2) showed weak cytotoxicities against SW-620 cell line, while penicillenols D1 (9) and D2 (10) showed weak cytotoxicities against A-549 and HL-60 cell lines, respectively.

■ Reaction of Lawesson’s Reagent with γ-Phosphonyloximes: Synthesis of Novel 1,2,5-Oxazaphospholine Derivatives

Aymen Wahbi and Soufiane Touil*

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

Abstract

The reaction of γ-phosphonyloximes with Lawesson’s reagent leads to a variety of new 1,2,5-oxazaphospholine derivatives. The reaction shows complete regioselectivity and gives a mixture of two diastereoisomers. The steric factors influencing the regioselectivity of the reaction are discussed and a mechanism accounting for the formation of the new compounds is proposed.

■ Organocatalytic Regioselective Three-Component, One-Pot Allylic Substitution of Morita-Baylis-Hillman Carbonates

Lin Jiang,* Jiang-Feng Zhou, Fei Li, Yong-Gen Li, Hong-Li Li, Yong-Ming Chuan, and Ming-Long Yuan*

*Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Engineering Research Center of Biopolymer Functional Materials, Yunnan Minzu University, 134 Yi Er Yi Avenue, Kunming, Yunnan, 650031, China

Abstract

A Lewis base mediated three-component, one-pot allylic substitution reaction of Morita-Baylis-Hillman (MBH) carbonates with water and 1-phenyl-5-methylsulfonyltetrazole (PTSO2Me) has been developed. In the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO), a series of 1-phenyl-5-functionalized tetrazoles are prepared in moderate to excellent yield (40-97%). The key reaction mechanism is rationalized by the ipso-substitution of PTSO2Me with hydroxide which derives from deprotonation of water.

■ New Anti-Oxidative Compounds from Rhinacanthus Nasutus

Ryuichiro Suzuki, Hiroshi Sakagami, and Yoshiaki Shirataki*

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

Abstract

Two new antioxidative compounds were isolated from methanolic extract of root of the Rhinacanthus nasutus. These chemical structures were elucidated by analysis of 1D and 2D NMR spectra including MS. Antioxidant activities of these isolates were determined by DPPH radical scavenging activity test. As the results, antioxidant activities of these isolates were comparative to Trolox used as a positive control. These isolates showed little or no detectable cytotoxicity against both human cancerous and normal cells.

■ Diasterospecific Etherification and Diasteroselective Monobromination of (R)-(—)-1-(2-Hydroxy-1-phenylethyl)-3,4-dihydropyridin-2(1H)-one

Anna Vargas, María L. Orea,* Joel L. Terán, David M. Aparicio, Jorge R. Juárez, Raúl G. Enríquez, and Dino Gnecco

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

Abstract

A one pot diasterospecific etherification and diasteroselective monobromination with bromine or N-bromosuccinimide (NBS) of the endocyclic enamide (R)-(—)-1-(2-hydroxy-1-phenylethyl)-3,4-dihydropyridin-2(1H)-one 1 is described. The enantiopure 8-bromo-3-phenyltetrahydro-2H-oxazolo[3,2-a]pyridin-5(3H)-ones trans-2 and cis-2 were obtained in good yield, fully characterized and its relative stereochemistry was unambiguously assigned via single-crystal X-ray structure.