HETEROCYCLES

■ Contents

■ Unprecedented Stereocontrol of β-Lactam Formation Derived from N-Cinnamylidenearylamine

Bimal K. Banik,* Hector Aguilar, and Daniel Cordova

*Department of Chemistry, The University of Texas-Pan American, 1201 West Univeristy Drive, Edinburg, Texas 78541, U.S.A.

Abstract

Formation of β-lactams by the reaction of acid chloride, N-cinnamylidenearylamine and a tertiary amine seems to involve multiple pathways. Microwave-induced irradiation and high temperature lead to preferential formation (95-100 %) of trans β-lactams derived from conjugated imines.

■ Investigation of the Regioselectivity on the Reaction of 2-Indolylcyanocuprate with N-(Prop-2-en-1-ylidene)aminium Chloride Derivatives

Minoru Ishikura,* Hiroyuki Komatsu, Koji Yamada, Takumi Abe, and Reiko Yanada

*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

Abstract

Regioselectivity on the reaction of (1-methylindol-2-yl)cyanocuprate with N-(prop-2-en-1-ylidene)aminium chlorides was investigated.

■ Synthesis of New Tricyclic Spirobispidines via Ring Closing Metathesis Reaction

Christian Hametner,* Daniel Dangl, Kurt Mereiter, Martina Marchetti, and Johannes Fröhlich

*Vienna University of Technology, Institute of Applied Synthetic Chemistry, Getreidemarkt 9/163, 1060 Vienna, Austria

Abstract

New tricyclic spiro compounds based on 3,7-diazabicyclo[3.3.1]nonane (bispidine) were synthesized by ruthenium-catalyzed ring closing metathesis reactions. The constitution of the newly formed double bond depending on the chain length and various conditions of the RCM reaction was analyzed.

■ Synthesis of 18-Hydroxyvincamines and Epoxy-1,14-secovincamines; A New Proof for the Aspidospermane-Eburnane Rearrangement

András Nemes,* Csaba Szántay Jr., László Czibula, and István Greiner

*Technological Research Laboratory No.I, Chemical Works of Gedeon Richter Ltd., H-1475 Budapest 10. POB 27., Hungary

Abstract

Chemical transformations started from tabersonine were studied. A one-pot oxidative ring-transformation with permaleic acid in methanol yielded 17,18-dehydrovincamine. Hydroboration-oxidation of the latter compound led to alkaloid 17,18-dehydrovincamone. Hydroboration-oxidation of tabersonine resulted 14β-hydroxyvincadifformine and 15β-hydroxyvincadifformine. Allowing 14β- and 15β- hydroxyvincadifformines to react with permaleic acid/methanol provided 1,14-secovincamines, serving as new evidence for the mechanism of the aspidospermane-eburnane transformation. On the other hand 18β-hydroxyvincamine was obtained from 14β-hydroxyvincadifformine by reaction with 3-chloroperbenzoic acid and successive treatment with triphenylphosphine/aqueous acetic acid.

■ A Novel Method for N3-Functionalized Aminoimidazolines and Aminopyrimidines by Aza-Michael Additions of Aminoimidazolines and Aminopyrimidines to α,β-Unsaturated Carbonyl Compounds

Xi-Cun Wang,* Cheng-Wei Lv, Zheng-Jun Quan, Guo-Li Huang, and Wen-Long Yang

*Gansu Key Laboratory of Polymer Materials, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, Gansu 730070, China

Abstract

An efficient and convenient procedure is described for the preparation of N3-functionalized aminoimidazolines and aminopyrimidines through the aza-Michael additions of aminoimidazolines and aminopyrimidines with α, β-unsaturated carbonyl compounds catalyzed by KF/Al₂O_3. This method offers a novel and efficient protocol for the N3-functionalized aminoimidazolines and aminopyrimidines with good regioselectivity and high purity under mild conditions.

■ Novel Method for the Synthesis of 3-Monosubstituted Six-Membered Benzosultams

Fang Fang, Rui Wang, Zhao-Peng Liu,* and Ai-Guo Ji

*Department of Organic Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, P.R. China

Abstract

3-Monosubstituted six-membered benzosultams with a wide range of functional groups were prepared by simple and convenient two-step procedures. o-Lithiation of N-Boc-o-toluenesulfonamide followed by reaction with aldehydes gave carbinol sulfonamides, which were converted to 3-monosubstituted six-membered benzosultams via TMSCl/NaI/MeCN reagent mediated cyclization. The mechanism and the scope of this novel transformation are studied.

■ The Oxidation of Benzo[b]thiophene Derivatives with DDQ — Preparation of π-Extended Hemithioindigoid Compounds

Hiroyuki Endo, Kinji Nagahama, Hidetsugu Wakabayashi, Makoto Kanazumi, Tatsuhisa Kato, and Keiji Kobayashi*

*Department of Chemistry, Graduate School of Material Science, Josai University, Sakado, Saitama 350-0295, Japan

Abstract

Hemithioindigoid compounds, e. g., 2-(6H-cyclopenta[1,2-b:4,3-b’]- bis[1]benzothiophen-6-ylidene)benzo[b]thiophene-3(2H)-one (1), were synthesized in good yields by the oxidation of benzo[b]thiophene derivatives such as 9-(2-benzo[b]thienyl)fluorene with DDQ in the presence of acid and under atmospheric oxygen. Under nitrogen, on the other hand, the reaction of 3 with DDQ resulted in an oxidative dimerization, the product of which was revealed to be equilibrated with radical species.

■ Heterocyclic Ortho-Aminocarbonyl Compounds in the Friedländer Reaction Promoted by Chlorotrimethylsilane

Sergey V. Ryabukhin,* Andrey S. Plaskon, Vasiliy S. Naumchik, Dmitriy M. Volochnyuk, Sergey E. Pipko, and Andrey A. Tolmachev

*Enamine Ltd. 23 A. Matrosova St., 01103 Kyiv, Ukraine

Abstract

A possibility of introduction of heterocyclic ortho-aminoketones into promoted by TMSCl Friedländer reaction with a wide set of α-methylenecarbonyl compounds was studied. A convenient synthetical method to obtain heterofused pyridine systems was elaborated; its scope and limitations were established as well. A set of derivatives of thieno[2,3-b]pyridines, [1]benzofuro[3,2-b]pyridines, 5H-chromeno[2,3-b]pyridin-5-ones, pyrido[2,3-d]pyrimidin-2,4(1H,3H)-diones was obtained in high preparative yields.

■ Syntheses and Anticholinesterase Activities of Novel 3-Aminocarbonylmethylene-3-methyl-2,3-dihydrobenzofuran-5-yl Carbamates

Weiming Luo, Qian-sheng Yu, Harold W. Holloway, David Tweedie, Damon Parrish, Arnold Brossi, and Nigel H. Greig*

*Drug Design & Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, U.S.A.

Abstract

Novel carbamates 4 and 5 were synthesized from starting material 5-hydroxy-3-methyl-3H-benzofuran-2-one, 17. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of 4 and 5 were determined against fresh human enzyme, are in the realm of clinically valuable compounds and are discussed. In addition, the reductive properties of the 2-carbonyl group of 3H-benzofuran-2-one, possessing an unsaturated substituted group in its 3 position (9, 11 and 14), were studied.

■ Copper Triflate Catalyzed Regioselective Alkylation of Pyrrole: Conversion of 2-Alkylated Pyrroles to Novel Pyrrolizine Derivatives by Self-Cyclization

Canan Unaleroglu,* Sertan Aytac, and Baris Temelli

*Hacettepe University, Department of Chemistry, 06800 Ankara, Turkey

Abstract

Metal triflate catalyzed addition reaction of pyrrole to methyl 2-oxo-4-phenylbut-3-enoate and substituted derivatives generated the related novel alkylated pyrroles regioselectively at C(2) of pyrrole. Among the studied metal triflates, Cu(OTf)₂ was found to be more effective in the addition reaction. The synthesized methyl 2-oxo-4-phenyl-4-(1H-pyrrole-2-yl)butanoate esters underwent self-cyclization by heating and yielded the corresponding methyl 3-hydroxy-1-phenyl-2,3-dihydro-1H-pyrrolizine-3-carboxylate and substituted derivatives. This reaction procedure allowed easy access to pyrrolizine structure in mild reaction conditions.

■ Three New ent-Kauranoids from Isodon phyllostachys

Xian Li, Jianxin Pu, Shenghong Li, Shengxiong Huang, Zhiying Weng, Quanbin Han, and Handong Sun*

*State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, Yunnan, P.R. China

Abstract

Three new ent-kaurane diterpenoids, phyllostacins C-E (1-3), together with six known analogues, oridonin (4), ponicidin (5), effusanin A (6), rabdoternin E (7), rabdoternin F (8), and macrocalyxoformin E (9), were isolated from the aerial parts of Isodon phyllostachys. The structures of compounds (1-3) were determined on the basis of spectroscopic methods including extensive 1D and 2D NMR analysis. All compounds were evaluated for their inhibitory activity against K562, HL60 and HepG2 (hepatoma) cell lines.

■ Synthesis of Aza-Analog of N-Methylated Acycloformycin A

Mariusz Mojzych* and Andrzej Rykowski

*Department of Chemistry, University of Podlasie, 08-110 Siedlce, Poland

Abstract

Starting from 3-methyl-5-methylsulfanyl-1H-pyrazolo[4,3-e][1,2,4]- triazine (1) by reaction with methyl iodide, subsequent oxidation, ipso-substitution with hydrazine and reaction with yellow mercury (II) oxide 1,3-dimethyl-1H-pyrazolo[4,3-e][1,2,4]triazine (14) is prepared. Further radical bromination and treatment with ethylene glycol in the presence of potassium carbonate afforded 3-(2-hydroxy-ethoxymethyl)-1-methyl-1H-pyrazolo[4,3-e]- [1,2,4]triazine (16) as aza-analog of N-methylated acycloformycin A.

■ Nitration of Dimethyl 1-Substituted Indole-2,3-dicarboxylates: Synthesis of Nitro- and Aminoindole Derivatives

Yasuyoshi Miki,* Misako Umemoto, Hiroko Maruyama, Makoto Kuromatsu, and Hiromi Hamamoto

*Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1, Kowakae, Higashi-Osaka 577-8502, Japan

Abstract

The treatment of dimethyl indole-2,3-dicarboxylate with nitronium tetrafluoroborate in the presence of tin (IV) chloride produced dimethyl 5 nitroindole-2,3-dicarboxylate as the major product. In a similar manner, the dimethyl 1 benzyl- and 1-benzenesulfonylindole-2,3-dicarboxylates provided a mixture of the corresponding 4-nitro-, 5 nitro-, 6-nitro- and 7-nitroindole derivatives. However, dimethyl 5-bromoindole-2,3- dicarboxylate gave dimethyl 5-bromo-4-nitroindole-2,3-dicarboxylate as the sole product, which was converted to dimethyl 4-aminoindole-2,3-dicarboxylate.

■ Synthesis and Redox Ring Cleavage of cis-1,3,4,5-Tetrahydrobenzo[c]oxepines

Xinfang Duan, Xiali Xu, Zhanbin Zhang,* and Zhibing Zheng

*Department of Chemistry, Beijing Normal University, Beijing, 100875, China

Abstract

A series of cis-1,3,4,5-tetrahydrobenzo[c]oxepines was conveniently prepared via the oxa-Pictet-Spengler reaction catalyzed by boron trifluoride etherate in dioxane at room temperature. Experiments proved that the construction of these heterocyclic compounds via this methodology was highly acid (catalyst)- and reaction condition-dependent. An unexpected redox ring cleavage reaction occurred when unsuitable acids or reaction conditions were employed.

■ Prenylated Flavonoids from Tephrosia apollinea

Mohamed H. Abd El-Razek,* Abou El-Hamd H. Mohamed, and Ahmed A. Ahmed

*National Research Center, Natural Products Chemistry Department, El-Tahrir, St., Dokki, Cairo 12622, Egypt

Abstract

Re-investigation of the chloroform extract of the aerial part of Tephrosia apollinea afforded seven new 8-prenylated flavonoids namely tephroapollin A-G (1-7). The structures were established by spectroscopic methods, including HR-CI-MS, ¹H, ¹³C, DEPT, HMQC, HMBC and ROESY experiments. The relative configuration analysis of stereocenters for 5-7 was carried out on the basis of the reported J-based method. General toxicity of the isolated compounds was determined by brine shrimp lethality bioassay.

■ The First Synthesis of Protected 5-Hydroxymethyl-2-cyanomethylbenzimidazole

Isamu Katsuyama* and Masanori Kubo

*Hitec Co., Ltd., 1-8-30 Temmabashi, Kita-ku, Osaka-shi, Osaka 530-6025, Japan

Abstract

Protected 5-hydroxymethyl-2-cyanomethylbenzimidazole 4 has successfully been synthesized starting from 3,4-diaminobenzoic acid 1. The benzimidazole 4 is expected to be a useful intermediate for the synthesis of new functional molecules such as drugs, agrochemicals, dyes, perfumes, and cosmetics.