HETEROCYCLES

■ Contributions of Professor Gilbert Stork in Heterocyclic Chemistry

Jiro Tsuji

*Faculty of Engineering, Tokyo Institute of Technology, 2-12-1,Oh-Okayama, Meguro-ku, Tokyo 152-8552, Japan

■ An Approach to Indoloquionolizidine Alkaloids via Folate Models

Axel R. Stoit and Upendra K. Pandit

*Organic Chemistry Department, University of Amsterdam, Nieuwe Achtergracht 129, 1018 WS Amsterdam, The Netherlands

Abstract

Carbon fragment transfer via a 5,10-methylenetetrahydrofolate model has been utilized in the crucial step in the synthesis of heterocyclic systems related to indoloquinolizidine alkaloids.

■ Propellanes. Part LXXXIII. Solid State Conformations of Several Substituted Triaza[3.3.3]propellanes and of an Oxadiaza[3.3.3]propellane

Moshe Kapon, Menachem Kaftory, Philip Knowles, Olga Weinberg, and David Ginsburg

*Department of Chemistry, Israel Institute of Technology, Haifa 32000, Israel

Abstract

All of the title compounds have their five-membered rings in envelope conformations with the flaps all tilted in the same direction.

■ Reaction of Pyridine 1-Oxide with Methyl Propiolate: A Pyrido-oxepine and Other Novel Products

Rudolph A. Abramovitch, Dharma Kishore, Marek Konieczny, and Zbigniew Dauter

*Department of Chemistry, Clemson University, Clemson, SC 29631, U.S.A.

Abstract

The title reaction is much more complex than those of pyridine 1- oxides with other activated acetylenes. Eight products have been isolated and five characterized: 4-8. The most interesting is a pyrido-oxepin 8 whose structure has been firmly established by single crystal X-ray analysis The main products thus result from reaction of 3 moles of methyl propiolate with one mole of pyridine 1-oxide. The 1:1 (6) and 1:2 (7) adducts are very minor products.

■ Further Studies on Stereoselective Synthesis of Vicinal Diamines from 3,6-Dihydrothiazine-1-imines

Hideaki Natsugari, Edward Turos, Steven M. Weinreb, and Raymond J. Cvetovich

*Department of Chemistry, The Pennsylvania State University, York Campus, P1031 Edgecomb Avenue, York, Pennsylvania 17403, U.S.A.

Abstract

3,6-Dihydrothiazine-1-imines, prepared from a sulfur diimide and a 1-substituted 1,3-diene, can be transformed stereoselectively to either threo or erythro acyclic unsaturated vicinal diamine derivatives.

■ Degradations of 1-Methyl-3-benzenesulfonyloxyazine by Nucleophilic Reagents

James M. Hamby and Ludwig Bauer

*Department of Medicinal Chemistry, College of Pharmacy, University of Illinois at Chicago, P.O.Box 6998, Chicago, IL 60680, U.S.A.

Abstract

Degradation of 1-methyl-3-benzenesulfonyloxyalloxazine by nucleophilic reagents produced derivatives of 2-hydrazino-3-quinoxalinecarboxylic acid and anhydro-1-hydroxy-3-methyl-s-triazolo-[4,3-a]quinoxalinium hydroxide.

■ The Design and Synthesis of a Nonpeptide Mimic of Erabutoxin

Michael Kahn, Batbara Chen, and Paul Zieske

*Department of Chemistry, University of Illinois at Chicago, 845 West Taylor St., Chicago, IL 60607-7061, U.S.A.

Abstract

The synthesis of indolizidinone 1, a designed mimic of the proposed bioactive region of erabutoxin, a lethal venom protein, is detailed.

■ The Chemistry of Cyclic Vinyl Ethers 4: Cyclization of Unsaturated Cyclic Vinyl Ether Epoxides

Robert K. Boeckman, Jr., Jayaram R. Tagat, and Brian H. Johnston

*Department of Chemistry, University of Rochester, Rochester, NY 14627, U.S.A.

Abstract

The synthesis of [3Z,5S,6R] 2-[5,6-epoxy-undec-3-en-1-y1]-5,6-dihydro-4H- pyran (2) and [3Z,5S,6R] 2-[5,6-epoxy-undec-3-en-1-yl]-3,4-dihydrofuran (3) is outlined. Cyclization reactions of 2 and 3 catalyzed by various Lewis acids which proceed to afford spirocyclic ketals rather than the desired carbocycles are described.

■ Enantioselective Synthesis of 16-Membered α,β,γ,δ-Unsaturated Diolide: A Model System in Elaiophylin

Takeshi Wakamatsu, Satoshi Yamada, Hideo Nakamura, and Yoshio Ban

*Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan

Abstract

The synthesis of the entitled diolide (17) has been achieved starting from levoglucosan(l,6-anhydro-β-D-glucopyranose) (2) via the macrocyclization of the hydroxy acid (16) by reaction of mixed phosphoric anhydride procedure.

■ Synthetic Studies on Oxygenated Aspidoserma Alkaloids: Facile Syntheses of 1-Acetylaspidoalbidine and Deoxyaspidodispermine

Kiyoshi Yoshida, Yasuji Sakuma, and Yoshio Ban

*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan

Abstract

The electrophilic displacements of the reactive anion of tetracyclic lactam 3 were investigated. Facile syntheses of 1- acetylaspidoalbidine (5) and deoxyaspidodispermine (6) were achieved by the partial reduction of a lactam carbonyl, followed by the stereoselective transannular cyclization.

■ An Aromatic Version of Claisen Rearangement of Lactonic Silyl Enolates — A New Access to Potential Intermediates for Eudesmane Type of Sesquiterpenes

Hideo Nemoto, Eiki Shitara, Keiichiro Fukumoto, and Tetsuji Kametani

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

A new stereoselective synthesis of suitably substituted furanodecalins (9) ~ (12) via the Claisen rearrangement of furfuryl lactonic silyl enolate (6) derived from the furfuryl lactone (4) is described.

■ Intramolecural Photocycloaddition on Dioxolenones: An Efficient Method for the Synthesis of Medium-sized Rings

Jeffre D. Winkler, John P. Hey, Francis J. Hannon, and Paul G. Williard

*Searle Chemical Laboratories, Department of Chemistry, University of Chicago, 5735 South Ellis Avenue, Chicago, IL 60637, U.S.A.

Abstract

The intramolecular photocycloaddition of dioxolenones to simple olefins leads to the formation of six-, seven-, and eight-membered rings in good yields. Asymmetric induction in the formation of cyclooctanes is described.

■ Stereospecificity in Diels-Alder and 1,3-Dipolar Cycloadditions Does Not Prove the Concerted Mechanism

Raymond A. Firestone

*Medical Chemistry, Immunology and Inflammation Dept., Merck Sharp and Dohme, Research Laboratories, P.O.Box 2000, Rahway, NJ 07065, U.S.A.

Abstract

The exceptionally high stereospecificites in some recent cycloaddition cases do not rule out diradical intermediates, because (1) rotation barriers for free radicals >0, (2) those for diradicals may exceed those for free radicals, and (3) strain-free cyclizations t o 5- and 6-membered rings generally enjoy large rate advantages over their inrermolecular counterparts.

■ Photosensitized Oxyganetion of 2-Pyridones

Eisuke Sato, Yoshiya Ikeda, and Yuichi Kanaoka

*Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan

Abstract

Irradiation of oxygenated solutions of 3- and 6-substituted 2-pyridones with Methylene Blue as sensitizer afforded the oxygenation products probably by way of endoperoxide intermediates (4).

■ The Total Synthesis of (±)-Sikkimotoxin via the Benzo-Peterson Reaction

Seiichi Takano, Nobuaki Sato, Shizuo Otaki, and Kunio Ogasawara

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

The total synthesis of a lignan lactone sikkimotoxin (1) in racemic forms has been completed by employing the Benzo-Peterson reaction as key step.

■ Total Synthesis of (±)-Norsecurinine

Clayton H. Heathcock and Thomas W. von Geldern

*Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, U.S.A.

Abstract

The structures of the enantiomeric norsecurinines (2 and 3) have been confirmed by a total synthesis of (±) -2, starting with L-proline.

■ Reactions of Diphenylcyclopropenone with Hydrazine Derivatives: Formation of Pyrazolone Derivatives via 3-Aminocinnamohydrazides

Takashi Toda, Masaaki Yoshida, Tetsuo Katayama, and Masahiro Minabe

*Department of Applied Chemistry, Faculty of Engineering, Utsunomiya University, 7-1-2 Yoto, Utsunomiya 321-8585, Japan

Abstract

Reactions of diphenylcyclopropenone (1) with hydrazine or phenylhydrazine gave ring opening products (4,5- diphenylpyrazolones, 3) via 3-aminocinnamohydrazide derivatives (4). However, hydrazones (2) were obtained, in general, with 1 and hydrazine derivatives which possess electron accepting substituents under acidic conditions. Mechanism of the above reactions is discussed.

■ Synthesis and Electrochemical Behavior of 1,4-Dithiin Ring Condensed Systems

Toyonari Sugimoto, Iwao Sugimoto, Akihiko Kawashima, Yukishi Yamamoto, Yohji Misaki, and Zen-ichi Yoshida

*Faculty of Engineering, Kyoto University, Yoshida, Sakyou-ku, Kyoto 606-8501, Japan

Abstract

Alkylthio-substituted derivatives of 1,4-dithiin (1a), 1,4,5,8-tetrathianaphthalene (2a), 1,4,5,6,9,10-hexathiaanthracene (3a) and 1,4,5,6,7,10,11,12-octathianaphthacene (4a) are synthesized by Diels-Alder reaction of cis-1,2-dialkylthioethylenes or 2a with dimethyl tetrathiooxalate (6a) and the successive dehydrogenation with 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ). The electrochemical behavior of the new compounds (1b, 2b, 3b and 4b) and 2a is investigated by cyclic voltammetry. The skeletal rearrangement of 2a to tetrathiafulvalene (TTF) via the dication state, is found to occur by electrochemical or chemical means.

■ Circular Dichroic Spectra and Ionization Processes of Some Tropolonic Alkaloids

Daniela Walterova, Petr Malon, Frantisek Grambal, and Vilím Simánek

*Institute of Medical Chemistry, Palacky University, 3, Hnevotínská, 775 15 Olomouc, Czech Republic

Abstract

Some tropolonic alkaloids have been investigated by circular dichroic (CD) spectroscopy in dependence on pH. Their pK_a values in water-ethanol mixture (1:1) are given. Molar circular dichroism values ( δ ε ) are reported for all the measured alkaloids. The pH-depending changes in CD spectra are observed in demethylcolchicines and colchiceines. In the former they are associated with the ionization of phenolic groups in aromatic ring A, and in t h e latter with conformational changes of tropolonic rine C due to ionization of hydroxyl group at C-10.

■ A New, Efficient Synthesis of the Left Half of Narasin

Joseph A. Tino, Michael D. Lewis, and Yoshito Kishi

*Department of Chemistry, Harvard University, 12 Oxford Street, Cambridge, Massachysetts 02138, U.S.A.

Abstract

The coupling of the acetates 15a,b or 17a,b with the enol silyl ether 19 in the presence of ZnC1₂ was shown to yield exclusively the desired C.7 axial products. The stereoselectivity at the C.8 position was about 3.5:1 favoring the natural configuration.

■ A Chiral, Non-racemic C₁-C₇ Erythronolide Synthon Using the 3-Methyl-γ-butyrolactone Strategy

Frederick E. Ziegler and Alyssa Kneisley

*Sterling Chemistry Laboratory, Yale University, 225 Prospect St., New Haven, CT 06511, U.S.A.

Abstract

A chiral, non-racemic C₁-C₇ unit for the synthesis of the erythronolides has been prepared. R-3-Methyl-γ-butyrolactone serves as the template for the synthesis. The stereochemistry at C₃ of the synthon 13 was established by stereoselective , kinetic protonation of the enolates of lactones 9 and 10.

■ Regioselective Effects of the Allylic Heteroatoms in 1,3-Dipolar Cycloaddition of Nitrones to Several Allyl Derivativea

Yoshinobu Inouye, Satomi Niwayama, Tomonori Okada, and Hiroshi Kakisawa

*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki, 305-8571, Japan

Abstract

Further evidences that the allylic oxygen atom affects the regioselectivity in 1,3-dipolar cycloaddition of nitrones highly toward to produce 4-alkoxymethylisoxazolidines were presented. The selectivity was unaffected by the geometry of dipolarophiles.

■ An Asymmetric Total Synthesis of Unnatural (+)-Anisomycin

A. I. Meyers and Brian Dupre

*Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, U.S.A.

Abstract

Utilizing the valine-based chiral formamidine of 2,5-dihydropyrrole, enantioselective alkylation with p-methoxybenzyl chloride gave, after several subsequent synthetic manipulations, the unnatural enantiomer, (±)-anisomycin, in 22% overall yield and 88-90% ee.

■ Preparation and Cycloaddition of Functionalized 4,6-Dialikylpyrone-5-carboxylates. Synthesis of Bicyclic Lactones and Substituted Benzoates

Michael E. Jung and Jeffrey A. Hagenah

*Department of Chemistry and Biochemistry, University of California, 405 Hilgard Avenue, Los Angels, CA 90024, U.S.A.

Abstract

Several alkyl pyrone-5-carboxylates (coumalates) with alkyl and functionalized alkyl substituents at C4 and C6 have been prepared by a general route; their cycloadditions with electron-rich olefins have been carried out to provide aromatic and non-aromatic products, of potential value for natural products synthesis.

■ Efficient Synthesis of a New Penem Antibiotic, Sodium (5R,6S)-2-(2-Fluoroethylthio)-6-[(1R)-1-hydroxyethyl]penem-3-carboxylate

Isao Kawamoto, Rokuro Endo, Kosato Suzuki, and Tadashi Hata

*Chemical Research Laboratories and Analytical & Metabolic Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan

Abstract

Two useful routes to sodium (5R,6S)-2-(2-fluoroethylthio)- 6-[(1R)-1-hydroxyethyl]penem-3-carboxylate (1) via trithio-carbonate (3) are reported. An intramolecular Wittig reaction of 6 and an oxalimide cyclization of 9 with phosphite are employed as key steps.

■ The Reaction of Aliphtic Diazo Compounds with Highly Electrophilic Ethylene Derivatives

Ulrich Eichenauer, Rolf Huisgen, Abhijit Mitra, and Joaquin Rodriguez Moran

*Institut für Organische Chemie, Universität München, Karlstrasse 23, D-80333 München, Germany

Abstract

The cycloadditions of diazoacetic ester and diazomethane to tetracyanoethylene and ethylenetetracarboxylic ester, as well as reactions of the pyrazolines formed were investigated. In contrast to an earlier report, diazoacetic ester adds to the CC double bond of tetracyanoethylene.

■ Selective Chemical Transformations of the Trichothecene, 4β-Acetoxyscirpene-3α,15-diol

Ernest W. Colvin and Stuart Cameron

*Departmentof Chemistry, University of Glasgow, Joseph Black Building, Glasgow G12 8QQ Scotland, U.K.

Abstract

The deoxygenated trichothecene derivative (11), suitably functionalised for further selective transformation, has been synthesised efficiently from a naturally occurring trichothecene.

■ Macroring Contraction Methodology. 2. Total Synthesis of Haagenolide by [2,3]-Witting Rearrangement of 13-Membered Diallylic Ether

Takashi Takahashi, Hisao Nemoto, Yutaka Kanda, and Jiro Tsuji

*Department of Applied Chemistry, Graduate School of Science and Technology, Tokyo Instituteof Technology, Meguro-ku, Tokyo 152-8552, Japan

Abstract

A new route to construct the carbon skeleton of Haagenolide is described wherein the 13-membered diallylic ether 17, prepared by the cyanohydrin methodology, undergoes [2,3]-Wittig rearrangement to give the ten-membered carbocycles.

■ Synthetic Studies of the Nargenicins. 2. Synthesis of the "Northern Half" of Nargenicin A₁

James Kallmerten and Daniel J. Plata

*Department of Chemistry, Syracuse University, Syracuse, New York 13244-1200, U.S.A.

Abstract

The synthesis of intermediate 4, corresponding to the C₁-C₁₄ fragment of the nargenicin macrolides, is described.

■ A Novel synthesis of (±)-Noraporphine Alkaloids, (±)-Wilsonirine and (±)-Nordomesticine

Osamu Hoshino, Hiromichi Ogasawara, Masaji Suzuki, and Bunsuke Umezawa

*Faculty of Pharmaceutical Sciences,. Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan

Abstract

(±)-Wilsonirine (1a) and (±)-nordomesticine (1b) were synthesized in moderate yields on acid treatment, followed by alkaline hydrolysis of o-quinol acetates (o-QAs) (3) readily obtained by lead tetraacetate oxidation of (±)-N-trifluoroacetyltetrahydroisoquinolin-7-ols (2).