HETEROCYCLES

■ Profile and Scientific Contributions of Professor R. B. Woodward

Harry H. Wasserman*

*Department of Chemistry, Yale University, P.O. Box 6666, New Haven, Connecticut 06511, U.S.A.

■ Bibliography

R. B. Woodward*

*,

■ Robert Burns Woodward: Three Score Years and Then?

David Dolphin*

*Department of Chemistry, University of British Colombia, 2063 Main Mall, Vancouver B.C. V6T 1Z1, Canada

■ A Facile Synthesis of 3-Benzazepine and Dibenzazonine Derivatives

Hans Bieräugel, Hans-Paul Soetens, and Upendra K. Pandit*

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

Abstract

A two-step synthesis of methanodibenzazonine and azepine derivatives starting from readily obtainable isoquinolinium salts is described.

■ Oxidative Ring Cleavage of Coralyne Alkaloid

Yoshikazu Kondo,* Hideo Inoue, and Jiro Imai

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

Abstract

Oxygenation of coralyne alkaloid, a nonenzymic model of the oxygenase, has been investigated. A solution of dihydrocoralyne 1 or 13-hydroxycoralynium betaine 2 in the presence of sodium alkoxide was allowed to contact with air under illumination of visible light to give 6,7-dimethoxyisoquinolone-1 3 and the corresponding 3-methyl-3-alkoxy-5,6-dimethoxyphthalide 4 or 5. When the same autoxidation was carried out in the presence of borohydride anion, 3 and 3-methyl-5,6-dimethoxyphthalide 6 were obtained along with 13-hydroxycoralydine. Oxygenation of 2 in the presence of cuprous chloride led to 2’-acetylpapaveraldine 11. On the other hand, irradiation of 2 in chloroform in the presence of Rose Bengal gave a 1 : l mixture of 11 and 2’-carbomethoxypapaveraldine 12. The mechanisms were also discussed.

■ Synthesis of Isoxazolo[5,4-b]pyridines and Isoxazolo[5,4-d]pyrimidines from 5-Aminoisoxazoles

Hiroshi Yamanaka,* Takao Sakamoto, and Akira Shiozawa

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

Abstract

3-Phenyl-4-formyl-5-aminoisoxazole (III) was synthesized by the Vilsmeier reaction of 3-phenyl-5-aminoisoxazole (I) via a stable intermediate, 3-phenyl-4-formyl-5-dimethylaminomethyleneaminoisoxazole (III). Condensation of III with β-keto acids and amidine derivatives afforded isoxazolo[5,4-b]pyridines and isoxazolo[5,4-d]pyrimidines, respectively.

■ The Birch Reduction of Quercetin Methayl Ethers

James G. Sweeny, Terence Radford, and Guillermo A. Iacobucci*

*Corporate Research and Development, The Coca-Cola Company, P. O. Drawer 1734, Atlanta, GA 30301, U.S.A.

Abstract

The sodium-ammonia reduction of 3,3’,4’,5,7-pentamethylquercetin (I) afforded the dihydrochalcone (II) in 54% yield. In contrast, the reduction of 3’,4’,5,7-tetramethylquercetin (III) yielded the α-hydroxydihydrochalcone (IV) (64% yield) as major product. The reactions are believed to proceed through the intermediary formation of 2,3-trans-dihydroquercetins.

■ Flash Photolysis of α-Cyano-cis- and -trans-stilbene Oxide; Energy Profile of cis, trans Isomerization via Carbonyl Ylides

Rolf Huisgen,* Volker Morkowski, and Horst Hermann

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

Abstract

Flash photolysis of the title compounds in the matrix at -196 °C produces blue and red colors which disappear with half-reaction times of 5.0 and 0.25 sec. The colors are attributed to cis, trans isomeric carbonyl ylides which decay via thermal recyclization. An ensemble of kinetic data provides estimates of upper and lower bounds for the recyclization and rotational barriers of the carbonyl ylides at 129.6 °C.

■ Syntheses and Properties of meso-Methyl Porphyrins and Chlorins

Michael J. Bushell, Brian Evans, George W. Kenner, and Kevin M. Smith*

*Department of Organic Chemistry, The Robert Robinson Laboratories, University of Liverpool, P.O.Box 147, Liverpool L69 3BX, U.K.

Abstract

Good overall yields of meso-methylporphyrins (3) or chlorins (1,2), are obtained by reduction of the appropriate formyl derivative, followed by acetylation with acetic anhydride in pyridine of the resulting hydroxymethyl compound and reduction with Pd-C/H₂ or NaBH₄.

■ 2-Substituted-amino-5-phenyl-1,3,4-oxadiazoles

Keith L. Turner and Stephen Turner*

*Reckitt & Colman Pharmaceutical Division, Dansom Lane, Hull, HU8 7DS, U.K.

Abstract

The sodium salt of 2-acetamido-5-phenyl-1,3,4-oxadiazole can be alkylated using activated bromides. Alkylation by an unactivated halide takes place intramolecularly. The N-substituted compounds and derivatives thus prepared were essentially inactive in a screening system for CNS activity.

■ Synthesis of Oxazoles, Imidazoles and Pyrroles with the Use of Mono-substituted Tosylmethyl Isocyanides

Okko Possel and Albert M. van Leusen*

*Department of Organic Chemistry, University of Groningen, Zernikelaan, Groningen, The Netherlands

Abstract

Oxazoles, pyrroles and imidazoles are synthesized from mono-alkylated tosylmethyl isocyanides (TosCHRN=C) and aldehydes, Michael-acceptors or aldimines.

■ Cyclophanes XI. The Synthesis and Comformational Behavior of 3,6-Diketo[8](2,5)thiophenophane. (3,6-Diketo[8](2,5)thiophenophane)

Alice W. Lee, Philip M. Keehn,* Socorro M. Ramos, and Stuart M. Rosenfeld

*Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA 02454-9110, U.S.A.

Abstract

3,6-Diketo[8](2,5)thiophenophane (1c) was synthesized by hydrolysis of [2.2](2,5)furano(2,5)thiophenophane (3). The conformational behavior of the thiophene ring and the diketo-chain in 1c was then studied by variable temperature nuclear magnetic resonance techniques. With similar studies on the deuterated derivative 5, the energy barrier associated with ring and chain flipping was found to be 16.0 and 11.4 kcal/mol, respectively. This is the first case in which a thiophenoid nucleus within a cyclophane macrocycle is found to be mobile and the first instance in which the conformational motions and associated energetics of both the aromatic ring and aliphatic chain in a cyclophane have been established.

■ Photodimerization of Indole Derivatives

Tohru Hino,* Mikio Taniguchi, Tadamasa Date, and Yoichi Iidaka

*Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan

Abstract

1,3-Diacetylindole (I) gave cyclobutane-dimer (II) by irradiation in various solvents.

■ A New Synthesis of 2-Amino-2-thiazolines (2-Aminodihydro-1,3-thiazoles)

Paul D. Woodgate,* Ho H. Lee, Peter S. Rutledge, and Richard C. Cambie

*Department of Chemistry, University of Auckland, Private Bag 92019, Auckland, New Zealand

Abstract

2-Phenylamino-2-thiazolines are readily prepared under mild conditions by the reaction of aniline with vic-iodoisothiocyanates. Ammonia, and primary and secondary alkylamines each give clean reactions with trans-1-iodo-2-isothiocyanatocyclohexane but not with 2-iodo-1-phenyl-1-isothiocyanatoethane.

■ Altholactone, a Novel Tetrahydrofuro[3,2-b]pyran-5-one from a Polylthia Species (Annonaceae)

John W. Loder* and Roland H. Nearn

*Division of Applied Organic Chemistry, CISRO, P. O. Box 4331, Melbourne 3001, Australia

Abstract

Altholactone has tentatively been assigned the structure 3-hydroxy-2-phenyl-2,3,3a,7a-tetrahydro-5H-furo[3,2-b]pyran-5-one (I) on the basis of its chemical reactions and physical properties.

■ The Synthesis of (3S,5S)-5-Hydroxyhexahydropyridazine-3-carboxylic acid

Cedric H. Hassall* and Kuzhalmannam L. Ramachandran

*Roche Products Ltd, Welwyn Garden City, Herts, U.K.

Abstract

The compound named in the title, a naturally occurring amino acid, has been synthesised from the Diels-Alder adduct of penta-2,4-dienoic acid to phthalazinedione, through successive oxidation with mercuric acetate, hydrogenation with Rh-Al₂O₃ catalyst, acid hydrolysis, resolution with quinine, and hydrazinolysis.

■ Synthesis of 11-Azaprostaglandin Analogs

Gerard P. Rozing, Henk de Kohnig,* and Henderikus O. Huisman

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

Abstract

11-Deoxy-11-azaprostaglandin derivatives are obtained in eight steps, starting from methyl N-ethoxycarbonylglycinate and ethyl 4-tert-butoxycrotonate. The synthesis of an aza-analog of the “Corey-lactone” is described.

■ A Route for Total Synthesis of Chelidonine Group of Alkaloids

Ichiya Ninomiya,* Okiko Yamamoto, and Takeaki Naito

*Kobe Women’s College of Pharmacy, Motoyamakita, Higashinad, Kobe, Hyogo 658, Japan

Abstract

A potential synthetic route (V → III) for total synthesis of chelidonine (I) and homochelidonine (II)¹ was developed using the model compounds (V-X).

■ Total Synthesis of the Alkloids Homochelidonine

Ichiya Ninomiya,* Okiko Yamamoto, and Takeaki Naito

*Kobe Women’s College of Pharmacy, Motoyamakita, Higashinad, Kobe, Hyogo 658, Japan

Abstract

Homochelidonine (I) was synthesised for the first time by the route including enamide photocyclisation.

■ Synthesis of (±)-Emetine from Protoberberine Precursor via the α-Diketone Monothioletal Intermediate

Seiichi Takano,* Makoto Sasaki, Hideyuki Kanno, Kozo Shishido, and Kunio Ogasawara

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

Abstract

A synthesis of (±)-emetine (1) is accomplished using 2,3,11-trimethoxytetrahydroprotoberberine (3) as a starting material via the α-diketone monothioketal intermediate (8). Compound (3) was converted to the α-diketone monothioketal derivative (8) through a 4 step-sequence. The intermediate (8) upon treatment with potassium hydroxide, followed by desulfurization yielded the protoemetine derivative (11). (±)-Emetine (1) was obtained from 11 by a series of classical methods.

■ A New Synthetic Route to Indoliquinolizidine Alkaloids

Tozo Fujii,* Shuigeyuki Yoshifuji, and Harue Ito

*Faculty of Pharmaceutical Scicences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan

Abstract

Syntheses of 1-[2-(3-indolyl)ethyl]-2-piperidone (Va) dl-trans-1-[2-(3-indolyl)ethyl]-5-ethyl-2-oxo-4-piperidineacetate (Vb) from the lactams 1a,b have been accomplished in acceptable overall yields through the lactim ethers IIa,b, the lactam ketones IIIa,b, and the lactam alcohols IVa,b, concluding formally the total syntheses of 1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine (VIa), dl-dihydrocorynantheine (VId), and related alkaloids (VIc,e).

■ A New Approach to the Skeleton of Rauwolfia Alkaloids

Csaba Szántay,* Gábor Blaskó, Katalin Honty, Lajos Szabó, and László Töke

*Institute for Organic Chemistry, Technical University Budapest, H-1521 Budapest, P.O. Box 91Gellért tér 4, Hungary

Abstract

The reaction of enamine derivative 2 with ethyl α-acetoxyacrylate gave the indolo[2,3-a]quinolizidine derivative 3a. From 3a the characteristic structure of the Rauwolfia alkaloids has been built up by stereoselective reactions.

■ Rupestralic Acid, a New Diterpene Lactone

Giuseppe Savona, Franco Piozzi,* and Marialuisa Marino

*Dipartimento di Chimica Organica, Università digli Studi di Palermo, Via Archirafi 20 90123 Palermo, Italy

Abstract

Rupestralic acid, extracted from Ballota rupestris (Labiatae) is assigned structure [III]-[IV]. The reaction with diazomethane yields an unstable epoxy ester [V] which changes either into the methyl ketone [VI] or into the lactone [VII]. An interesting fragmentation is evidenced in the mass spectra of such compounds.

■ Synthesis of Functionally Substituted 1-Azaadamantanes Anomalous 1,3-Diol Fragmentaion

W. Nico Speckamp* and Hans van Oosterhout

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

Abstract

The synthesis of a number of 2- and 3-substituted 1-azaadamantanes, in which the substituent carries a functional group, is reported. Anomalous fragmentation of a 1,3-diol is described and discussed in terms of conformation.

■ Synthesis of 1,5-Dienes and 6-Azabicyclo[3.2.1]octanes via ω-Carbinollactams

Anthonia R. C. Oostveen, Jan J. J. de Boer, and W. Nico Speckamp*

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

Abstract

3,3-Disubstituted succinimides are reduced regioselectively at the 2 and 5 positions. The resulting ω-carbinol-lactams are used for synthesis of 6-phenyl-1,5-dienes and 6-azabicyclo[3.2.l]octanes, respectively.

■ Synthesis of 1-(5’-Deoxy-β-D-erythropent-4’-enofuranosyl)isocytosine and 2-N,5‘-Anhydroisocytidine

Vinko Skaric,* Jasenka Matulic-Adamic, and Djurdja Skaric

*Laboratory fo Stereochemistry and Natural Products, "Ruder Boskovic" Institute, Bijenicka 54, P.O. Box 1016 41001 Zagreb, Croatia

Abstract

The synthesis of 2-N-benzoyl-1-(2’,3’-O-isopropylidene-5’-deoxy-β-D-erythropent-4’-enofuranosyl)isocytosine (VII) and its conversion into 5’-deoxy-α-L-lyxopentofuranosyl- (XVI) and 2-N,4’-anhydro-1-( 5’-deoxy-5’-bromo-α-L-lyxopentofuranosyl)isocytosine (XVIII), is described. Treatment of 5’-deoxy-5’-iodo- (X) or 5’-O-p-toluenesulphonyl-isocytidine (IV) with potassium phthalimide in dioxan has afforded 2’,3’-O-isopropylidene-2-N-benzoyl-2-N,5’-anhydroisocytidine (VI) in high yields.

■ Some β-Carboline Alkaloids of Ailanthus malabarica DC

Balawant S. Joshi,* Venkatesh N. Kamat, and Dilip H. Gawad

*CIBA-GEIGY Research Centre, Goregaon Bombay 400063, India

Abstract

From the bark and roots of Ailanthus malabarica DC. we have isolated and characterised eight β-carboline alkaloids of which four are new. Their structures are elucidated by spectroscopic studies.

■ Determination of Ring Stereochemistry in a Substituted Isoxazolidine by ³J (¹³C-C-C-¹H) Decoupling

John Palmer, Peter S. Rutledge,* and Paul D. Woodgate

*Department of Chemistry, University of Auckland, Private Bag 92019, Auckland, New Zealand

Abstract

The use of both ¹³C n.m.r. and ¹H n.m.r. spectroscopy, together with specific long range carbon-proton decoupling experiments has permitted assignment of stereochemistry in a substituted isoxazolidine.

■ Pteridine Studies (IV). On the Mechanism of the Conversion of 2-(Methylthio)-4,6,7-triphenylpteridine into 2-Amino-4,6,7-triphenylpteridine and 6,8-Diphenyl-1-2-(methylthio)purine

Joek Nagel and Henk C. van der Plas*

*Laboratory of Organic Chemistry, Agricultural University, De Dreijen 5, 6703 BC Wageningen, The Netherlands

Abstract

The ring contraction of 2-(methylthio)-4,6,7-triphenylpteridine (3) into 2-(methylthio)-6,8-diphenylpurine (5a) by KNH₂ in NH₃ at -33° has been studied using selectively deuterium labelled pteridines. It was found that the purine obtained from 2-(methylthio)-4,6-diphenyl-7-(pentadeuterophenyl)pteridine — prepared by phenylation of 2-(methylthio)-4,6-diphenylpteridine with pentadeuterophenyllithium — only contained 13% of the deuterium label, indicating that C-7 is mainly expelled during the ring contraction. The mechanism is discussed. Furthermore the amination of 3 was studied using bath ¹⁵N-3 labelled compounds as well as K¹⁵NH₂ in ¹⁵NH₃. It was found that the amination of 3 takes place for 50-85% — depending on [KNH₂] — according to a ring opening-ring closure mechanism (S_N(ANRORC)) forming 2-amino-4,6,7-triphenylpteridine (4). Thus in 3 the pteridine nucleus is found to be attacked by the amide ion on C-4, C-2, C-6 and C-7 in the approximate order of reactivity: C-4 > C-2 > C-7 > C-6.

■ A Stereospecific Total Synthesis of Chasmanine

T. Y. R. Tsai, Connie S. J. Tsai, W. W. Sy, M. N. Shanbhag, W. C. Liu, S. F. Lee, and Karel Wiesner*

*Natural Products Research Center, Department of Chemistry, University of New Brunswick, Bag Service #45222, Fredericton, New Brunswick, E3b 5A3, Canada

Abstract

The “aromatic intermediate” 2 was transformed by the photochemical route to the “nordenudatine” intermediate 21. Rearrangement of 21 to 22 and functionalization of this last product yielded racemic chasmanine 1.