HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Special Issue
Kyosuke Tsuda's Special Issues, Vol. 17, No. 1, 1982
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■ From Penicilin to Penem and Carbapenem. 1. Racemization of 6,6-Dibromo Secopenicillin, and Synthesis of 2-Oxo Penam Derivative
Koichi Hirai,* Yuji Iwano, and Katsumi Fujimoto
*Central Research Laboratories, Sankyo Co.,Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140 Japan
Abstract
From 6-APA the azetidinone derivative (7) which has (R)-hydroxyethyl substituent at C-6 was prepared effectively. From dibromoseco derivative (10) the same type of compounds, 17 and 18 which has (S) type substituent were prepared, however these were proved to be optically inactive dl-form. Racemization occurred during the process of the formation of the secopenicillin (10) with excess CH3I and 2.5 eq. of NaH or KOtBu in THF via the acyliminium intermediate (22). The 2-oxo penam derivative (27) was prepared from 17 as shown in Fig. 4.
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■ Reductive One-step Elimination of an Acetoxyl Residue at β-Position of a Nitro Group: Syntheses of (—)-Shikimic Acid from D-Mannose and 2-Deoxystreptamine Pentaacetate from N -Acetyl-D-glucosamine
Masayuki Yoshikawa, Yoshiharu Ikeda, Hiroshi Kayakiri, and Isao Kitagawa*
*Faculty of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Toyonaka, Osaka 560-0043, Japan
Abstract
By utilizing a reductive one-step elimination reaction of an acetoxyl residue at β-position of the nitro group in cyclitols, a synthesis of the ketocyclitol triacetate (15a), which was already converted to (-)-shikimic acid (16) and (-)-quinic acid (17), from D-mannose (4) and a conversion from N-acetyl-D-glucosamine (18) to 2-deoxystreptamine pentaacetate (22) have been accomplished.
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■ Absolute Stereostructure of Furanogermenone, a Biologically Active Sesquiterpene from Zedoariae Rhizoma
Hirotaka Shibuya, Yoshio Yamamoto, Iwao Miura, and Isao Kitagawa*
*Faculty of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Toyonaka, Osaka 560-0043, Japan
Abstract
The absolute stereostructure of a new bioactive sesquiterpene named furanogermenone (1), which was isolated from Chinese Zedoariae Rhizoma, has been determined on the basis of chemical and physicochemical evidence.
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■ Isolation and Structures of Pulchelloid A and Pulchelloid B, New Pseudoguaianolides from Gaillardia pulchella
Seiichi Inayama,* Kenzo Harimaya, Tamiko Ohkura, and Takeshi Kawamata
*Pharmaceutical Institute, School of Medicine, Keio University, Shinanomachi 35, Shinjuku, Tokyo 160-0016, Japan
Abstract
The structures of new pseudoguaianolides named pulchelloid A (1) and pulchelloid B (2) isolated from the methanol extraction of Gaillardia Pulchella together with the known pulchellin (3) and neopulchellin (4) were determined mainly by 400 MHz 1H nmr associated with decoupling experiments and 13C mr in addition to uv, ir and MS spectral data.
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■ 11-Norterodotoxin-6,6-diol and 11-Nortetrodotoxin-6-ol
Lee A. Pavelka, F. A. Fuhrman, and Harry S. Mosher*
*Department of Chemistry, Stanford University, 735 Dolores Street, Stanford, CA 94305-5080, U.S.A.
Abstract
Tetrodotoxin (1) is oxidized to 11-nortetrodotoxin-6,6-diol (2b) which is reduced to 11-nortetrodotoxin-6-ol (3); the gem-diol 2b has 20-40% and the reduction product 3 about 10% of the in vivo neurotoxicity of tetrodotoxin. The formation of the O-methyloxime of 2 has been reinvestigated.
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■ Δ3-Δ2 Isomerisations in Cephems and Their 1-Oxa Congeners
Yuji Sendo,* Mitsuru Yoshioka, and Wataru Nagata
*Shionogi Research Laboratories, Shionogi & Co. Ltd., Fukushima-ku, Osaka 553-0002, Japan
Abstract
Base-catalysed isomerisation of the 3-cephems (1a)-(1d) to their Δ2-isomers (2a)-(2d) was compared with that in the 1-oxa congeners [(1e)-(1h) →← (2e)-(2h)]. Effects of the 1-hetero atom and the 7- and 3’-substituents on the rates and the equilibrium constants in these isomerisations are discussed.
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■ Direct Phenylation of Isoxazoles Using Palladium Catalysts. Synthesis of 4-Phenylmuscimol
Norio Nakamura, Yawara Tajima, and Kiyoshi Sakai
*Central Research Laboratories, Sankyo Co.,Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140 Japan
Abstract
Several 4-phenylisoxazoles were synthesized by the palladium-catalyzed coupling of the isoxazole ring with benzene or iodobenzene. Compound 4, thus obtained, was converted to 4-phenylmuscimol (2), according to the newly developed route to muscimol (1) from 3.
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■ Stereoselective Transformation of Lycorine to Demethylungiminorine and Hippamine(2-O-Methyllycorine) to Ungiminorine
Jun Toda, Takehiro Sano, and Yoshisuke Tsuda*
*Faculty of Pharmaceutical Scicences, Faculty of Pharmaceutical Scicences, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
Ungiminorine, an alkaloid of Ungernia minor, was chemically synthesized from lycorine by the route similar to that suggested in the biosynthesis of narcissidine from galanthine. This transformation constitutes the total synthesis of ungiminorine in a formal sense.
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■ Spirocyclic Nortriterpenes from Bulbs of Scilla scilloides II. New Spirocyclic Furanoid Nortriterpenes and Related Tetranortriterpene Spirolactones
Mochammad Sholichin, Kazumoto Miyahara, and Toshio Kawasaki*
*Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Abstract
Five kinds of compounds, SSG-1 ~ -5, were isolated, besides 15-deoxoeucosterol (I), from fresh bulbs of Scilla scilloides. They were characterized respectively as 22β-hydroxy (III), 30-hydroxy (IV), 3-dehydro (V), 24,25,26-trinor-23-oxo (VI) and 24,25,26-trinor-22β-hydroxy-23-oxo (VII) derivatives of I on the basis of spectral data and by X-ray analysis for III. Although IV was identical with the compound reported by Parrilli et al, III and V are new natural products related to eucosterol (II) which was first isolated from Eucomis spp. and identified by Tamm et al. VI and VII are novel type of tetranortriterpene spiro-γ-lactones, and their coexistence with I and III is noted.
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■ Stereoselective Synthesis of (±)-10β-Hydroxyfuranoeremophilanes
Koji Yamakawa,* Tsuyoshi Satoh, and Satoshi Takita
*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Abstract
The stereoselective total synthesis of (±)-10β-hydroxyfuranoeremophilan-3,6-dione is described. The key step in this synthesis is the angular hydroxylation of 10-H-furanoeremophilan-6,9-dione using benzeneseleninic anhydride.
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■ Synthesis of the Ipecac Alkaloids from Norcamphor
Seiichi Takano,* Susumi Hatakeyama, Yoko Takashi, and Kunio Ogasawara
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
A general Route to the Ipecac Alkaloids from norcamphor (8) has been developed. Alkylation of the bicyclic lactone (9), obtained from norcamphor (8), gave the endo-isomer (10), exclusively, which was converted in four steps to the key intermediate (14). The compound (14), thus obtained, was transformed into (±)-protoemetine (2) and (±)-protoemetinol (3) via two different routes.
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■ Carbon-13 NMR Spectrum of 2’-Fluoro-2’-deoxyadenosine 3’-5’-Cyclic Phosphate
Seiichi Uesugi, Jitsuhiro Matsugi, Toshinori Kaneyasu, and Morio Ikehara*
*Faculty of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Toyonaka, Osaka 560-0043, Japan
Abstract
2’-Fluoro-2’-deoxyadenosine 3’,5’-cyclic phosphate (3) was synthesized and its 13C nmr spectrum was measured. The sugar carbon signals can be unambiguously assigned because the C(1’), C(2’) and C(3’) have different 13C-19F coupling constants. Comparison of the present data with those of other nucleoside 3’,5’-cyclic phosphates gives a definitive solution to the disputed assignment of the C(3’) and C(4’) signals for the 3’,5’-cyclic phosphate derivatives.
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■ On the Reaction of 1-Benzyl-7-acetoxy-7-methoxy-2-methyl-6-oxo-Δ4a,5,8,8a-hexahydroisoquinolines(O -Quinol Acetates) with Methanol in the Presence of Sulfuric Acid
Osamu Hoshino, Minoru Ohtani, Bunsuke Umezawa,* and Yoichi Iitaka
*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Abstract
Reaction of o-quinol acetate (1) with MeOH-conc. H2SO4 proceeded unexpectedly to give 1-(3,4-dimethoxybenzyl)-4a, 6-dimethoxy-2-methyl-7-oxo-Δ5,6,8,8a-hexahydroisoquinoline (6) and 4-methoxytetrahydroisoquinolin-6-ol (7). A brief account for the stereochemical course of the reaction was presented.
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■ A Biomimetic Synthesis of (±)-Tetrahydrotakatonine, (±)-O -Methylgigantine, and Tehaunine
Hirohi Hara, Akira Tsunashima, Hiroshi Shinoki, Osamu Hoshino, and Bunsuke Umezawa*
*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Abstract
Treatment of 7-acetoxy-7-methoxy-2-methyl-6-oxo-Δ4a,5,8,8a-hexahydroisoquinolines (6a-c) with conc. H2SO4 in Ac2O and subsequent hydrolysis followed by methylation produced the title alkaloids (9a-c), although in low yields.
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■ Reaction of 2,2,6-Trimethyl-1,3-dioxin-4-one with Schiff Base
Masayuki Sato, Hiromichi Ogasawara, Eriko Yoshizumi, and Tetsuzo Kato*
*Pharmaceutical Institute, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan
Abstract
Heating of 2,2,6-trimethyl-1,3-dioxin-4-one (1) with Schiff bases (2a-f) gave 2,3-disubstituted 6-methyl-1,3-oxazin-4-ones (4a-f). N-Benzylidene-tert.-butylamine, under the similar condition, gave acetoacetamide derivative (3g) and acetylazetidinone derivative (5).
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■ Synthesis of Brassinolide, a Plant Growth Promoting Steroidal Lactone
Masayuki Sakakibara, Katsuhide Okada, Yoshitaka Ichikawa, and Kenji Mori*
*Department of Agricultural Chemistry, Faculty of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
Abstract
Brassinolide (2α, 3α, 22R, 23R-tetrahydroxy-24S-methyl-B-homo-7-oxa-5α-cholestan-6-one) was synthesized from stigmasterol and (R)-(+)-citronellic acid.
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■ A Novel Synthesis of 1-Deazaadenosine
Tokuo Itoh,* Tomokazu Sugawara, and Yoshihisa Mizuno
*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Abstract
A novel route for the synthesis of 7-amino-3-(β-D-ribofuranosyl)-3H-imidazo[4,5-b]pyridine(1-deazaadenosine) has been developed, as illustrated in accompanying flow sheet, starting from imidazo[4,5-b]pyridine 4-oxide in much improved overall yield(20%).
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■ Synthetic Approaches toward Verrucarin A. Chiral Synthesis of (—)-Verrucarinolactone
Kiyoshi Tomioka, Fuminori Sato, and Kenji Koga*
*Faculty of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113, Japan
Abstract
(-)-Verrucarinolactone ((2S,3R)-2,5-dihydroxy-3-methylvaleric acid δ-lactone) (4) was synthesized stereoselectively from an optically active butyrolactone ((S)-γ-trityloxy-methyl-γ-butyrolactone) (6) as a chiral synthon.
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■ Sodium Borohydride Reduction of Monocyclic 1,2,3-Triazine N -Oxides
Heihachiro Arai, Akio Ohsawa, Hidefumi Ohnishi, and Hiroshi Igeta*
*School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Abstract
Reduction of 4,6-disubstituted 1,2,3-triazine 2-oxides with sodium borohydride afforded the corresponding 1,4,5,6-tetrahydro-1,2,3-triazine 2-oxides as main products. The mechanism was examined using NaBH4 in CH3OD and NaBD4 in CH3OH.
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■ A New Synthesis of 4-Methoxycarbonyloxazoles Using Diethyl Phosphorocyanidate (DEPC) and Its Application to the Synthesis of 3-Amino-4-hydroxytetrones
Yasumasa Hamada, Seiji Morita, and Takayuki Shioiri*
*Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan
Abstract
Diethyl phosphorocyanidate (DEPC) may be used for the direct C-acylation of methyl isocyanoacetate with carboxylic acids. Some of the resulting 4-methoxycarbonyloxazoles have been efficiently converted to 3-amino-4-hydroxytetrones, a class of amino reductones.
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■ Studies on Indolizine Derivatives. VI. Synthesis of Cycl[3.2.2]azinophane Derivative
Hiroshi Goto, Keiji Kurata, Hiroyoshi Awaya, Yoshinori Tominaga, Yoshiro Matsuda, and Goro Kobayashi*
*Faculty of Pharmaceutical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
Abstract
Bisindolizine derivative (10b) was obtained by the reaction of 1,4-di(2-pyridyl)butane (9) with bromomethyl t-butyl ketone. Cycloaddition reaction of 10b with methyl propiolate afforded biscycl[3.2.2]azine derivative (11b), which was reduced by lithium aluminum hydride, followed by dehydration to give unstable [2.2.2.2](1,4)cycl[3.2.2]azinophane derivative (14) .
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■ Studies on Macrocyclic Lactone Antibiotic Part IV.Biosynthectic Studies on Azalomycin F4a Using 13C-Labelled Acetate and Propionate
Shigeo Iwasaki, Keizo Sasaki, Michio Namikoshi, and Shigenobu Okuda*
*Institute of Applied Microbiology, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8567, Japan
Abstract
Incorporation of [1-13C]acetate, [1-13C]propionate and [3-13C]propionate into azalomycin F4a produced by cultured Streptomyces hygroscopicus var. azalomyceticus was studied. Fourteen molecules of acetate and 7 molecules of propionate were incorporated in the azalomycin F4a molecule.
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■ Photochemistry of 4-Pyrimidinones.VII.Reaction of Dewar 4-Pyrimidinone with Methylamine
Yoshiro Hirai, Hirotaka Kanmei, Takao Yamazaki,* and Shun-ichi Hirokami
*Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan
Abstract
Irradiation of the 2,3,6-trialkyl-4-pyrimidinones (1) and (5) in methylamine solution at 0°C gave the amidine derivatives (6) and (7). The reaction of Dewar 4-pyrimidinone (9) with methylamine in methylamine-ether gave the di-imine derivative (2) and the amidine derivative (6). The fraction of the amidine (6) increased with increasing methylamine concentration.
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■ Preparation of 1,2-Dihydro-1,2-diphenyl-1λ,2λ-diphosphorin 1,2-Disulfide
Takayuki Kawashima, Michio Shimamura, and Naoki Inamoto*
*Department of Chemistry, Faculty of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033
Abstract
1,2-Dihydro-1,2-diphenyl-1λ,2λ-diphosphorin 1,2-disulfide was synthesized from the corresponding 1,2,3,6-tetrahydro derivative by lithiation, bromination with bromotrichloromethane and dehydrobromination successively. Direct bromination of 1,2,3,6-tetrahydro derivative resulted in the P-P bond cleavage.
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■ Two New 4,5-Dioxoaporphine Alkaloids Isolated from Aristolochia tuberosa
Zhu Dayuan,* Wang Baode, Huang Baoshan, Xu Rensheng , Qiu Yunping, and Chen Xiuzhen
*Shanghai Institute of Material Media, Chinese Academy of Science, 319, Yue-yang Road, Shanghai, 200031, China
Abstract
From the roots of Aristolochia tuberosa C. F. Liong et S. M. Hwang, two new oxoaporphine alkaloids, tuberosinone and tuberosinone-N-(β-D-glucoside, were isolated, structures of which can be described as (I) and (II).
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■ A New Tremorgenic Metabolite Related to Verruculogen from Penicillium verruculosum
Masakazu Uramoto, Masato Tanabe,* Ken Hirotsu, and Jon Clardy
*Laboratoire de Synthese des Substances Naturelles, Institut de Chimie Moleculaire d’Orsay, Université de Paris-Sud, Bâtiment 410, 91405 Orsay Cedex, France
Abstract
The isolation and structural elucidation of a new tremorgenic metabolite, acetoxy verruculogen from Penicillium verruculosum is described.
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■ Heavenly Blue Anthocyanin III.Structure of Bis-deacyl Heavenly Blue Anthocyanin, a Controlled Alkaline Hydrolysis Product of Heavenly Blue Anthocyanin
Toshio Goto,* Hiroyuki Imagawa, Tadao Kondo, and Iwao Miura
*Laboratory of Organic Chemistry, Faculty of Agricultures, Nagoya University, Chikusa, Nagoya, Aichi 464-8601, Japan
Abstract
Structure of bis-deacyl heavenly blue anthocyanin was determined to be 3-O-(2-O-(6-O-(trans-3-O-(β-D-glucopyranosyl)caffeyl)β-D-glucopyranosyl)β-D-glucopyranosyl)-5-O-(β-D-glucopyranosyl)peonidine.
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■ Syntheses of Four Isomers of 25-Hydroxyvitamin D3-26,23-Lactone
Tadashi Eguchi, Suguru Takatsuto, Yutaka Hirano, Masaji Ishiguro, and Nobuo Ikekawa*
*Department of Chemistry, Faculty of Science, Tokyo Instituteof Technology, Meguro-ku, Tokyo 152-8552, Japan
Abstract
A major metabolite of vitamin D3 was recently isolated and identified as 25-hydroxyvitamin D3-26,23-lactone. To determine the configurations at C-23 and C-25 positions, the four stereoisomers were synthesized by stereoselective lactonization method. The two 23R-isomers were obtained by iodolactonization of 22,23-trans-26-acid, and the two 23S-isomers were synthesized by selenolactonization of 22,23-cis-26-acid. The four synthetic isomers and the naturally produced lactone were co-chromatographed on a high performance liquid chromatographic system capable of separating the four isomers. The natural lactone comigrated with synthetic (23S,25R)-isomer determining its structure as (23S,25R)-25-hydroxyvitamin D3-26,23-lactone.
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■ The Oxidation Reaction of Indoles with Thallium (III) Trinitrate
Takeshi Ohnuma, Hitoshi Kasuya, Youichi Kimura, and Yoshio Ban*
*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Abstract
Some indole derivatives were submitted to the oxidation with thallium (III) trinitrate [TTN] to give the corresponding oxindole and isatin derivatives. Indole-3-propionic acid derivatives were oxidized with TTN to afford the spiro-γ-lactones in good yields.
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■ Structure of Sanggenon D, a Natural Hypotensive Diels-Alder Adduct from Chinese Crude Drug “Sang-BÁi-Pí” (Morus Root Barks)
Taro Nomura,* Toshio Fukai, Yoshio Hano, and Jun Uzawa
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
From the ethyl acetate extract of the Chinese crude drug “sang-Bái-Pí” (Japanese name sohakuhi), the root barks of Morus sp. (Moraceae), a new flavanone derivative with a fused dihydrochalcone partial moiety was isolated and named sanggenon D. The structure was shown to be I on the basis of spectral data. Sanggenon D (I) is a stereoisomer at the C-14 position on the cyclohexene ring of sanggenon C (II) obtained from the same source, and is regarded biogenetically as a Diels-Alder adduct of chalcone derivative and a dehydroprenylflavanone derivative. The nmr variable temperature studies on I and II are depicted in Figures 2 and 3.