Symposium on the Chemistry of Natural Products, symposium papers
Online ISSN : 2433-1856
15
Displaying 1-50 of 54 articles from this issue
  • Article type: Cover
    Pages Cover1-
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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  • Article type: Appendix
    Pages App1-
    Published: October 01, 1971
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  • Article type: Appendix
    Pages App2-
    Published: October 01, 1971
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  • Article type: Index
    Pages A1-A5
    Published: October 01, 1971
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  • Article type: Index
    Pages A6-A12
    Published: October 01, 1971
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  • Article type: Bibliography
    Pages Misc1-
    Published: October 01, 1971
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  • N. Takamatsu, S. Inoue, Y. Kishi
    Article type: Article
    Session ID: 1
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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    A stereoselective total synthesis of optically active echinulin (1) will be discussed. To establish a method synthesizing 2, 4-(γ, γ-dimethylallyl)aniline (15) required for the synthesis of the indole moiety of echinulin (1), the acid-catalyzed amino Claisen rearrangement of N-allyl- and N-(γ,γ-dimethylallyl)aniline derivatives was examined; namely,the compounds (3), (6), (8), (11), (12), and (14) were synthesized from the corresponding N-substituted aniline derivatives. By this rearrangement, N, N-di-(γ, γ-dimethylallyl)aniline (13) was converted to 2, 4-di-(γ,γ-dimethylallyl)aniline (15) in 23% yield,which was then transformed to the gramine (21) according to Saxton's method. The gramine (21) was condensed with the diketopiperazine (22) synthesized from L-alanine. After the ester thus obtained had been hydrolyzed to the acid (24), it was heated in dioxane to afford optically active echinulin (25) (two parts) and epi-echinulin (26) (one part). The synthesized echinuline (25) was identical with natural echinulin (1) in all respects (mp, mixed mp,[α]_D, ir, nmr, etc.).
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  • Ruka Nakashima, G. P. Slater, J. C. MacDonald
    Article type: Article
    Session ID: 2
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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    Echinulin was first isolated by Quilico's group, and its structure was established by same group, except for the configuration of optical active center of tryptophan moiety. Because this group is quite easy racemize during the chemical reactions. To decide the configuration of echinulin, many physical or chemical experiments (ex. ORD, NMR., Biosynthesis, TLC. etc.) were attempted. As shown in table 2 and 3, we suceeded to determine the configuration of echinulin by ozonolysis in HCOOH-H_2O, and followed by decomposition of ozonide by H_2O_2 and acid hydrolysis (Fig.3). Amino acid analyser and microbioassay using the Leconostoc mesenteroides P-60. showed th 94% of the aspartic acid was L-form. The obtaining of the L-aspartic acid indicates the absolute configuration of echinulin were determined as shown in structure II. This result coincide with the above physical or chemical data.
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  • T. Wakamiya, T. Shiba, T. Kaneko, H. Yoshioka, T. Aoki, K. Nakatsu, T. ...
    Article type: Article
    Session ID: 3
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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    A group of tuberculostatic peptide antibiotics called tuberactinomycin (TUM) was found in the culture broth of Streptomyces griseover-ticillatus var. tuberacticus. TUM-A and B were first isolated from the broth filtrate, and a mutant prepared by treatment of the original microorganism with nitrosoguanidine produced two similar antibiotics termed TUM-N and O. Of these four congeners, TUM-B was identical with the previously known antibiotic, viomycin. The structures of two new amino acids isolated as components of TUM-A, i. e. γ-hydroxy-β-lysine and tuberactidine, were determined as reported already. On the basis of the extreme similarity of amino acid compositions as well as chemical and physical properties of four antibiotics, it is suspected that all of the peptides may have the same amino acid sequence, being only differenciated each other in existence of hydroxyl groups on residues of β-lysine and guanidinoamino acid. The chemical studies on partial hydrolyzates of these congeners suggested a possibility of a new total structure different from those proposed by other workers for viomycin, i.e. TUM-B. Finally, the X-ray analysis was performed on the crystal of TUM-O-1HC1・2HBr・3H_2O. Thus the total structure of this compound was determined evidently.
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  • Shinich Kondo, Seiji Shibahara, Shuji Takahashi, Kenji Maeda, Hamao Um ...
    Article type: Article
    Session ID: 4
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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    Negamycin (I, C_9H_<20>O_4N_4), found in 1969, is a new antibiotic isolated from the culture filtrate of Streptomyces purpeofuscus, demonstrating strong inhibition against resistant Gram-negative bacteria including Pseudomonas. We report the structure established on the basis of spectral data and chemical degradations, the synthetic work, and an interesting novel and acid-catalysed rearrangement of 1-methylhydrazinoacetic acid (VII) discovered during the structural study. The acid hydrolysis afforded a new δ-hydroxy-β-lysine (III), VII, 1, 2-dimethylhydrazine (V), sarcosine, and methylamine. The absolute configuration of I has been determined to be [2-{(3R, 5R)-3, 6-diamino-5-hydroxyhexanoyl}-1-methylhydrazino] acetic acid based on the optical property of the lactone derivative (IV). It has been shown that VII is converted into V along with sarcosine and methylamine, showing that a new rearrangement of VII took place in acidic condition. The protection of δ-hydroxy group of III with dihydropyran was found to be essential for the hydrazide synthesis of III and VII. The syntheses of VII and the antipode have successfully been carried out from D-galacturonic acid and 3-amino-3-deoxy-D-glucopyranose, respectively.
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  • Bunji Shimizu, Akira Ito, Hiromichi Saeki, Akio Saito, Eiji Ohki, Kenj ...
    Article type: Article
    Session ID: 5
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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    Leupeptin Ac-LL (1) and Pr-LL (2), metabolites of various species of Actinomycetes, was found to have an interesting anti-plasmin activity and their synthesis was already reported. This communication deals with their alternate synthesis. N^α-Cbz-N^G-NO_2-L-Arginine (3) was converted into its imidazolide (4) and reduced with LiAlH_4 to give N^α-Cbz-N^G-NO_2-argininal (5) in a good yield. The aldehyde (5) was converted into N^G-NO_2-argininal semicarbazone (8) which was coupled with an active ester of Ac-Leu-LeuOH and followed by deprotection, giving Leupeptin Ac-LL (1) in a good yield. Leupeptin Pr-LL (2) and other acyl argininals were also synthesized in a similar manner. In addition, N^α-(Ac-Leu-Leu)-N^G-Cbz-L-arginine δ-lactam (22) was treated with LiAlH_4 to give the corresponding aldehyde (23), which were deprotected, affording 1 in a good yield. Leupeptins (1 and 2) thereby obtained exhibited antiplasmin activities similar to the samples of natural origin. On the other hand, Ac-Leu-Leu-D-argininal, which was analogously synthesized from N^α-Cbz-N^G-NO_2-D-arginine, the enantiomer of 3, was found to have practically no activity.
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  • Mitsuhiro Kinoshita, Shimpei Aburagi, Masao Wada, Sumio Umezawa
    Article type: Article
    Session ID: 6
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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    The first total synthesis of antifungal antibiotic antimycin A_3 (blastmycin) in a form of diastereomeric mixture was reported in 1969 from our laboratory. We have now synthesised the natural antimycin A_3 (1). The modified Reformatsky reaction of 2-benzyloxypropanal with t-butyl 2-bromo-hexanoate afforded the mixture of the diastereomeric t-butyl 4-benzyloxy-2-hutyl-3-hydroxypentanoate which contained ca. 55% of the major racemic diastereomer (2). The chromatographically separated fraction consisting of 2 contaminated by a small amount of the minor diastereomer was O-isovalerylated. The product was purified by silica gel column chromatography to give the O-acylated derivative of 2, which was hydrogenolyzed to afford t-butyl 2-butyl-4-hydroxy-3-(isovaleryloxy)pentanoate (3). Condensation of 3 with N-benzyloxycarbonyl-O-t-butyl-L-threonine yielded two kinds of diastereomeric t-butyl 4-(N-benzyloxycarbonyl-O-t-butyl-L-threonyloxy)-2-butyl-3-(isovaleryloxy)pentanoate. The less polar (+)-diastereomer (4) of the two was separated by silica gel column chromatography of the mixture. Lithium aluminium hydride reduction of 4 followed by hydrolysis and O-isovalerylation afforded the (+)-blastmycinone which was identified with the natural blast-mycinone obtained by mild alkaline degradation of blastmycin (antimycin A_3). De-t-butylation of 4 followed by cyclization with trifluoroacetic anhydride in benzene afforded the intramolecular cyclization product, 3-benzyloxycarboxamido-7-butyl-4, 9-dimethyl-1, 5-dioxa-8-(isovaleryloxy)cyclononane-2, 6-dione (5). Removal of the N-protecting group of 5 followed by N-acylation with O-benzyl-3-nitrosalicylic acid N-hydroxysuccinimide ester yielded 3-(O-benzyl-3'-nitrosalicylamido)-7-butyl-4, 9-dimethyl-1, 5-dioxa-8-(isovaleryloxy)cyclononane-2, 6-dione (6). The product (6) was again hydrogenolyzed and then N-formylated to afford the final product, antimycin A_3 (1).
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  • U. Nagai, Y. Fujii, T. Umemura, M. Kurumi
    Article type: Article
    Session ID: 7
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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    ORD-spectra of DNP-amino acids have two distinct features. The first is that all the DNP-amino acids so far measured showed very strong rotation near 220nm, especially in 4%-NaHCO_3aq. The big rotation was applied to know the configuration and further the D:L-ratio of amino acids, in a very small scale, and the hydrlysate of Gramicidine S was analyzed successfully. The second feature is that some DNP-amino acids have strong Cotton effect in their visible region spectra. They all have two DNP-chromophores in a molecule except DNP-phenylalanine. This interesting behaviour can be attributed to some interaction between the two DNP-chromophores. Similar phenomena are found in cases of steroid dibenzoates reported by K. Nakanishi et al. and of dinucleotides pointed by I. Tinoco, Jr. et al. If the strong Cotton effect means the spatial proximity of the two DNP-chromophores, it can be applied to the conformational analysis of peptides. Bis DNP-gramicidine S was prepared and showed a strong Cotton effect in the same region of its ORD spectrum. The conformation having the two delta-amino groups of the ornithine residues near enough to effect mutual interacion is suggested to be probable on the basis of this result, and is consistent with that proposed for Gramicidine S by L. C. Craig et al. and by R. Schwyzer et al.
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  • K. Koga, K. Achiwa, T. Shioiri, T. Kitagawa, Y. Takeuchi, Chin C. Wu, ...
    Article type: Article
    Session ID: 8
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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    It has been previously shown that phenylalanine is a precursor of tropic acid (I) in Datura Stramonium plants. We have found that tropic acid is formed from phenylalanine or its ethyl ester by its chemical deamination with nitrous acid through 1, 2-migration of phenyl group (T. L., 1967, 3007; 1971, 2283, 2287). For the extension of this work, atropine and apoatropine were obtained by the deamination of IV with sodium nitrite in dilute sulfuric acid. When L-phenylalanine was deaminated with sodium nitrite in trifluoroacetic acid, S(-)-tropic acid which shows the same absolute configuration with natural tropic acid, was obtained, on the other hand, the deamination of L-phenylalanine ethyl ester gave antipodal R(+)-tropic acid.
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  • Shujiro Seo, Ushio Sankawa, Yukio Ogihara, Shoji Shibata
    Article type: Article
    Session ID: 9
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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    Previously a structural formula (V) was proposed for flavoskyrin, a yellow pigment of Penicillium islandicum Sopp. NRRL 1175. In relation with the revised structure of rugulosin (I) and luteoskyrin (II), the structure of (-) flavoskyrin has been reexamined. Flavoskyrin has now been found to be a dimeric compound having a molecular formula, C_<30>H_<24>O_<10>. On treatment with thionyl chloride in pyridine (-) flavoskyrin is converted into (+) dianhydrorugulosin ((+) dichrysophonol (8, 8')). By the action of pyridine (-) flavoskyrin affords dianhydrorugulosin and (-) rugulosin. The synthetic compounds (VIII), (XII) and (XIII) which were used as the model compounds for flavoskyrin have now been proved by the Mass and MNR spectra to be dimers. The comparative studies using UV, IR, NMR and Mass spectra have led the new structure XVIa for flavoskyrin. The mechanism of dimerization reaction of the synthetic model compoumds has also been discussed.
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  • R. Miura, J. Okada, T. Ohno, M. Nakazaki
    Article type: Article
    Session ID: 10
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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    When aromatic hydrocarbon is administered into a mammal, it is oxidized and excreted in urine partly as the optically active trans-dihydroxydihydro derivative. The knowledge of its absolute configuration is crucial for the study of chemical carcinogenesis as well as detoxication mechanism. We wish to report the absolute configurations of optically active trans-dihydroxydihydro metabolites of acenaphthylene and indene. (+)-trans-1, 2-Dihydroxyacenaphthene (I)a was obtained from the urine of rabbits, which had been injected subcutaneously with acenaphthylene. (+)-(I)a was acetylated with acetic anhydride and pyridine to give (-)-trans-1, 2-diacetoxyacenaphthene (I)b. Exhaustive ozonolysis of (-)-(I)b was carried out in acetic acid. The reaction product was treated with p-bromophenacyl bromide to afford (+)-di-O-acetyl di-p-bromophenacyl tartrate (V), which was found to be the derivative of (-)-tartaric acid. This fact indicates that (+)-(I)a has the 1R, 2R-configuration. (+)-trans-1, 2-Dihydroxyacenaphthene (I)a was converted to (-)-dibenzoate (I)c with benzoyl chloride and pyridine. Semiempirical calculation based on exciton theory was applied to the CD of (-)-(I)c, which confirmed the 1R, 2R-configuration of (+)-(I)a. The optical resolution of racemic trans-1, 2-dihydroxyindane (II)a via dimenthoxyacetate gave (-)-(II)a. Acetylation of (-)-(II)a with acetic anhydride and pyridine afforded (-)-trans-1, 2-diacetoxyindane (II)b. After exhaustive ozonolysis of (-)-(II)b in acetic acid, the reaction product was treated with diazomethane and column chromatography on silica gel afforded (+)-dimethyl threo-2, 3-diacetoxy-glutarate (VI), which was identified as the derivative of (-)-tartaric acid. This result means that (-)-(II)a has 1R, 2R-configuration, consequently its enantiomer (+)-(II)a, the metabolite of indene in rats, has 1S, 2S-configuration.
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  • T. Tomimatsu
    Article type: Article
    Session ID: 11
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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    A new coumain derivative, C_<20>H_<22>O_4, mp 93-94°, was isolated from the root of Poncirus trifoliata Rafi. It was named poncitrin, and hydrogenated to give tetrahydroponcitrin. Poncitrin and tetrahydroponcitrin have been investigated by means of the nuclear magnetic resonance spectroscopy, and of the nuclear Overhauser effect measurments. It was suggested that the structure of poncitrin corresponds to be (3). A further experiments have been carried out by chemical degradations of poncitrin and its derivatives. Hydrogenation of poncitrin proceeded stepwise to give tetrahydroponcitrin (15) and hexahydroponcitrin (16), respectively. Degradation of (15) with aqueous sodium hydroxide and methyl sulfate resulted in O-methyltetrahydroponcitrinic acid (17). Catalytic hydrogenation of (17) gave the corresponding dihydro derivative (18). Degradation of (16) under the same conditions as the degradation of (15) also afforded (18). However, degradation of (3) under the same conditions as the degradations of (15) and (16) gave trans-cycloponcitrinic acid(19a) or the mixture of trans- and cis-cycloponcitrinic acid (19a and 19b). Hydrogenation of either 19a, or 19a and 19b yielded cyclotetrahydroponcitrinic acid (20). Permanganate oxidation of (3) produced a-hydroxyisobutyric acid which indicated the presence of a 2, 2-dimethylchromene ring in the molecule. Hydrolytic fission of (3) resulted in a phloroglucinol derivative. Treatment of (20) with hydrobromic acid gave compound (21). These data indicate that the structure of poncitrin is that of formula (3).
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  • Teruo Matsuura, Tadashi Takemoto, Ruka Nakashima
    Article type: Article
    Session ID: 12
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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    A novel photorearrangement of 3-hydroxyflavones (I) leading to 3-aryl-3-hydroxy-1, 2-indandiones (II) is described. Irradiation of 3-hydroxy-2'-methoxyflavone (Ia) in benzene-isopropyl alcohol with ultraviolet light (>290nm) gave a crystalline isomer, 3-hydroxy-3-(2'-methoxy-phenyl)-1, 2-indandione (IIa), the structure of which was confirmed by a synthesis of its phenylenediamine adduct (IIIa). Under similar conditions, 3-hydroxyflavone (Ib), 3-hydroxy-4'-methoxyflavone (Ic) and 3-hydroxy-5, 7, 3', 4'-tetramethoxyflavone (Id) gave corresponding 3-aryl-3-hydroxy-1, 2-indandiones, IIb, IIc and IId, respectively, which were characterized as o-phenylenediamine adducts, IIIb, IIIc and IIId. Quercetin (Ie) was recovered unchanged under these conditions. On irradiation under nitrogen 3-methoxyflavone (VI) gave a dehydrocyclization product VII. Possible mechanisms for this photorearrangement are discussed in term of the formation of 3-aryl-2, 3-epoxy-2-hydroxy-1-indanone intermediate IX.
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  • Yoshihiro Sato, Yukiko Sakamoto, Toshiko Seki, Sayoko Shoda
    Article type: Article
    Session ID: 13
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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    The dynamic aspects of the biosynthesis and metabolism of griseofulvin were elucidated on Penicillium urticae by isotopic techniques. At first, ^<14>C-2-CH_3CO_2Na was added at a definite time to the fermentation broth (growing cells) of P. urticae, and after culture of further 24hr. or at the end of 12th day, the neutral and acidic metabolites were isolated by the usual procedures. The metabolites were analyzed by the liquid scintillation counting, radio gas chromatography, or auto-radiography of TLC. The results indicated that ^<14>C-2-CH_3CO_2Na was incorporated into ergosterol mainly at the 5th day and into griseofulvin at the 7th to 11th days. The important result is the increase of total radioactivity of griseofulvin in the mycelium and the decrease of that in the filtrate, by analyses of radio activities. Further evidence of the above results was supplied by experiments using ^<14>C-griseophenone C as a precursor of griseofulvin. Consideration of these results indicates that griseofulvin is metabolized while it is biosynthesized, which is recognized as only secondary metabolite.
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  • Seisho Tobinaga, Eiichi Kotani, Naoki Takeuchi, Masayuki Murase
    Article type: Article
    Session ID: 14
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    A new method for the intramolecular oxidative coupling and intermolecular oxidative coupling by a new iron complex [Fe(DMF)_3Cl_2][FeCl_4] prepared from ferric chloride and dimethylformamide (DMF) which gives the oxidation products in high yield under mild condition and which avoids the formation of polymeric compounds in minimum amounts, was investigated. A. Synthesis and characterization of a new iron complex: The iron complex was synthesized from ferric chloride and DMF in ether in yield 95.5%. The molecular formula for this complex was reduced to [Fe(DMF)_3Cl_2][FeCl_4] by the visible light absorption spectrum (Fig. 1). B. Intramolecular oxidative coupling reactions: Oxidation of the type of compound 1 by a new oxidizing reagent was investigated. Oxidation of 1 (R_1=R_2=OCH_3); (R_1=OCH_3, R_2=H); and (R_1=R_2=H) gave the corresponding dienones 2 in yield 67%, 67%, and 39%, respectively. C. Intermolecular oxidative coupling reactions: Pummerer's ketone 3 from p-cresol, the dilactone 4 from ferulic acid and the unsymmetrical dimer 5 from methyl indole-3-acetate were obtained by the oxidation using a new oxidizing agent in yield 28%, 35% and 50%, respectively.
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  • Hiroshi Irie, Shohei Tani, Hiroyuki Yamane
    Article type: Article
    Session ID: 15
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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    Rhoeadine (I), which occurs in a variety of plants of the genus Papaver of the Papaveraceae, is an alkaloid of the group characterized by its 3-benzazepine structure. In connection with our synthtic studies of ochotensine and related alkaloids, we have worked out a route to rhoeadine starting from the intermediate (VII) for the synthesis of ochotensine and applying a Wagner-Meerwein rearrangement which resulted in enlargement of the isiquinoline ring. The spiro-isoquinoline (VII) was treated with ethyl chloroformate and triethylamine to give the urethane (XX). This was methylenated with methylene iodide and potassium carbonate in dimethyl sulphoxide to furnish the dimethylene-dioxy-spiro-isoquinoline (XXI). Treatment of this with lithium aluminium hydride gave the N-methylamino-alcohol (XXII). The alcohol (XXII) was treated with methane sulphonyl chloride and triethylamine in dry tetrahydrofuran to give a mixture of unsaturated amines (XXII) and (XXIV). Oxidation of the allylamine (XXIII) with osmium tetroxide gave the diol (XXV). Treatment of (XXV) with sodium metaperiodate followed by sodium borohydride, gave (±)-rhoeagenine diol (V), m.p. 142-143°whose i.r. (CHCl_3), Mass and n.m.r. spectra were superimposable upon those of rhoeagenine diol from natural sources. The same sequence of reactions starting from dimethoxy-spiro-isoquinoline (XXIX) gave the α-glycol (XXXIII) which was subjected to oxidation with periodate followed by reduction with lithium perhydro-9b-boraphenalylhydride to yield alpinigenine diol (XXXV). The diol (XXXV) was converted to alpinigenine (III) by oxidatione with manganese dioxide.
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  • Y. Tsuda, K. Isobe, A. Ukai
    Article type: Article
    Session ID: 16
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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    Several 3-Aryl-4, 5-dioxo-Δ^2-pyrrolines were newly synthesized and found to be a sufficient dienophile to prepare angularly substituted cis-fused hydro-indoles. The method thus opened the way to synthesize various natural alkaloids having spiro-structure. By application of this method, the title alkaloids were synthesized as follows. Starting from piperonyl cyanide the key intermediate (14) was prepared by 3 steps via controlled hydrogenation (40Kg/cm^2 and 70°) of cyanopyruvate (10). Treatment of (14) by NBA, then with base afforded epoxy-ketone (33) which on BF_3-etherate in methanol gave (34) as a major product. LAH reduction of (34) gave stereospecifically a diol (36), which is common intermediate of the title alkaloids. Pictet-Spengler cyclization of (36) by HCHO-AcOH yielded (37) which on tosylation and detosylation with DBU gave (±)-haemanthamine (42). Bischler-Napieralsky reaction of the formate (43) by POCl_3 gave 6-hydroxy derivative (44) which on methylation followed by alkaline treatment gave (45). Tosylation and detosylation of (45) gave (±)-tazettine (46). While (44) was smoothly oxidized by MnO_2 to a lactam which could be converted to (47) as above. Short reduction of (47) with LAH gave (±)-haemanthidine (48). The identities of the synthetic specimens were confirmed by comparisons of i.r. and n.m.r. spectra, and t.l.c. with natural alkaloids.
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  • T. Kametani, K. Fukumoto, S. Shibuya, M. Ihara, M. Koizumi, T. Kohno, ...
    Article type: Article
    Session ID: 17
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    The organic photolytic reaction provides an efficient method in a few steps for the synthesis of the strain compounds and the complicated compounds, which are difficult to obtain by a classic reaction. Therefore, we examined a synthesis by photolytic reaction of several alkaloids having complicated structure. Photolysis of the diazotized 1-benzylisoquinolines gave the aporphine and morphinandienone alkaloids. Moreover, the 1-phenethylisoquinoline series afforded the homo-aporphine and homomorphinandienone alkaloids. Secondly, photolysis of several types of phenolic bromo-compounds furnished the aporphine, morphinandienone, proaporphine, proerythrinadienone, hasubanan related compound, homoaporphine, homomorphinandienone, homoproaporphine and Amaryllidaceae alkaloids.
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  • Y. Kishi, M. Aratani, H. Tanino, T. Fukuyama, F. Nakatsubo, T. Goto, S ...
    Article type: Article
    Session ID: 18
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    A stereospecific synthesis of an equivalent of 9-deoxytetrodotoxin will be discussed. The ether alcohol (6), a key intermediate in this study, was stereospecifically synthesized from readily available 5-acetyltoluhydroquinone (2) by eight steps. The ether alcohol (6) was converted to the ketone (15), which was then subjected to Baeyer-Villiger rearrangement to afford the seven membered lactone (16) quantitatively. The seven membered lactone (16) was transformed to the amine (24) by eight steps. The amine thus obtained was converted to the diacetyl guanidine derivative (27) through the N-acetyl ethylisothiourea derivative (26). From the diacetyl guanidine derivative (27), 3-formyl-9-deoxytetrodotoxin acetate (28) was synthesized by a treatment with aq. trifluoroacetic acid, followed by periodate oxidation. A method introducing a hetero atom into the C_9-position of some intermediate will be discussed together. After the ketone (15) had been brominated by pyrrolidone hydrotribromide, it was subjected to Baeyer-Villiger rearrangement to afford the seven membered lactone (30), which was then transformed to the six membered lactone (31) by ethanolic acid.
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  • J. Yoshimura, T. Iida, K. Sato, H. Wakai, T. Sekiya
    Article type: Article
    Session ID: 19
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    A synthetic plan of tetrodotoxin from D-glucose was made and its key-problems were previously examined. The plan is roughly composed of (1) introduction of hydroxymethyl group at C_3 of D-glucose, (2) introduction of a protected aldehyde or an equivalent group instead of the C_5-hydroxyl group, (3) conversion of C_6-hydroxyl group to nitro group and followed by cyclization between C_1 and C_6, (4) condensation of glyoxylic acid at the position of nitro group of the resulted nitro-cyclohexanol, and (5) conversion of the nitro group to guanidine group and followed by cyclization with the aldehyde group protected, and following results were obtained for these problems. (1) 1, 2;5, 6-Di-O-isopropylidene-3-C-hydroxymethyl-α-D-glueofuranose (13) was successfully obtained by condensation of 1, 2;5, 6-di-O-isopropylidene-α-D-ribo-hexofuranos-3-ulose with diazomethane and followed by treatment with alkali, or by treatment of the corresponding 3-C-methylene derivative with permanganate, and the configuration at C_3 of 13 was throughly proved. (2 and 3) Introduction of nitromethyl group at C_5 was accomplished by reaction of nitromethane with 3-O-benzyl-1, 2-O-isopropylidene-6-O-trityl-α-D-xylo-hexofuranos-5-ulose or 3-O-acetyl-5, 6-dideoxy-1, 2-O-isopropylidene-6-C-nitro-α-D-xylo-hexofurano-5-enose as model compounds, and cyclization of them are now undertaking. (4 and 5) The facts that glyoxylic acid condensed with 2-nitrocy-clohexanol and that 2-deoxy-2-guadidino-D-glucose exists as D-glucofurano[1', 2';4, 5]-2-imino-imidazolidine or 2-imino-4-(D-arabo-tetrahyd-roxybutyl)-imidazole supported the above mentioned plan.
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  • T. Kosuge, H. Zenda, A. Ochiai, N. Masaki, M. Noguchi, S. Kimura, H. N ...
    Article type: Article
    Session ID: 20
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    A new marine toxine, surugatoxin was isolated from a carnivorous gastropod, Babylonia japonica captured in Suruga Bay. This paper deals with isolation and chemical structure of surugatoxin. Surugatoxin evokes a mydriasis in mice like atropine, at a minimum dose of 0.1μg/g body weight, and is quite unstable against acid, alkaline and heat. Surugatoxin has following properties; colorless prisms, mp>300℃, C_<25>H_<26>N_5O_<13>Br, UV λ^<H_2O>_<max> mμ(ε) 276 (14,000), IR υ^<kBr>_<max> cm^<-1> 3200, 1740 (sh), 1695, 1640. Degradation of surugatoxin with 1N-hydrochloric acid or 2N-ammonium hydroxide at 100C afforded one mole ratio of myo-inositol. The chemical structure of surugatoxin was determined as (II) by X ray analysis.
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  • Y. Ban, T. Ohnuma, Y. Sendo, T. Sato, M. Nagai, T. Oishi
    Article type: Article
    Session ID: 21
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    The order (corynanthe→strychnos→aspidosperma→iboga) in the biosynthesis of indole alkaloids with a close relationship to iridoid glucosides as the precursors has been recently established. In connection with this biosynthetic pathway, an attempt to synthesize these alkaloids from the common intermediate has been extensively made in our laboratory. As a recent successful example, the entitled compound and the relatives have been synthsized in line with this principle. It was previously reported by us that the condensation of 2-hydroxytryptamine hydrochloride (7) with formylacetone ethyleneketal (8) provided the spiro-oxindoles (9a, b), both of which were converted to (10) as a single product. Thus, the iminoethers (17a, b, c) were prepared from (9a, b) via (15a, b), and isolated as three stereoisomers, two (17a, b) of which were cyclized with NaH in DMSO to the pentacyclic derivatives in two isomerides [19a, m.p. 247-249°, δ4.32 (d. J=8.2Hz, C_<19>-H) and 19b, m.p. 230-232°, δ4.02 (d. J=11Hz, C_<19>-H)]. The former (19a) was converted by a chain of reactions of LiAlH_4 reduction, acetylation, and then hydrogenation into Na-acetyldesethylaspidospermidine (21a, IR 2800 and 2740cm^<-1>; NMR (CDCl_3) δ2.24 (s, CH_3CO), 4.40 (q, C_2-H) as a resin (picrate, m.p. 147-150°), which was identified with the product obtained on the Fischer indolization of heating the phenylhydrazone (26, A/B trans) with acetic acid for many hours, followed by reduction and acetylation. The stereochemistry of this compound might be presumed to be identical with that of the natural alkaloids based on the above NMR spectral data, because the C_2-H signals of these alkaloids appear atδ4.5-5.0 (quartet) and are well known as 'aspidosperma finger print', which are remarkably different from the corresponding signal (δ4.92 as a triplet) of "dl-pseudo-(C/D trans)-aspidospermine" synthesized by us. On the other hand, the ketone (10) was reduced with NaBH_4 in i-PrOH to (28) as two isomers, (28a, m.p. 215°) and (28b, m.p. 199-201°). The former (30a) was transformed into the amide [31, m.p. 153-154°; IR υ^<nujol>_<max> 1728, 1640, 1358 and 1169 cm^<-1>; Mass (m/e) 472, 474(M^+)] through tosylation, deacetylation and acylation with β-chloropropionyl chloride. The acrylamide (32) which was obtained by treatment of (31) with K_2CO_3 in ethanol, was cyclized with the Meerwein's reagent in dichloroethane to the lactam [12, m.p. 203-204°, IR υ^<nujol>_<max> 1718, 1638, 1357 and 1168 cm^<-1>; λ^<EtOH>_<max> 257mμ; Mass (m/e) 436 (M^+), which was identified with the product obtained from (19a) by NaBH_4 reduction, tosylation and oxidation with Jones' reagent. Quite similarly, (30a) was converted into the lactam as two stereoisomers [34a, m.p. 191-193°; IR, υ^<EtOH>_<max> 1728, 1645, 1365 and 1172 cm^<-1>; UV, λ^<EtOH>_<max> 257mμ m: Mass (m/e) 464 (M^+), and 34b, m.p. 228-229°; Mass (m/e) 464 (M^+)], a mixture of which on account of scantiness of the quantity, was led to the ethylenethioketal (m.p. 225.5-227°, colorless prisms, Mass (m/e) 540 (M^+). The thioketal was transformed into 7-ethyl-5-des-ethylaspidospermidine (35) in the sequential processes of desulfurization with Raney Nickel, LiAlH_4 reduction and acetylation, the infrared spectrum of (35) is almost identical with that of the corresponding material derived from the natural alkaloid by Kutney. Thus, a series of oxindole derivatives have been transformed into aspidosperma skeltons in two different ways. The relationship between oxindoles and indole alkaloids in biosynthesis is being investigated in connection with the present work.
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  • N. Aimi, E. Yamanaka, J. Endo, S. Sakai, J. Haginiwa
    Article type: Article
    Session ID: 22
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    Though the general methods of oxidative conversion of 2, 3-disubstituted indolic alkaloids to 3, 3-disubstituted oxindoles are well known, the reverse changes have been realized only in a few, rather simple oxindoles by use of strictly controlled amounts of LiAlH_4. In our structural study of gardneramine (12), NaBH_4 in acetic acid was found to be a good reducing reagent of iminoether to dihydro derivative (13). When this procedure was applied to the iminoethers derived from uncarines C and E, isorhynchophylline and yohimbine, the corresponding 3-monosubstituted indoles 22, 24 and 25 were formed. Obviously, two step reduction took place through an iminium intermediate (A) as shown in chart 5. Then the indoles, thus obtained, were subjected to the oxidative cyclization using Hg(OAc)_2 to form natural indolic alkaloids. Thus, tetrahydroalstonine (28) and akuammigine (29) were formed in approximately equal amounts from 22. Hirsutine (31), though in poor yield, was obtained from 24. Compound (25) afforded pseudoyohimbine as a main product along with yohimbine (1).
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  • K. Oka, Y. Ike, H. Kinoshita, S. Hara
    Article type: Article
    Session ID: 23
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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    The results of the synthetic studies on several steroidal alkaloids of salamander and frog venoms were presented. (1) Cycloneosamandione (VIII) and Cycloneosamandaridine (IX) Recently, the early proposed structure of cycloneosamandione (VI), which had been determined by G. Habermehl with the X-ray diffraction method, has been revised to be VIII on the basis of his own synthetic work. In order to reconfirm this structure, the compound VIII was synthesized by the sequre synthetic sequence. As a result, the physical data of the synthetic specimen were consistent with those of the natural product. Cycloneosamandaridine has been known as one of the minor constituents of the salamander alkaloids. Since this alkaloid has been recognized to have the identical skeleton with cycloneosamandione, the structure, we suppose, should be also revised to be IX from VII. Consequently, we have synthesized the compound IX via the same intermediate 16 as the synthesis of cycloneosamandione (VIII). The identification of our synthetic product with the natural one is now in progress. (2) Batrachotoxin (XI) The synthesis of batrachotoxin has been attempted. The treatment of the hemiacetal 27 with aminoethanol followed by reduction afforded a mixture of 18-hydroxyethylamino steroids (28a and 28b). Then the mixture was converted into the enone 36, which might serve as an useful intermediate for our purpose.
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  • Ko Kaneko, Mikako Watanabe, Shigenori Taira, Yuhsuke Kawakoshi, Hideo ...
    Article type: Article
    Session ID: 24
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    It was found that the etiolated Veratrum grandiflorum Losen. fil. accumulated solanidine glycoside in the leaf and subsequently, when the etiolated plant was illuminated, the accumulated solanidine glycoside was converted gradually to jerveratrum alkaloid. It seems reasonable to accept that, at the budding period and in the early stage of etiolation, the veratrum plant probably accumulates important precursors which are converted rapidly to solanidine under etiolated condition. On the other hand, when the etiolated plant is illuminated, it seems to remain some intermediates of the reaction of C-nor-D-homo rearrangement from solanidanine alkaloid to jerveratrum alkaloid. At the first point, etioline (22, 26-iminocholesta-5, 22(N)-diene-3β, 16α-diol) was isolated as major alkaloid from the budding veratrum plant and its structure was determined by its physical and cheimical properties. It appears that etioline is located on the rout of solanidine biosynthesis from cholestene derivatives. The hydroxylated solanidine was isolated from the leaf and rhizome of veratrum plant which was illuminated during the relatively short times after etiolated culture. Its structure was determined as 12β-hydroxy-rubijervine (epirubijervine) by molecular rotation. This alkaloid was named illuminine and it was assumed to be the inducing substance in the reaction of C-nor-D-homo rearrangment in veratrum plant.
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  • M. Funamizu, K. Nakanishi, N. Furutachi, A. Terahara, S. Blobstein, A. ...
    Article type: Article
    Session ID: 25
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    Yeast phenylalanine tRNA contains a fluorescent base adjacent to its anticodon. This base has attracted the interest of a great many workers in view of its significant role and fluorescence, but scarcity of material had prevented its structural elucidation. We have been able to propose a structure on the basis of spectroscopic properties obtained with ca. 300μg of material and model syntheses. The proposed structure has now received full support by a total synthesis of the racemic Y base. Moreover, the absolute configuration has been established by ozonolysis of a natural Y base to a compound which in turn has been prepared from S-(+)-glutamic acid. In addition, the rare hydroperoxide containing structure has been forwarded for a similar fluorescent base contained in livers of rat, calf, beef, chicken and in wheat germ. Presence of this hydroperoxy-Y also had already been noted by many workers, but nothing was known pertaining to its structure.
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  • Masato Tanabe, Hugh C. Barrett, Takashi Hamasaki, Haruo Seto, Yoshiyuk ...
    Article type: Article
    Session ID: 26
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    Biosynthetic studies on microbial metabolites have been greatly simplified by the use of carbon-13-labeled precursors and carbon magnetic resonance (cmr) for detection and facile identification of the labeling patterns in the metabolite without recourse to chemical degradation. Our initial biosynthetic studies employed continuous wave cmr with proton noise decoupling at 25.15MHZ with 50 to 1500 spectral accumulations and acquisition times of 2 to 72hr, depending on the quantity and enrichment levels of the sample. Enhanced sensitivity by an order of magnitude results from the use of FT techniques in cmr, with appreciable benefits in shorter spectral acquisition times and/or smaller sample requirements. Application of FT cmr to unambiguously define the biosynthetic origin of all carbon atoms of the fungal metabolites, avenaciolide, aspyrone, and rubratoxin B, is presented. Also discussed is the first application of FT-cmr at 55.33MHz, which verifies the unique J^<13>C-^<13>C observable between C_9 and C_<15> in an enriched sample of sterigmatocystin.
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  • T. Suga, Y. Asakawa, N. Iwata
    Article type: Article
    Session ID: 27
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
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    Chemical constituents of Alnus sieboldiana which belongs to the same genus as A. pendula has been reported previously by the present authors. We now examined the isolation and structural elucidation of chemical constituents of A. pendula and the comparison between these plants from the viewpoint of chemotaxonomy. From the benzene extract of the viscous material of the catkin, a new ketone, 1, 7-diphenyl-1, 3-heptadien-5-one (m.p. 61.0-62.5℃), n-paraffins (C_<21>-C_<31>), α-olefines (C_<23>-C_<29>), β-amyrenone, taraxerone, cinnamaldehyde, benzylacetone, β-phenylethyl cinnamate, pinocembrin, pinostrobin, alpinetin, galangin, pinosylvin monomethyl ether, eugenol, chavicol, benzoic acid, cinnamic acid, and β-phenylpropionic acid were identified. All aromatic compounds isolated from A. peneula have one or two monosubstituted benzene ring as well as those of A. sieboldiana. This seems to indicate that these compounds were biosynthesized from routes of shikimic acid-cinnamic acid and shikimic acid-malonic acid.
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  • Hiroaki CHIKAMATSU, Werner HERZ
    Article type: Article
    Session ID: 28
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    We have extended our systematic study of the genus Iva (Compositae, Heliantheae, subtribe Ambrosiinae) to Iva dealbata Gray, whose distribution is limited to west Texas and New Mexico. In the present paper, we discuss the structure of ivalbatin, a new sesquiterpene lactone from this species. Ivalbatin, C_<15>H_<20>O_4; [α]^<29>_D-84°, which easily polymerized to give an insoluble gum in ordinary solvents, was acetylated to furnish crystalline acetate (3), C_<17>H_<22>O_5; m.p. 128-128.5°; [α]^<20>_D-136°. A Michael adduct (8) obtained by the treatment of (3) with MeONa-MeOH, was acetylated to give crystalline acetate (9), C_<18>H_<26>O_6; m.p. 90-91°. (8) was dehydrated with MsCl-pridine or TsCl-lutidine to give a diene product (10). C_<16>H_<22>O_4; b.p. 130-140°/0.001 mmHg. The structure of ivalbatin has been established as (2) on the basis of the chemical and spectral data of (3), (9), and (10). The R-configuration of the asymmetric center at C-9 shown as (26) was determined by the Horeau method. The absolute configuration of ivalbin (1) which had been previously isolated from the same plant, is also discussed.
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  • Masahiro Tada, Hajime Nagano, Eiichi Shirasaki, Hideo Komatsu, Yoshiak ...
    Article type: Article
    Session ID: 29
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    Three new furanoeremophilanes were isolated from Ligularia japonica Less., and their structures determined as furanoeremophilane-6β, 10β-diol (I), 10β-hydroxy-6β-methoxyfuranoeremophilane (II) and 10β-hydroxyfuranoeremophilan-6β-y1 2'ζ-methylbutanoate (III), respectively. Two new sesquiterpenes isolated from Farfugium japonicum Kitam. (=Ligularia tussilaginea Makino) were shown to be a tetrahydronaphtofuran derivative (V) and a benzofuran derivative (VI), respectively.
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  • Narihiko Fukamiya, Michiharu Kato, Hisashi Uda, Akira Yoshikoshi
    Article type: Article
    Session ID: 30
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    Seychellene (1), a sesquiterpene isolated from patchouli oil, was synthesized in racemic form by applying the intramolecular Diels-Alder addition of a monocyclic cyclohexadienone derivative as the key step. Dimethylcyclohexenone (13) was alkylated with 3-methyl-1, 5-diiodopentane in liquid ammonia using sodium amide as the base giving iodoketone (28). The reaction of two molar equiv of NBS on (28) afforded bromocyclohexadienone (33) in a moderate yield. Treatment of the latter with chromous chloride led to deconjugated ketone (35), which was then converted to conjugated ketone (34) by an acid. Treatment of (34) with dimethylamine followed by oxidation of the resulting aminoketone (36) with hydrogen peroxide gave N-oxide (37). Pyrolysis of the N-oxide caused a Cope elimination and the concurrent Diels-Alder addition of the elimination product (6) giving an adduct (7a). Hydrogenation of (7a) afforded norseychellanone (5), which has been reported to be transformed into seychellene (1).
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  • I. Nagakura, H. Ogata, S. Yokomori, S. Maeda, Y. Kitahara
    Article type: Article
    Session ID: 31
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    Starting from 2-methyl-cyclohex-2-enone, we succeeded in the stereocontrolled total syntheses of dl-elemophilenolide (III) and dl-furanoelemophilane (IV). The most difficult problem encountered in carrying out the total synthesis of the compounds was a stereoselective introduction of adjacent cis-dimethyl groups to cis-decaline derivative which is a mobile molecule between steroidal and nonsteroidal conformers. Settlement of the problem was achieved by a following pathway. Dields-Alder adduct 2 was methylated to give the carbinols 12 and 13 (1: 1). The carbinol 13 was easily separated from its epimer 12 by the formation of chloromercurial 14. The intramolecular oxymercuration of 13 was influenced by the solvent and reaction time (Table 1). Under an appropriate condition, the carbinol 13 gave an oxide 16 and/or 20 selectively. The oxide 16 was converted to a mixture of ketones 25 and 10 through 18 (scheme 4). The ketone 25 was epimerized to 10 by passing through a short alumina column. Similarly, 20 was converted to cis-dimethyl-cis-decalone derivative 11 via 22. Wolf-Kishner reduction of 10 and acid treatment of the product afforded a ketone 29 which was converted to an unsaturated ester 31 by Reformatsky reaction and followed by dehydration. Oxidation of the ester 31 with (t-BuO)_2CrO_2 yielded an unsaturated ketone 32 which submitted to hydrogenation and saponification to give a ketone 34. Reaction of 34 with sodium acetate in acetic anhydride gave eremophilenolide 35 which was reduced to give furanoeremophilane 36 with NaH_2 Al(OCH_2CH_2OCH_3)_2 in quantitative yield.
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  • Sachihiko Isoe, Yoshio Hayase, Takeo Sakan
    Article type: Article
    Session ID: 32
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    We report here a brief and efficient synthetic route to methyl trisporates. Methyl β-acetoacrylate prepared from methyl levulinate by bromination followed by dehydrobromination with sodium acetate was converted to the unsaturated ester ketal (II). Condensation of II with methyl propionate in refluxing benzene in the presence of two equiv. of sodium hydride yielded β-keto ester (III). Treatment of the sodium salt of III with 1-diethylaminopentan-3-one methiodide gave the diketo ester (IV). Cyclization of (IV) to the unsaturated keto ester (V) was effected by treatment with sodium methoxide in boiling methanol. In one experiment we demonstrated that three reactions II-III, III-IV, IV-V were able to be carried out successively in the same flask. Hydrolysis of the ketal group of (V) with 60% aq. acetic acid afforded the diketo ester (I), which is the key intermediate for the synthesis of methyl trisporates. Wittig reaction of the diketo ester (I) (without protecting the ring carbonyl) with the ylide of (VII) (prepared from 5-bromo-pentan-2-one by treatment with triphenyl phosphine followed by ketalization) furnished after acidic work-up a mixture of methyl 9-cis and 9-trans trisporate B an quantitative yield. This mixture was shown by v.p.c. to comprise 75% cis and 25% trans methyl trisporate B. The pure methyl 9-cis and 9-trans trisporate B were separated by preparative t.l.c. and v.p.c. The synthetic methyl trisporates thus prepared showed identity with the reported spectroscopic data.
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  • Hitoshi Takeshita, Masahiro Hirama, Mitsuyoshi Yatagai, Sho Ito
    Article type: Article
    Session ID: 33
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    Photo-sensitized oxidation of thujopsene (I), thujopsenol (III) and gurjunene (VI) were carried out in order to examine the effect of difference in the molecular geometry and other stereochemical features upon the reaction with singlet oxygen. The result also revealed the following points: i) The preferred conformation of I and all the derivatives is I_A except C_2. ii) Dioxetane or its equivalents is responsible for the cleavage of C=C bond. iii) The cleavages of cyclopropane ring were observed in the reaction of VI. iv) Thujopsadiene (II) and mayurone (IV) were prepared in a single step which may have biogenetic significance. v) VI was converted to zierane skeleton.
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  • Y. Suzuki, S Koumura, S. Marumo
    Article type: Article
    Session ID: 34
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    The metabolic transformation of (±)-epoxyfarnesol by Helminthosporium sativum yielded three optically minus products, i.e., (-)-10, 11-dihydroxyfarnesol (2), (-)-10, 11-dihydroxyfarnesic acid (3) and (-)-9, 10-dihydroxygeranylacetone (4). Owing to the more facile consumption of (+)-epoxyfarnesol than its (-)-enantiomer, the latter could be recovered from the culture filtrate after interrupted the fermentation, although in optically incompletely state. That (-)-epoxyfarnesol has the same configuration around C-10 as (-)-dihydroxyfarnesol (2) was shown by the hydrolytic conversion of the former into the latter under the controlled condition, and, also, the S-configuration was evidenced for both compounds by means of cyclization of (-)-epoxyfarnesol into a drimane-type compound ((7) and (21)) by BF_3-etherate. S-(-)-10, 11-Dihydroxyfarnesol (2) thus obtained by the aid of fungal metabolism was chemically and stereospecifically transformed into R-(+)-epoxyfarnesol (12), [α]^<25>_D+1.8^o_1 (c, 1.91), or into S-(-)-epoxyfarnesol (16), [α]^25_D-1.8^o_3 (c, 1.70), either of which is difficult to obtain from the racemic compound by common methods of resolution. S-(-)-10, 11-Dihydroxyfarnesic acid (3) was similarly transformed into R-(+)-, [α]^<25>_D+3.7°, or into S-(-)-epoxyfarnesic acid (18), [α]^<25>_D-3.2°Both enantiomers of 2, 3-epoxysgualene, i.e. R-(+)-, (30), [α]^<26>_D+1.2°, and S-(-)-, (29), [α]^<26>_D- 1.2°, were first synthesized starting from 3. Interestingly, optically minus three products were shown to have been produced from both enantiomers of the substrate, presumably through the different hydrolytic cleavages for R- and S-epoxide ring as shown in Scheme VII.
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  • Tadashi Kurokawa, Kyozo Ogura, Shuichi Seto
    Article type: Article
    Session ID: 35
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    A cell-free enzyme of Micrococcus lysodeikticus catalyzed the formation of polyprenyl phosphates ranging in carbon chain from C-20 to C-55 with a predominance of C-40. Homogenates of rabbit liver (or kidney) and yeast catalyzed effectively the hydrolysis of these long chain prenyl phosphates, but did not act on the pyrophosphate esters. It was found that lecithin stimulated markedly the chain-elongation catalyzed by the crude enzyme and that it did not affect the synthesis of polyprenyl pyrophosphates by the purified polyprenyl pyrophosphate synthetase directly. The cis, trans configuration of these products was also discussed.
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  • Yoshimasa Machida, Shigeo Nozoe
    Article type: Article
    Session ID: 36
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    From the unsaponifiable fraction of the fermentation materials of Trichothecium roseum 6157, a trichothecin producing fungus, were isolated four sesquiterpenes, III, XIV, XVII, and XXIV, all of which are thought to be biogenetically related to trichothecin (I). Their structures were determined by spectral properties of the various derivatives and/or by chemical interrelation with known compounds. Feeding experiments of [4(R), 4-^3H-2-^<14>C] MVA and the subsequent degradation of the resulting trichothecolone showed that one of the radioactive carbon atoms (C-2 of MVA) is located at C-8 as shown in XXV, which is in disagreement with the earlier work. Tritium-labelled trichodiene (XXXIII) was prepared and fed to T. roseum 6157. The radioactive trichodiene was shown to be incorporated into the trichothecolone, giving an evidence that the hydrocarbon, trichodiene, is the intermediate in the biosynthesis of trichothecin. Possible biosynthetic route is given in the scheme.
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  • Y. Ida, S. Kubo, M. Arita, T. Komori, T. Kawasaki
    Article type: Article
    Session ID: 37
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    In addition to the three furanoid-norditerpenoids, diosbulbin-A (1), -B (2) and-C (3), reported previously, four related compounds, diosbulbin-D (C_<19>H_<20>O_6, mp 226-227°), -E (C_<19>H_<22>O_6, mp 235.5-236.5°), -F (C_<20>H_<24>O_7, mp 201-203.5°) and -G (C_<19>H_<22>O_6, mp 215-216.5°), were isolated from the root tubers of Dioscorea bulbifera L. forma spontanea Makino et Nemoto. On the basis of their chemical and spectral data and correlation of D with others they are assigned the structures 4, 5, 6 and 7, respectively.
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  • Eiichi Fujita, Masayuki Shibuya, Shigetake Nakamura, Yasumori Okada, T ...
    Article type: Article
    Session ID: 38
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    A total synthesis of enmein (1) through a main route shown in Chart 1 has been attempted. As an important key intermediate, compound 10 was chosen. In this compound, the stereochemistry is identical with that of enmein, in the asymmetric centers, C-5, C-8, C-9, C-10, and C-13. First, we converted enmein into compound 21 via several steps of reactions, as shown in Chart 2. Acyloin condensation with 20 or 21 gave 22, whose Wolff-Kishner reaction (Nagata's modification) yielded the desired compound 10. The yield of each step was satisfactory. Subsequently, we carried out the transformation of 10 into enmein. As shown in Chart 3, we succeeded in this transformation under paying attention to the stereochemistry of the asymmetric centers, C-1, C-3, and C-6. Except a few steps, the yields were good. Especially, it is noteworthy that a stereoselective cyclization of ketal carboxylic acid 11 into enmein-type compound 12 proceeded in 72% yield. The last object is synthesis of compound 10. We synthesized compound 53 from the starting material 51. Stereoselective construction of ring D and migration of the double bond to C-6: C-7 are the remaining significant problems which must be challenged.
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  • A. Tahara, Y. Ohtsuka, T. Nakata, S. Takada
    Article type: Article
    Session ID: 39
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    Since a decade ago, studies on chemical conversion of pine tree rosin to biogenetically active compounds have been carried out in our laboratory. Recently, four stereoisomers (1, 14, 15 and 16) of 1, 2, 3, 4, 5, 10-hexahydro-4β, 10α-dimethyl-fluorene-4α, 6-dicarboxylic acid were synthesized from the rosin and their structures regarded as a basic skeleton of gibberellin were elucidated. During the course of this research, it was discovered that one isomer (1_a and 1_b) alone had a remarkable sweet taste and while the others (14, 15 and 16) had no taste. This taste has some bitterness besides the sweetness and (1_b) is 1600-2000 times sweeter than sucrose. The new type of sweet compound has completely different structure from the other sweet substances. Many kinds of derivatives of the hydrofluorene (1) were synthesized and correlation between sweetness and structure were studied. In order to increase the yield of (1) from the rosin, the preparative process was simplified and shortened. A skeletal conversion to the hydrofluorene from resin acid had been completed by the rearrangement of diketone (11) to (12_a). The stereochemistry of the important intermediate (12) was reinvestigated. As the result, acetoxy anhydride (46'), Grove's key compound for elucidation of (12), should be revised to (46) and an interesting epimerization at C-6 was newly found during the acetylation (12_a→46).
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  • M. Fukuoka, S. Natori
    Article type: Article
    Session ID: 40
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    In order to correlate fernane and arborane groups of triterpenoids, the 'anthrasteroid'-type rearrangement of bauera-7, 9(11)-dienyl acetate (3b) was reexamined and the product was proved not to be (4) but to be expressed by (5). The same hydrocarbon (5) was also obtained from the dienol (3c) and from the methyl ether (3d). The structure (5) was confirmed by the derivation of (3c) to a fivemembered ketone (10) through the triene (7), which formed (5) by the acid-treatment. The same aromatisation reaction was applied for 7, 9(11)-dienes (11-14) of tirucallane, lanostane, fernane, and arborane series and the same type of hydrocarbons (15-18) were obtained in good yields. The configuration of the isopropyl group in (5, 15-18) was examined by the ORD curves. An aromatisation reaction of a novel type of (3b), bauerene (6a), arundoin (1), and cylindrin (2) by dibromodimethylhydantoin-γ-collidine was examined and the formation of styrene type compounds (24-27) was suggested.
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  • T. Shingu, T. Hibino, Y. Inubushi
    Article type: Article
    Session ID: 41
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    Simplification of the NMR spectra of triterpenes related to serratenediol using Eu(DPM)_3 as a shift reagent was examined, and we observed upfield and downfield shifts in the same molecule. This is an example of the importance of the angle dependence term in the equation of McConell and Robertson. The effectiveness of the reagent in aiding the assignment of the methyl resonances in the spectra of the triterpenes was also studied. The shift parameter of a particular methyl resonance in the spectrum of a polyacetoxyl compound will be predicted by the sum of the shift parameter related to the respective complexing sites which is experimentally obtained from the model compound, if the difference in the association probability of the reagent to the complexing site is not observed between the complexing site being present independently and that present together with an additional complexing site. That is not the case and when applied the shift parameter obtained from the model compound to the spectrum of the polyacetoxyl compound, multiplication of the shift parameter by the association coefficient is needed. Although this quantitation method is very appropriate, the close agreement between the calculated and observed shift parameter values suggests that this treatment will facilitate the assignment of the methyl signals in the spectra of the polyfunctional triterpenes.
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  • Itiro Yosioka, Kanako Imai, Yoshinobu Morii, Isao Kitagawa
    Article type: Article
    Session ID: 42
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    It has hitherto been demonstrated that the soil bacterial hydrolysis method developed in our laboratory is a useful means to clarify the genuine sapogenins. By virtue of this novel method we have so far elucidated the genuine triterpenoid sapogenins of Senega root, Panax root, Ginseng root horse-chestnut, Styrax japonica pericarps, tea seeds, and Sanguisorbae Radix, and in addition, we have been able to show the method to be effective for hydrolysis of a diterpenoid glycoside (stevioside), and a monoterpenoid glycoside (dihydroharpagide). In the present study, the soil bacterial hydrolysis method has been applied to the glycosides of the titled plant, and the result has led to the isolation of new steroidal prosapogenins (designated NE-1, XIII) possessing fully acetylated arabinoside linkage at C-11 of a new steroidal sapogenin 3-epi-metagenin (IX), which is the first instance among the steroidal glycosides.
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  • Takako Masui, Terumi Kitagami
    Article type: Article
    Session ID: 43
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    Isolation and chemical structure of new bile acids from the soft shelled turtle bile were reported in this paper. 1. The bile components were separated by column chromatography according to the method of Bergstrom et al. 2. The bile salts were constituted from 60-70% of conjugate bile acids and 30-40% of free bile acids, respectively. 3. Three kinds of free bile acids, Amydic acid, Deoxyamydic acid and Trionychic acid named by us, were isolated from the bile. 5. Infrared spectrum of Deoxyamydic acid, m.p. 195-198℃ indicated the presece of deoxycholic acid nucleus, and Deoxyamydic lactone 1 (amorphous) was derived from this acid in the same manner as that of Amydic lactone 1. On this bases, the structure of this acid would be 3α, 12α, 22(or 23) ζ-trihydroxycoprostanic acid. 6. Trionychic acid, m.p. 206℃ might have 3α, 12α-dihydroxyl groups and another hydroxyl group in the steroid nucleus also, and further a secondary hydroxyl group at C_<22> or C_<23> position of the side chain. 7. The conjugate bile acids were chiefly taurine conjugate of Amydic acid and Deoxyamydic acid.
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  • I. Murakoshi, H. Kuramoto, J. Haginiwa
    Article type: Article
    Session ID: 44
    Published: October 01, 1971
    Released on J-STAGE: August 18, 2017
    CONFERENCE PROCEEDINGS FREE ACCESS
    The plants produce a number of amino acids that may be regarded as heterocyclic β-sub. alanines. Tryptophan and histidine can be considered as member of this group, but more examples are found among the "non-protein" amino acids synthesized in a more restricted manner by plants. I, II, III, IV and V are plant products that illustrate a range of heterocyclic ring structures. The common identity of these compounds as β-sub. alanines naturally leads to the idea that similar biogenetic pathways may be responsible for their formation in plants. Our recent attempts to demonstrate the reversibility of react. 1 have proved negative: some S-methylcysteine (R=CH_3) disappeared during incubation with VI, but mimosine was not formed. The Leucaena extracts also failed to catalyze transfer of the C_3 moiety from mimosine to indole, pyrazole, uracil, NH_3 or urea: transfer reaction of this kind conceivably could yield the amino acid, try., II, III, α-β-diaminopropionic acid and albizziine, respectively. However, mimosine was produced when 3, 4-dihydroxypyridine (VI) and O-acetylserine were incubated togather with Leucaena Leucocephala extracts: serine or O-phosphoserine could not substitute for the O-acetylserine. pH-activity (7.9-8.0), time course and the effect of B6 on mimosine synthetase are shown in Fig.2, 3 and 4. Mimosine formation was determined chromatographically: paper chromat., amino acid analyzer coupled to a flow monitor system (Fig. 1). During the investigation of a role of O-acetylserine as a intermediate on serine metabolic pathway in high plants, we have demonstrated the formation of β-(pyrazolyl-N)-alanine (II) by an enzyme in watermelon (Citrullus Vulgaris) seedlings from O-acetylserine and pyrazole (Reaction 2), though these are unable to detect any activity with serine and O-phosphoserine. pH represents a fairly sharp optimum for the condensation reaction (Fig.7). When reaction mixtures were incubated at 30℃, β-(pyrazolyl-N)-alanine production was linear for about 1hr. (Fig.8). Formation of II occurred from pyrazole and serine in the presence of the treated watermelon extract if acetyl CoA were also added, but the rate of reaction was only about 2% of that observed with O-acetylserine and pyrazole. The addition of pyridoxal phosphate to reaction mixtures caused neither stimulation nor inhibition of II formation. However, when 3, 4-dihydroxypyridine was added, II formation was reduced by about 40%. Both mimosine synthetase and β-(pyrazolyl-N)-alanine synthetase in Leucaena Leucocephala and Citrullus Vulgaris seedlings did not require any co-factor such as metal ions.
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