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Article type: Cover
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Cover1-
Published: August 22, 1978
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Article type: Appendix
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App1-
Published: August 22, 1978
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Article type: Appendix
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App2-
Published: August 22, 1978
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Article type: Index
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A1-A9
Published: August 22, 1978
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Article type: Index
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A10-A20
Published: August 22, 1978
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Article type: Appendix
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App3-
Published: August 22, 1978
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Kazuhiko Orito, Gerhard Kunesch, Ernest Wenkert
Article type: Article
Session ID: 1
Published: August 22, 1978
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A general synthesis of the indoloquinolizidine nucleus of the indole alkaloids of the ajmalicinoid and yohimboid types is described. The new method concists of γ-alkylation of N-alkyl-β-acylpyridinium salts with carbon nucleophiles, acid-induced cyclization of the resultant 1,4-dihydropyridine product and further elaboration of the thus-formed indoloquinolizideine. The ajmalicinoid ring system was formed by the exposure of 1-tryptophyl-3-acetylpyridinium bromide (Ia) to sodio dimethylmalonate and then to hydrogen bromide, followed by hydrogenation of the resultant vinylogus amide (IIIa). Subsequent reduction and dehydration of the products led to the racemates of the alkaloids tetrahydroalstonine and akuammigine as well as isomers of ajmalicine. A study of the same reaction sequence (Id→IId→IIId) was undertaken emanating from methyl β-(β-pyridyl-)acrylate and turned into total syntheses of yohimbine and pseudoyohimbine.
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T. Sugimura, T. Kawachi, M. Nagao, [in Japanese], Y. Seino, T. Okamoto ...
Article type: Article
Session ID: 2
Published: August 22, 1978
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A series of amino acids was pyrolyzed and was tested their mutagenicity. Basic fractions from pyrolysates of tryptophan, glutamic acid, ornitine, and serine showed potent mutagenicities to Salmonella typhymurium TA 98. The active principles from tryptophan pyrolysate were identified as 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido-[4,3-b]indole (Trp-P-2). The active principles from glutamic acid were also identified as 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-amino-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2).
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Mikio Yamazaki, Haruhiro Fujimoto, Yukio Maebayashi, Emi Okuyama
Article type: Article
Session ID: 3
Published: August 22, 1978
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In the course of the survey investigation of toxigenic food-borne fungi, some tremorogenic strains of Aspergillus fumigatus were found growing on rice and miso. From the fungus, two tremor-genic indolic metabolites, fumitremorgin A and B were isolated, and we previously reported the chemistry of these compounds (19th this symposium at Hiroshima, 1975). Eleven tryptoquivaline-related metabolites, FTC-FTN, were subsequently isolated from the same fungus, and all of the chemical structures of these metabolites were determined. Three among them were interestingly identified with those isolated from Aspergillus clavatus by Buchi et al; those were FTC, D, and N (from A fumigatus), respectively identical to tryptoquivaline, nortryptoquivaline, and deoxynortryptoquivalone (from A clavatus). Incorporation of labeled alanine and methylalanine into FTC and FTI was clearly demonstrated. The biosynthetic inter-relation in these tryptoquivaline-related metabolites was also discussed.
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Y. Oikawa, T. Yoshioka, O. Yonemitsu
Article type: Article
Session ID: 4
Published: August 22, 1978
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DDQ is the only reagent for the selective oxidation of side chains at C-3 of indoles, while oxidation of 3-substituted and 2,3-disubstituted indoles with the other oxidants usually occurs on the pyrrole ring and at the 2-substituent, not at the 3-substituent. This selective oxidation has now been applied to a synthetic work of oxidized diketopiperazine alkaloids, neoechinulin A (NEA) and fumitremorgine B (FTB). Model compounds, diketopiperazines (7 and 8) of tryptophan with glycine and L-alanine, was heated with DDQ in THF to give the corresponding dehydro compounds, 9 (21%) and 10 (60%). The DDQ oxidation of dihydro NEA (12c and 12t) synthesized from indole via several steps was next examined. In t-BuOH, 12 was cleaved to an indole-3-aldehyde (14) through three consecutive reactions, dehydration, addition of t-BuOH, and a retro-aldol reaction. When trichloroethanol was used as a solvent to avoid this side reaction, NEA (1) was isolated in 25% yield. Among other protic and aprotic solvents, dioxane was an only useful solvent. In order to synthesize FTB (15), model experiments via two different pathways involving DDQ oxidation were successfully examined.
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T. Hino, S. Kodato, K. Takahashi, H. Yamaguchi, M. Nakagawa
Article type: Article
Session ID: 5
Published: August 22, 1978
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Dye-sensitized oxygenation of Nb-methoxycarbonyltryptamine(5) in methanol in the presence of rose bengal under ice-cooling(0-1°) gave 3a-hydroperoxypyrroloindole(6) in 40% yield. The hydroperoxide (6) was reduced with dimethylsulfide to the hydroxy derivative (7) and converted to ketoamide (8) and Nb-formylketoamine (9) along with 7 on treatment with silica gel. On the other hand, when 5 in thoroughly O_2-saturated formic acid was irradiated with a halogen lamp for 1 hr in the presence of proflavin hemisulfate, dimeric compounds (21 and 22) were obtained along with Na-formyl-3a-hydroxypyrroloindole (20) and oxidative 2,3-bond cleavage products such as 8 and 9 were not isolated. Pyrroloindole dimer(21) was obtained in 13-27% yield and can be separated into racemic and meso isomers: 21a, mp 255-256°; 21b, mp 282-284°. LiAlH_4 reduction of 21(a and b) in THF gave racemic folicanthine, mp 167.5-168.5°, in 29% yield. Reduction of 21b with LiAlH_4 in dioxane gave meso folicanthine in 60% yield. Hydrolysis of 21a by NaOH-MeOH gave deformyl derivative (23a) which was reduced with LiAlH_4 in THF to racemic chimonanthine in 29% yield from 21a. Similar treatment of 21b provided meso chimonathine. These results indicated that 21a was racemic form and 21b was meso form.
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Tozo Fujii, Hiroshi Kogen, Masashi Ohba
Article type: Article
Session ID: 6
Published: August 22, 1978
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With a view to establishing the absolute stereochemistry of the Alangium alkaloid alangimarckine, the target stereoformula III was selected for synthesis. Condensation of tricyclic amino acid (-)-IX, prepared from cincholoipon ethyl ester [(+)-VI] according to previously reported procedure, with tryptamine by the diethyl phosphorocyanidate method gave tryptamide (+)-X (92% yield), which was then cyclized (POCl_3, boiling toluene) to (+)-XI in a good yield. Catalytic hydrogenation of (+)-XI (Pt/H_2, dioxane) and chromatographic separation of products afforded base (+)-XII (25% yield) and its 1'-epimer [(-)-XIII](48% yield). The two bases were separately debenzylated (Pd-C/H_2, MeOH-AcOH) to produce the corresponding phenolic bases, (-)-III and (-)-XIV, in good yields. The absolute configuration at C-1' of (-)-III and (-)-XIV was confirmed by comparison of their IR and NMR spectra and thin-layer chromatographic mobility with those of the corresponding racemic modifications of established stereochemistry. It was also supported by comparison of their CD spectra in ethanol or 0.1 N hydrochloric acid with those of emetine (XV)-isoemetine (XVI), ochrolifuanine A-ochrolifuanine B, and certain structural analogs of tubulosine. Since the synthetic base [(-)-III] has been found to match natural alangimarckine, the above results prove that stereoformula III is a complete expression for alangimarckine.
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Ichiya Ninomiya, Okiko Yamamoto, Toshiko Kiguchi, Takeaki Naito
Article type: Article
Session ID: 7
Published: August 22, 1978
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By applying enamide photocyclization, four of the representative alkaloids of hexahydrobenzo[c]phenanthridine type, which hitherto remained unexploited, have been successfully synthesized for the first time. Synthesis of Corynoline Group of Alkaloids (1), (2), and (3). The enamide (16), prepared from the 1-tetralone, was photocyclized to give the lactam (17) which was transformed into the B/C-cis-lactam (18) by reduction with NaBH_4・BF_3. Dehydrogenation with DDQ afforded the 11,12-dehydrolactam (19) which was reduced to the amine (20). Oxidation with HCO_3H afforded (±)-12-hydroxycorynoline (2) which was then subjected to hydrogenolysis to give (±)-corynoline (1). On the other hand, HCO_3H oxidation of the lactam (19) followed by LiAlH_4 reduction yielded (±)-11-epicorynoline (3). Synthesis of Chelidonine Group of Alkaloid, (±)-Homochelidonine (4). The lactam (40), which was obtained in a similar manner as above from the corresponding enamide (39), was oxidized with Pb(OAc)_4 to afford the 11,12-ortho-quinone (46) which was then reduced to give the B/C-cis-11,12-diol (47), from which (±)-homochelidonine (4) was prepared successfully.
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Seiichi Takano, Susumi Hatakeyama, Mikoto Takahashi, Yoko Takahashi, H ...
Article type: Article
Session ID: 8
Published: August 22, 1978
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A new synthetic approach to the alkaloids related to emetine (3) and quinine(5) from norbornylene(1) is described. Norbornylene(1) was transformed into (±)-norcamphor(2) which was oxidized to the bicyclic lactone(8) by Baeyer-Villiger oxidation then alkylated with ethyl bromide and allyl bromide in a stereospecific fashion to give (9) and (29), respectively. The former lactone(9) was converted into the emetine precursor(21) and protoemetinol(4) both in dl form via the α-diketone monothioketal (13). The latter lactone(29) was converted into the homomeroquinene equivalent(37) via the α-diketone monothioketal(32) which was then transformed into dl-meroquinene aldehyde(6) via the olefin formation through the phenylselenide(41). Since norbornylene(1) has been converted into a chiral norcamphor(2), the present method would be applicable to the synthesis of the above alkaloids together with various indole alkaloids in a chiral form.
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Jun Toda, Takehiro Sano, Yoshisuke Tsuda, Yoshitaka Itatani
Article type: Article
Session ID: 9
Published: August 22, 1978
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Ungiminorine, one of the highly oxygenated Amaryllidaceae alkaloid of lycorine type, has been elucidated as (3) on analogy with the structure of narcissidine (1). We transformed lycorine (5) into ungiminorine (3) in a stereospecific manner thus accomplishing its total synthesis in formal sence. 1. Synthesis of Demethylungiminorine Short treatment of diacetyllycorine (7) with neutral permanganate in acetone-water afforded the glycol-lactam (9) in moderate yield, which gave the triacetate (11) on acetylation. The stereochemistry of the glycol function was determined by detailed analysis of their H-NMR spectra (Fig. 2) which indicated that J_<H_2-H_3> changed from 10Hz in (9) into 〜0Hz in (11). This change is available only when the glycol function has α-configuration and the conformation at ring C changed from the distorted boat in (9) into the distorted chair form in (11). Warming the triacetate (11) with SOCl_2-pyridine effected the desired dehydration to yield the Δ^<3α,4>compound (13) which on LAH reduction gave demethylungiminorine, m.p. 210° (dec.) 2. Synthesis of Ungiminorine Treatment of 1-acetyllycorine (18) with POCl_3-HCl gave the chlorohydrin acetate (19) in excellent yield, which gave hippamine on treatment with K_2CO_3-MeOH or NaOMe via lycorene-oxide (17). Permanganate oxidation of acetylhippamine (20) as above yielded the glycol-lactam (21) which on acetylation and dehydration with SOCl_2-pyridine followed by LAH reduction gave ungiminorine (3), m.p. 206-208°(dec.)
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S. Kim, Y. Bando, N. Takahashi, Z. Horii, T. Imanishi, I. Ninomiya, T. ...
Article type: Article
Session ID: 10
Published: August 22, 1978
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The total synthesis of (±)-anhydrolycodoline has been reported. The Michael reaction of the keto-ester(5) with acrolein proceeded stereospecifically to give the aldehyde(6) that was cyclized to afford the keto-ols(7), in which the methyl group has the same configuration with that of the natural base. Introduction of the nitrogen function to the bridge-head of the keto-acid(17) was achieved by the modified Curtius reaction to give the urethane(18b), which was converted to the tricyclic amino-ketone(25) in 6 steps. On the other hand, treatment of 18b with dimethylsulfonium methylide afforded stereoselectively the oxirane(28) followed by reaction with malonic ester to give the lactone(29b). The amino-lactone(30) was treated with Triton B in boiling ethanol to afford the tricyclic lactam(31). Hydroboration of the urethane(33b), prepared from 31, afforded the diol(34b) regio- and stereoselectively, which was transformed to the acrylyl amide(41) in 3 steps. Unfortunately, the intramolecular Michael-type cyclization of 41 to the lactam(42) for lycodoline did not take place for a stereoelectronic reason. Dehydration of 41 with conc. sulfuric acid afforded the anhydro-amide(45), which was cyclized smoothly in the presence of sodium ethoxide and 18-crown-6 to give the tetracyclic lactam(46). Reduction of 46 with lithium aluminum hydride followed by oxidation with Jones reagent yielded (±)-anhydrolycodoline. This work also amounts to a formal total synthesis of (±)-lycopodine.
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Y. Ichinohe, H. Sakamaki, M. Hosoda, M. Aimi, T. Takido, T. Sato, M. H ...
Article type: Article
Session ID: 11
Published: August 22, 1978
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The absolute configuration of C_1-methoxyl group on aconitines (e.g., aconitine, mesaconitine, hypaconitine, neoline and chasmanine etc,) have been confirmed by the method of X-ray analyses. It is well known that alkaloids having allylic alcohol or ether moiety are susceptible to hydrogenolysis on some catalytic hydrogenations. On the basis of the character of metal catalyst, we reexamined the catalytic conversions of aconitine into deoxyaconitine, mesaconitine into hypaconitine (deoxymesaconitine), and jesaconitine into deoxyjesaconitine via the corresponding anhydro-type compounds. We attempted to convert delphinine into chasmanine, as we were able to isolate chasmanine and neoline from the roots of Aconitum sachalinense Fr. Schmidt.
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U. Nagai, M. Kawai, M. Katsumi, Y. Kani, R. Ueki, A. Tanaka
Article type: Article
Session ID: 12
Published: August 22, 1978
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Up to the present, we have studied chiroptical properties of Dnp derivatives of normal α-amino acids and related compounds, and proposed four rules relating the absolute configuration at the NH_2 bearing asymmetric carbon to the sign of the Cotton effect near 400nm. A new rule concerning N-Dnp-N-Me-amino acids is now proposed (Fig. 1). They show antipodal CD spectra to those of Dnp cyclic α-imino acid (Fig. 2, Fig. 3). This interesting results can be explained by assuming an equilibrium between two conformers as shown in Fig. 4. It has been confirmed as expected that the former four rules can be extended to β-amino acids, too (Fig. 5). Practical application of the method to an iturinic acid has been carried out. Iturinic acids are a general name given for the long chain β-amino acids occurring in some antifungal peptidolipid (Fig. 6) produced by Bacillus subtilis. The CD spectrum of the Dnp-iturinyl-pMA (Fig. 7) indicated the absolute configuration at β to be R. Examples to demonstrate applicability of Dnp-Aromatic rule to aromatic amino acids having various aromatic nuclei are also presented (Fig. 8). Finally, scopes and limitations in applying the five rules to the determination of the absolute configuration of newly found amino acids are discussed. The Dnp method can be applied safely to ca. 60% of the known abnormal amino acids, which has been picked up from the appendix table of ref. 9). Therefore, the method seems quite useful for the purpose on the title as a whole using the five rules appropriately.
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Hiroshi Abe, Masaaki Uchiyama, Yoshimasa Tanaka
Article type: Article
Session ID: 13
Published: August 22, 1978
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Spore germination of D. discoideum is regulated by a germination inhibitor as a self-inhibitor. In the course of the studies on the inhibitor of this organism, the ethanolic extract of spores collected from twenty thousands Petri plates was separated by dialysis, chromatography on Amberlite XAD-2 resin and Sephadex LH-20 gel to Provide the inhibitor (about 15mg) named discadenine. Color reactions, UV and MS spectral analyses indicated that discadenine is 6-(3-methyl-2-butenylamino)purine substituted on α-amino acid at the 3-position of the purine ring. Based on the ^<13>C-NMR and the proton-coupled spectral analyses compared with a model compound, 3-methyl-6-(3-methyl-2-butenylamino)purine, the structure of discadenine was elucidated as 3-(3-amino-3-carboxypropyl)-6-(3-methyl-2-butenylamino)purine. Starting from 6-(3-methyl-2-butenylamino)purine, (±)-discadenine was synthesized. The synthetic discadenine was identical with the natural sample on chromatographic and spectral behavior. Besides its pronounced spore germination inhibitory activity (100% inhibition at 10^<-7>M), discadenine exhibits significant cytokinin activity (approximately one-sixth level of kinetin) in the standard tobacco pith test.
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T. Fujita, Y. Takaishi, T. Shiromoto, H. Terada
Article type: Article
Session ID: 14
Published: August 22, 1978
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Two ionophor-like active principles, hypelcin A and B were isolated from fruit bodies of Hypoclea peltata which prevents the growth of Lentinus edodes, 'Shiitake'. Hypelcins were shown to be a linear polypeptide with 19 amino acid residues containing 10 α-aminoisobutyric acid residues. The N-terminus, α-aminoisobutyric acid, of hypelcin A is blocked by an acetyl group, and the nineteenth residue, glutamine, is linked by an amide bond to leucinol. The structure (8) of hypelcin A was proposed by a comparison between hypelcin A and the products of partial hydrolysis. The difference between hypelcin A and B lies in the replacement of one of the three glutamine units of hypelcin A by a mole of glutamic acid unit in hypelcin B. Hypelcins increased the respiration rate of mitochondria in the presence of succinate as substrate and inorganic phosphate. The stimulated respiration was enhanced on addition of KCl. The effects could be related to the alamethicin-like action on mitochondrial function.
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Yuji KAMIYA, Akira SAKURAI, Saburo TAMURA, Nobutaka TAKAHASHI, Eiko TS ...
Article type: Article
Session ID: 15
Published: August 22, 1978
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In the yeast, Rhodosporidium toruloides, the mating reaction between two haploid cells designated as A and a type is controlled by pheromone-like substances secreted from each mating type cell. At the initial step of mating reaction, A type cells secrete a factor named rhodotorucine A which induces mating tube formation in the opposite a type cells. In this paper, we presented the isolation and structural elucidation of rhodotorucine A which contains a novel lipophilic amino acid, S-farnesyl cystein, at the C-terminus. The amino acid sequence of rhodotorucine A was determined by dansyl-Edman degradation and enzymatic hydrolyses. Presence of S-farnesyl cystein at the C-terminus of rhodotorucine A was disclosed by proton magnetic resonance, mass spectrometry and chemical synthesis. We proposed the following structure for rhodotorucine A. H-Tyr-Pro-Glu-Ile-Ser-Trp-Thr-Arg-Asn-Gly-Cys(S-farnesyl)-OH
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S. Harada, E. Mizuta, T. Kishi
Article type: Article
Session ID: 16
Published: August 22, 1978
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A new nucleoside antibiotic, mildiomycin, was isolated from the culture filtrate of Streptoverticillium rimofaciens B-98891 in our laboratories. It is effective on powdery mildews and has remarkably low toxicity in mammalian animals and fishes. This antibiotic has a novel structure which was determined by chemical degradations and spectral studies. Mildiomycin (1) is a water-soluble, basic substance; mp>300℃, [α]_D+100°, C_<19>H_<30>N_8O_9・H_2O. On acidic and basic hydrolyses, mildiomycin afforded 5-hydroxymethyl cytosine (5), L-serine (6) and urea. On periodate oxidation in 2N-HCl, 1 also gave optically active γ-guanidino-β-hydroxy butyric acid (8). The pyran-3-en ring moiety was elucidated on the basis of ^1H- and ^<13>C-NMR data of mildiomycin and its degradation products as well as those of blasticidin S. PtO_2 hydrogenation of 1 afforded a decytosinyl compound (9, C_<14>H_<27>N_5O_7); subsequent acidic hydrolysis yielded a deseryl lactone (12, C_<11>H_<20>N_4O_4・2HCl). A ureido compound (15, C_<11>H_<21>N_3O6) derived from the lactone was cleaved by Pb(OAc)_4 oxidation to afford CO_2 and a ketone (18, C_<10>H_<19>N_3O_4). These degradation studies and spectral analyses, especially ^<13>C-NMR study, have revealed the structure of mildiomycin (1). Absolute configuration of 1 was determined by ^1H-NMR and CD spectra to be 1'R, 4'R, 5'S and 2"S within 6 asymmetric carbons.
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S. Uyeo, T. Aoki, K. Itani, T. Tsuji, W. Nagata
Article type: Article
Session ID: 17
Published: August 22, 1978
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Selective synthesis of 2β-functionalizedmethyl penicillin α-sulfoxides 15, which could be important intermediates for conversion of penicillins to cephalosporins, was accomplished as follows. Oxidation of N-nitroso penicillins with m-chloroperbenzoic acid, followed by reductive removal of the nitroso group gave penicillin α-sulfoxides selectively. Thus, 16 was converted to 21 and 19 in the ratio of 5:1, while 23 and 25 were transformed exclusively to α-sulfoxides 24 and 27, in 66% and 50% (from 22) yield respectively. Conversion of 25 to 31 (and thus to cephalothin 2) was achieved via disulfide 29 in 43% yield (AgF) or via 29 and 30 in 20% yield. Similarly, 24 could be transformed to 33, but further conversion to 37 could not be achieved. When 24 was treated with AgClO_4 in dioxane, a ring-expanded product 35 was obtained. 35 has been known as a versatile precursor of cephalosporins. Reaction of 24 with P(OEt)_3 gave 39 in good yield, whose thiazoline ring could be opened and traped as Ag-salt 40 and both 39 and 40 were cyclized to 41. Ozonolysis of 39 gave enol 43 which was converted to 3-hydroxycephem 42.
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Y. Nii, Y. Ito, K. Okano, T. Iimori, T. Izawa, S. Kobayashi, M. Ohno
Article type: Article
Session ID: 18
Published: August 22, 1978
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There are some interesting compounds originated from nature, biologically important and containing a partial structure derived from cyanoformate. For instance, kasugamycin(1), penicillin(2), cephalosporin(3), thienamycin(4), virazole(5), orotic acid(6) and an enzyme inhibitor(7) contain such a structural moiety as shown in the figures by dotted lines. The object of the present research is to find a new methodology for the synthesis of such compounds starting from cyanoformate or its correspondents as synthon. The following results were obtained and the experimental conditions were disclosed. 1. Cyanoformates were obtained in good to excellent yields from the reaction of chloroformate and sodium cyanide in the presence of phase-transfer reagents as exemplified in equation 6 (Table 1). 2. N-Substituted carbamimidoylformic acids were obtained in excellent yields under very mild condition from the reaction of an activated form of thiooxamidate with triethyloxonium fluoroborate and various amines as shown in equation 10 (Table 2). For instance, 1 was obtained in 95% yield from 9. 3. The base part of virazole was obtained in excellent yield from the reaction of 8 with formylhydrazine followed by thermal cyclization, and the regiospecific preparation of virazole is now in progress. 4. C-C Bond formation was achieved to afford 16 in excellent yield from the reaction of ethyl cyanoformate and ethyl acetoacetate in the presence of zinc chloride and triethylamine as shown in equation 16 (Table 3).
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K. Sakai, S. Amemiya, K. Kojima
Article type: Article
Session ID: 19
Published: August 22, 1978
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In 1966 Gupta etal isolated Botryodiplodin from Botryodiplodia theobromae, which exhibits antileukemic activity. The gross structure was defined by Arsenault etal by chemical ionization mass-spectrometry. McCurry etal, Wilson etal and Mukaiyama etal reported the synthesis of dl-Botryodiplodin. However its absolute configuration has not been determined yet. In this report Methylenomycin(II) was converted into natural Botryodiplodin(I). Their absolute configuration was also determined by transforming synthesised Botryodiplodin to α-naphthyl urethane (22) of (+) 2-ethyl-3-methyl butanol(21), absolute configuration of which has already been established. In the course of this conversion reaction was found the novel isomerization reaction of α-hydroxy-α-epoxide(5,9A) into the unstable β-hydroxyketone.
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M. Nukina, T. Sassa, S. Marumo
Article type: Article
Session ID: 20
Published: August 22, 1978
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Aversion was named by Cayley (1923) to the mutual inhibition of mycelial growth by the growing colonies of different strains of the same fungal species. We investigated, as the second example of aversion, the aversion factor as well as new metabolites produced by Cochliobolus lunata, as mentioned in this report. Of the ten IFO strains of the fungus tested, only one strain (IFO 5997) produced aversion factor which inhibited the growth of other eight strains. Aversion factor, named lunatoic acid A, was isolated and its absolute stereochemistry was established as shown in 1. Lunatoic acid B, a closely related metabolite of the 5997 strain, was determined to have the antipodal stereochemistry at C -7 position, as 2. 1 inhibited the growth of other strains at 3-12ppm, and the 5997 itself at 100ppm. Interestingly, the mycelia suppressed by 1 produced chlamydospore-like cells, which were shown to be viable by germinating and growing back to the normal mycelia, when the fungus was transferred to the new medium. Thus, 1 was shown to be a new type of morphogenesis-inducing substance of fungi. New metabolites, named zeaenol and lunatinin, were isolated from the 5997 by changing the culture media, and their structures were elucidated as 8 and 14, respectively. Metabolites produced by other strains were also investigated. As the results, two new metabolites, i.e., radicinol and α-acetylorcinol, were isolated, being elucidated as 18 and 21, respectively, accompanied with known metabolites such as α-resorcylic acid, p-hydroxyphenylethylalcohol and radicinin, the absolute stereochemistry of the last one was also established in this report.
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Yoshihiro Sato, Yoriko Ajiro, Taiko Oda
Article type: Article
Session ID: 21
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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It has been recognized that the Scheme 1 represents the biosynthetic pathway of griseofulvin. In this symposium the structural studies of the transformation products of 2'-propoxy analogues (13, 12, and 11, respectively) of griseophenone B, 4-demethyldehydrogriseofulvin, and dehydrogriseofulvin which are the genuine precursors of griseofulvin (1) will be reported. The three compounds were synthesized and each compound was incubated in the suspension of the mycelium obtained from 7-day-old cultures of Penicillium urticae. The products from column chromatography were analyzed by GC-MS. The results are summarized in the Scheme 4. Incubation of (12) gave three products (10), (11), and (18). The formation of (10) and (11) were expected, but (18) was unexpected product. The structure of (18) was assumed to be the enantiomer of 2'-propoxy analogue (17) of (+)-epigriseofulvin on the basis of the GC-MS data. Incubation of (13) gave (10) and (14). Similarly, incubation of (11) afforded (10) as the sole product. Penicillium urticae is a micro-organism which produces griseofulvin as one of the metabolites. In this experiment the unnatural substances having 2'-propoxy group instead of 2'-methoxy group were used as the substrates. In the case of (12) its transformation ratio into the metabolite (10) corresponded to about one tenth of that in the tracer experiments using the natural precursor (7). This would be explained due to partly the results of the less susceptivility of the enzyme systems upon the substrate with bulky substituent at the 2'-position of the corresponding natural precursor. The formation of the metabolite (18) can be recognized as the results of the reduction mechanism from the opposite site compared with the normal biosynthetic processes.
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Sansei Nishibe, Mariko Chiba, Akiyo Sakushima, Sueo Hisada, Sakae Yama ...
Article type: Article
Session ID: 22
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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The chemical assignments were given to the absolute configurations of 2-(3,4,5-trimethoxybenzyl)-3-(3,4-methylenedioxybenzyl) butyrolactone(4), thujaplicatin trimethyl ether(10), pluviatolide (2), 2-(3,4-dimethoxybenzyl)-3-(3,4-methylenedioxybenzyl)butyrolactone(3) [2R,3R], methyltrachelogenin(20), hydroxythujaplicatin trimethyl ether(23) [2S,3S], thujastandin dimethyl ether(24), dihydroxythujaplicatin trimethyl ether(25) [2S,3R] and hydroxymatairesinol dimethyl ether(35)[2R,3R,5R], allo-hydroxymatairesinol dimethyl ether(38) [2R,3R,5S] by their conversion to known compounds, whose absolute configurations have already been established. From considerations of the configuration at C-2,3 position of butyrolactone ring on the basis of CMR and CD spectral data (Table 2 and 3) of lignans listed in Table 1, it was demonstrated that CMR is highly useful for elucidation of the relative configuration and then CD for assignment of the absolute configuration.
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H. Shimada, T. Sato, T. Kinoshita, Y. Ebizuka, T. Akiyama, H. Noguchi, ...
Article type: Article
Session ID: 23
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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Application of ^<13>C-NMR to biosynthetic studies has brought about new findings in the field of natural products such as vitamine B_<12>, polyketides, terpenoids and steroids. Especially, the use of multiple labelled precursors and the detection of ^<13>C-^<13>C coupling gave the infromation that, otherwise, could not be obtained. We will report here the results of our experiments carried out to clarify the scope and limitation of the use of ^<13>C-^<13>C coupling as well as ^<13>C-^2H coupling. The intact and stereospecific incorporation of malonate-[1,2,3-^<13>C_3] was demonstrated in cycloheximide(1) Scytalone(5) labelled by acetate-[1,2-^<13>C_2]showed the presence of two different mode of acetate arrangement as shown in 7 and 8, indicating 5 is biosynthesized via symmetrical intermediate(6). The effectiveness of acetate-[2-^<13>C,2-^2H_3] in tracing the fate of acetate hydrogen in polyketide biosynthesis was demonstrated in scytalone (5), (+)rugulosin(9) and 2-hexyl-5-propylresorcinol(12). Deuterium was not only incorporated into aromatic rings but also into methylenes of saturated alkyl chains. Double labelled acetate was also applied to biosynthesis of averufin(13) and sterigmatocystin (16), intermediates in aflatoxin biosynthesis, to clarify the chirality of ^2H labelling, as well as the mechanism of bisfuranoid ring formation.
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H. Ishii, T. Ishikawa, F. Sekiguchi
Article type: Article
Session ID: 24
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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Five new coumarins were isolated from Xanthoxylum arnottianum, Rutaceae, together with ten known ones. Rutaretin Methyl Ether (1): The absolute configuration of rutaretin methyl ether (1) was established as an S by conversion into the diol (16) which was also derived from S-marmesin (3) according to the pathway in Chart 1 and 2. This fact also unequivocally provided a certification for the proposed structure of rutaretin methyl ether (1), although the possibility of the presence of its methoxy group at C_5 position could not be excluded by the reported evidences. Arnottinin (18): The structure of arnottinin, mp 191-193°, involving a Z-configuration on the double bond, was established as the formula (18) by chemical transformation of umbelliferone into arnottinin. (Chart 3). Arnocoumarin (24) and Arnottiacoumarin (25): Arnocoumarin (coumarin I) (24), mp 180-183°, and arnottiacoumarin (coumarin II) (25), mp 140-145°, were derived from S-marmesin (3) and S-rutaretin methyl ether (1), respectively. (Chart 4). Formation of an exo-methylene derivative from a dimethylcarbinol group was performed by treatment with phenylisocyanate. The Biogenetical Situation of the Coumarins Isolated from X. arnottianum: All of the coumarins isolated from X. arnottianum could be arranged according to its oxidative step as shown in Chart 5. It should be noted here that 7-demethylsuberosin (30) would be subject to a si attack by oxygen atom followed by substitution with a phenol group at C_7 to give R-columbianetin (4), while osthenol (21) to a re attack to give S-marmesin (3), although both coumarins are cooccurred in the same plant.
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T. Nomura, T. Fukai, Y. Sawaura, S. Yamada, S. Tamura
Article type: Article
Session ID: 25
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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From the root bark of the cultivated mulberry tree (a variety of Morus alba L.), two new flavones, oxydihydromorusin, kuwanon C, and two flavanones, kuwanon D, kuwanon E, were isolated. Their structures were shown to be VII, VIII, XVIII, and XXI, respectively. For the structures of morusin (I), cyclomorusin (II), compound A (III), VII, and VIII, further evidence was obtained by synthesizing of tetrahydrokuwanon C tetramethyl ether (XVII). Photo-sensitized oxidation of I in the presence of sensitizers afforded III, VI, XXII, and XXIII. The possible mechanism of the formation of these compounds from I was discussed.
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Takuo Kosuge, Kiyoshi Sugiyama
Article type: Article
Session ID: 26
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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A number of simple alkylated pyrazines has been focused as flavor components of roasted foodstuffs. As one of Mechanistic studies on the formation of alkylpyrazine in roasted foodstuffs, a model reaction of α-ketocarbinol with α-amino acid was investigated. Reaction of acetoin and D,L-phenylalanine produced tetramethylpyrazine(TMP) in high yield. Intermediates [III],[VI],[VII] and [VIII] shown in scheme 6, were isolated from the reaction mixture, and they were converted in to TMP in high yield respectively. The other compounds such as phenylacetaldehyde, formic acid, carbondioxide, phenethylamine and ethylbenzine were also detected in the reaction. Thus a plausible mechanism of the formation of TMP was proposed as the scheme 6.
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H. Kameoka, Y. Demizu, Y. Iwase, M. Miyazawa
Article type: Article
Session ID: 27
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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From the steam volatile oils of the title plant, four novel cyclic sulfur compound were isolated to be respectively determined as 3,5-dialkyl trithiolan (3-6). The steam volatile oil was subjected to column chromatography on alumina, and cyclic sulfur compounds separated from the benzene fraction. Compound of (1), M^+180, analysed for C_6H_<12>S_3. The physical data (including i.r. n.m.r. and m.s.) suggest that is a dialkyl trithiolan with structure (1) or (2). The low-field position of the methine protone (δ ca 4.6) suggests structure (1) in which the hydrogen is adjacent to two sulfur atoms rather than (2). No optical activity was detected for compound of (3) and (4), indicating cis-isomer and trans-form. From difference of shift of each proton on the n.m.r., and an intense i.r. band at 720Cm^<-1> is evidence for the cis-form, determined (4) is cis-3,5-diethyl 1,2,4-trithiolan, (3) is trans-3,5-diethyl 1,2,4-trithiolan. Similarly, compound (5) and (6), M^+166, analysed for C_5H_<10>S_3. From physical data determined (5) is trans-3-methyl 5-ethyl 1,2,4-trithiolan, (6) is cis-3-methyl 5-ethyl 1,2,4-trithiolan.
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T. Fujiwara, K. Arai
Article type: Article
Session ID: 28
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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A new dialdose dianhydride derivative (1) consisting of two different hexoses, L-rhamnose and D-galacturonic acid, was obtained from an acid hydrolysate of the water-soluble polysaccharide of wobaku wood by successive treatment with methanolic hydrogen chloride and acetic anhydride-pyridine. It was found by methylation analysis that compound (4), the reduction product of (1), gave the alditol acetate derivatives of 3,4-di-O-methylrhamnose and 3,4,6-tri-O-methylgalactose in a molecular ratio of 1:1. NMR spectrum of (1) showed that it was the tetraacetate having dianhydride structure. Therefore, it was concluded that the structure of (1) was the 1,2':1',2-dianhydride of 3,4-di-O-acetyl-β-L-rhamnopyranose and methy 3,4-di-O-acetyl-α-D-galactopyranosyluronate. The conformations of two sugar residues in (1) were determined to be 1C(L) for rhamnose residue and C1(D) for galacturonic acid residue. (1) was synthesized from 2-O-(α-D-galactopyranosyluronic acid)-L-rhamnopyranose (5) by successive treatment with 5% methanolic hydrogen chloride and acetic anhydride-pyridine, showing that (1) is a cyclization product of (5). Formation of the dianhydride reached maximum within 4 h, in both 2.5 and 5% methanolic hydrogen chloride at 90℃.
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M. Nozaki, T. Ogawa, M. Matsui
Article type: Article
Session ID: 29
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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Stevioside, a naturally occurring sweet substance, was isolated in 1931 from Stevia rebaudiana Bertoni. Synthesis of steviol (3), the aglycon part, has already been achieved. In order to complete the total synthesis of stevioside (1), we have studied the reconstruction of the carbohydrate unit of this molecule. Since the availability of synthetic steviol as the starting material for the further transformations is limited, chemical degradation of stevioside into steviol was first studied. Thus, NaIO_4 oxidation of stevioside and subsequent treatment of the product with base afforded a high yield of steviol. The glycosidation of steviol methyl ester, readily prepared from steviol by the treatment with diazomethane, by the use of heptaacetyl sophorosylbromide gave, after saponification, α- and β-sophoroside 17 and 8 in 86% and 3.1% yields respectively. Treatment of 8 with n-PrSLi afforded steviol bioside (5). Formation of the glycosyl ester linkage in stevioside was achieved in a following manner. Steviol bioside (5) was first transformed into tributyl stannylester (7). The reaction of acetobromoglucose with 7 and subsequent deacetylation afforded stevioside and its α-anomer in 61% and 23% yields respectively. Thus, we could complete the total synthesis of stevioside in seven steps starting from steviol, which in turn had been synthesized from cyclohexanone in 26 steps. In order to achieve a stereocontrolled β-glycosidation at tertiary ca alcohol, α stepwise approach to sophoroside part is also examined.
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Haruo Ogura, Hiroshi Takahashi
Article type: Article
Session ID: 30
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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Syntheses of nucleoside analogs with glycosyl isothiocyanates (1a,b,c) are reported. Reaction between 1a,b,c and ethyl 3-aminocrotonate gave a mixture of glycosylaminoisothiazoles(6a,b,c) and glycosylthiocarbamoyl crotonates(7a,b,c), and the later compounds were readily cyclized to 6a,b,c. Similar reaction of 1a,b,c with 6-amino-1,3-dimethyluracil yielded glycosylaminoisothiazolo[3,4-d]-pyrimidines(8a,b,c). Reaction of 1a,b,c and diamines (o-phenylenediamine, 2,3-diaminopyridine, or 5,6-diamino-1,3-dimethyluracil) afforded glycosylthioureides(11a,b,c), followed by heating with methyl iodide to give glycosylamino-benzimidazoles(12a,b,c), -3-deazapurines(13a,b,c) or-theophyllines(14a,b,c) through a cyclode-sulfurization. Reaction of 1a,b,c with 2-hydrazinopyridine or 6-hydrazino-1,3-dimethyluracil gave glycosyl thiosemicarbazides(17 or 18a,b,c). Oxidative cyclization of 18a,b,c with NBS afforded glycosylaminopyrimido[4,5-e]-1,3,4-thiadiazines(20a,b,c), followed by heating to give glycosylaminopyrazolo[3,4-d]pyrimidines(21a,b,c). Reaction of 1a with hydrazinocarbonyl compounds and hydrazino compounds gave glycosyl thiosemicarbazides(22a,30a). Treatment of the former with PPA gave glycosyl-1,2,4-trizolin-3-one(28a) and that of the later with phosgene yielded glycosyl 1,3,4-thiadiazolone(33a). Methylation of 30a with methyl iodide gave glycosyl-S-methylthiosemicarbazide(31a), followed by treatment with phosgene to give glycosyl-5-thio-1,2,4-triazolin-3-one(32a). Reaction of 1a with thiourea in the presence of methyl iodide gave glycosyl isobiuret (36a), which is an useful intermediate for nucleoside analogs. Treatment of 36a with triethyl orthoformate yielded s-triazine glycoside(37a).
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Isao Kitagawa, Masayuki Yoshikawa, Akiko Kadota, Kiyoharu Shirakawa, H ...
Article type: Article
Session ID: 31
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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Recently, we have developed four selective cleavage methods for the glucuronide linkage which is contained in the oligoglycosides such as saponins. They are photolysis, lead tetraacetate degradation, acetic anhydride-pyridine degradation, and anodic oxidation. During the course of the studies on the reaction pathways and the scope and limitation of these degradation methods, we have found that aminocyclitols are conveniently synthesized from uronic acids by employing oxidative decarboxylation reactions which are brought about by lead tetraacetate treatment and anodic oxidation. via Lead Tetraacetate Degradation. Studies on methyl uronides (1, 2, 10, 12) have shown participation of "dialdehyde intermediate (i or ii)", which is readily trapped by nitromethane in the alkaline medium to furnish nitrocyclitols (14, 16, 18). By employing these reaction procedures, N-acetyl-D-glucosamine (20) has been transformed to hexaacetyl-streptamine (29) in 8% overall yield. Furthermore, starting from the glucuronide-saponin (eg. 30), the aminocyclitol oligoside (eg. 36) has been synthesized. via Anodic Oxidation. Studies on methyl glucuronide (1) have shown that the oxidative decarboxylation reaction induced by anodic oxidation can also be a favorable reaction step for the conversion of uronic acids leading to aminocyclitols. Constant current electrolysis, followed by nitromethane cyclization, reduction, and acetylation, have successfully converted D-glucuronic acid (39) to aminocyclitols (48, 50). It is noteworthy in this case that protection of the free hydroxyls in starting 39 is unnecessary. It should be mentioned here that present synthetic methods for aminocyclitols could be applicable for the conversion leading to the corresponding aminocyclitols not only from uronic acids, but also from neutral sugars and amino-uronic acids.
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Kazumichi Uotani, Masashi Miyamoto, Tadahiko Hazato, Hiroshi Naganawa, ...
Article type: Article
Session ID: 32
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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Esterastin (1, C_<28>H_<46>N_2O_6) which has been isolated from the culture of Streptomyces lavendulae No. MD4-C1 exhibits a strong inhibiton against pancreatic esterase. Methanolysis of 1 with 0.01N NaOH in methanol at room temperature afforded a δ-lactone (3, m/e 350, C_<22>H_<38>O_3), a methyl ester (7, m/e 383, (M+1)^+) and L-N^α-acetylaspartimide (8). Mild hydrolysis of 1 with 0.01N NaOH in aqueous dioxane at room temperature gave a β-lactone (10, m/e 350) and N^α-acetyl-L-asparagine. Mild hydrolysis of tetrahydroesterastin (2) afforded a tetrahydro derivative (13, m/e 355, (M+1)^+) of 10. The β-lactone in 13 was decarboxylated at 200℃ into an E-olefin (14, m/e 310) with retention of the initial geometry of the β-lactone. Periodate-permanganate oxidation of 14 gave L-3-hydroxymyristic acid and enanthic acid. Therefore, the structure of 14 was decided to be (7E,10S)-7-heneicosen-10-ol. From the results of PMR spectral analysis and periodate-permanganate oxidation, the absolute structures of 3, 7 and 10 were determined. The stereochemistries of two Z-olefins and the S-configuration at C-3 were confirmed by PMR spectra. Therefore, the absolute structure of 1 can be proposed to be (2S, 3S,5S,7Z,10Z)-5-[(S)-2-acetamido-3-carbamoylpropionyloxy]-2-hexyl-3-hydroxy-7,10-hexadecadienoic lactone. Esterastin (1) is the first mycolic acid β-lactone produced by Streptomyces.
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K. Ueda, D. Uemura, Y. Hirata, S. Takano
Article type: Article
Session ID: 33
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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The isolation and structure elucidation of palytoxin, a potent coelenterate toxin, have been studied. Though palytoxin was not obtained as a crystalline form, the structures of λ233 and λ263 chromophores in palytoxin were determined. Oxidation of toxin with NaIO_4 was suitable for elucidation of these chromophores and the positive part to ninhydrin in palytoxin. On the other hand, in the course of our studies on toxin of Palythoa tuberculosa we have isolated four compounds (3), (4), (5), and (6) characterized by their absorption maxima at 310nm, 320nm, 332nm, and 360nm, respectively. Structures of these compounds and a 334nm UV-absorbing substance (7) isolated from Porphyra species were established.
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Y. Nagao, K. Kaneko, K. Kawabata, E. Fujita
Article type: Article
Session ID: 34
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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We have exploited the reactions utilizing "Soft-Soft specific affinity" between the divalent sulfur atom and the soft acid metal salts, e.g. thallium trinitrate (TTN) and mercuric perchlorate (MPC), as well as oxidation potential of the trivalent thallium atom. Now, the general synthetic methods using these reactions for the biologically active synthons (e.g. α-diketones, diosphenols, α-oxodimethylketals, α-keto acids, α-dimethoxy-γ-butyrolactones, etc.) have been established. The outline is shown in the text as Methods A and B. These procedures were shown to be very useful for synthesis of the family of the biologically active natural products. Thus, flavonols, steroidal derivatives, parent keto acid equivalents of the essential amino acids, and the synthetic intermediates for antibiotics (avenaciolide and sarcomycin) were successfully synthesized via a rapid key reaction under mild conditions. A new finding of methyl 2-nitrophenyl disulfide (21) as a unique bissulfenating reagent is noteworthy.
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Tamotsu FUJISAWA, Kunikazu SAKAI, Takeo KOBORI, Hiroko SHIRAKATA
Article type: Article
Session ID: 35
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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The construction of the ω-side chain in prostaglandins was mostly achieved so far by the C-C bond forming reactions such as the Wittig condensation of an aldehyde with a phosphorane, or the Michael addition of an organocuprate to a cyclopentenone. We report here a new route to prostaglandins via a fulvene with a side chain of a ω-side chain equivalent. Reaction of cyclopentadiene with 3,3-ethylenedioxyoctanal (7) in the presence of an anion-exchange resin (Amberlite IRA-400) gave 6-(2,2-ethylenedioxyheptyl)fulvene (8). The Diels-Alder adduct (9) of the fulvene with α-chloroacrylonitrile gave 7-anti-(3-oxo-1-trans-octenyl)-5-chloro-5-cyanobicyclo[2.2.1]heptene (15) by the treatment with an acid, which is reported as an intermediate of 12-epiprostaglandins. On the other hand, the Diels-Alder adduct (11) of the fulvene with α-chloroacryloyl chloride was derived to 7-(3,3-ethylenedioxyoctylidene)bicyclo[2.2.1]heptenone (10). The acid catalyzed reaction of 10 gave a mixture (6:4) of 7-anti- and 7-syn-(3-oxo-1-trans-octenyl)bicyclo[2.2.1]heptenone (16 and 17). The later compound was subjected to the Baeyer-Villiger oxidation to give lactone 18, followed by the iodolactonization, acetylation and reduction to yield cyclopentanolactone 20, which is reported as an intermediate of natural prostaglandins.
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Munehiko Nara, Shun-ichi Yamada, Shiro Terashima
Article type: Article
Session ID: 36
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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Aiming to overcome several inefficient aspects of ordinary chemical resolution of racemic compound, we have developed the new methodology which recommends utilization of symmetrically functionalized meso-compound as a resolution substrate in place of racemic compound. As shown in Scheme I, when meso-compound(1) is monofunctionalized by a chiral compound and each of the formed diastereomers (2 and 3), separable by fractional recrystallization or chromatography, is submitted to further chemical elaboration including protective group transposition, it is theoretically possible to convert the total amount of the starting material into one requisite optically pure synthetic intermediate(6 or 7) by selecting synthetic operations. By employing this novel concept, the optically pure prostaglandin intermediate(Scheme II, (-)-9) has been prepared from the meso-diol(8) via the two diastereomers(10 and 11) which are produced by the reaction of 8 and N-methanesulfonyl-(S)-phenylalanyl chloride. In a similar manner, another optically pure prostaglandin intermediate(Scheme III, (-)-19) and optically pure steroid intermediate(Scheme IV, (-)-25) have been successfully synthesized from the corresponding meso-diols(18 and 24), respectively. These successful results seem to clearly disclose wide generality of the exploited novel methodology.
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Kazuo Achiwa
Article type: Article
Session ID: 37
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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The syntheses of new chiral pyrrolidinephosphine ligands (4,5,6) and their applications to the catalytic asymmetric syntheses of some chiral natural compounds were discussed. Thus, optically active α-amino acids (8) (83-91% optical yields), salsolidine (14)(45%), pantolactone (18)(86.7%), β-amino acids (23)(55%) and a-methylsuccinic acid (25)(94%) were attained in almost quantitative yields.
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Tetsuji Kametani, Hideo Nemoto, Hiroo Matsumoto, Keiichiro Fukumoto
Article type: Article
Session ID: 38
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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A new type of asymmetric total synthesis of estradiol (6) has been described. The key step is a thermolysis of optically active 1-tert-butoxy-3-ethenyl-2-[2-(4-methoxybenzocyclobutenyl)-ethyl]-2-methylcylopentane (4) to form stereoselectively 17-O-tert-butyl-3-O-methylestradiol (5), which was converted into estradiol (6) in two steps. The key intermediate 4 was in turn prepared by the condensation of 1-cyano-4-methoxybenzocyclobutene (18) with (+)-(1S,2S,3S)-1-tert-butoxy-3-ethenyl-2-(2-iodoethyl)-2-methylcyclopentane (17) followed by reductive decyanation, the latter of which was derived from the known (1S,3aS,7aS)-1-tert-butoxy-3a,4,7,7a-tetrahydro-7a-methyl-5(6H)-indanone (7) through the following four compounds, namely, (+)-(1S,3aS,7aS)-1-tert-butoxy-3a,4,7,7a-tetrahydro-[6,6-(propane-1,3-dithio)]-7a-methyl-5-indanone (9), (-)-(1S,2S,3S)-1-tert-butoxy-2-[2,2-(propane-1,3-dithio)ethyl]-2-methyl-3-[2-(2-nitrophenylselenyl)ethyl]cyclopentane (12), (-)-(1S,2S,3S)-1-tert-butoxy-2-methyl-3-[2-(2-nitrophenylselenyl)ethyl]-2-(2-hydroxyethyl)-cyclopentane (14), and (+)-(1S,2S,3S)-1-tert-butoxy-3-ethenyl-2-methyl-2-(2-hydroxyethyl)cyclopentane (15).
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J. Tsuji, T. Takahashi, K. Kasuga, T. Mandai, S. Hashiguchi, M. Takaha ...
Article type: Article
Session ID: 39
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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Several telomers obtained by the palladium catalyzed telomerization of butadiene with nucleophiles have functionalities suitable for simple synthesis of certain macrolides. A new method of lactone formation based on intramolecular alkylation of a carbanion generated by phenylthio group was used for the macrolide syntheses. The 12-membered Recifeiolide was synthesized from 9-nitro-1,6-decadiene obtained by the telomerization of butadiene and nitroethane. The telomer of butadiene and acetic acid was used for the synthesis of the 12-membered Lasiodiplodin and the 10-membered Diplodialides. Also a model compound of the 14-membered Zearalenone was synthesized.
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Gilbert Stork, Yoshiaki Nakahara, Yuko Nakahara, William J. Greenlee
Article type: Article
Session ID: 40
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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Several regiochemical and stereochemical problems are discussed, the solution of which resulted in the total synthesis of cytochalasin B and A. I. Diels-Alder reaction of triene and conversion of Δ^<6,7> to Δ^<6,12> 7-hydroxy system. II. Problems in the introductions of benzyl group and angular hydroxyl group. III. Regiochemical considerations of Diels-Alder adducts. IV. Preparation of the optically active dienophile 86. V. Preparation of the triene 111. VI. Diels-Alder reaction between the triene 111 and the dienophile 86 gave the adduct 113 possessing the desired stereochemistry as the major product. Reductive cleavage of the bromoepoxide 116 afforded Δ^<6,12>-7-hydroxy compound 117 which satisfied all the chiral centers of cytochalasin B. Extension of two carbons on the side chain and subsequent saponification completed the formal total synthesis.
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Takeshi Wakamatsu, Kozo Akasaka, Yoshio Ban
Article type: Article
Session ID: 41
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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A novel simplified method of the alkylation of alicyclic lithium 1,2-enediolates has been developed by us to create a convenient synthesis of the medium ring sizes (Scheme 1). Based on this method, the total synthesis of diplodialides A(1), C(2), and decan-9-olide (3) was achieved by the following route. 1) Decan-9-olide (3) Bicyclic glycols (8a) and (8b) readily prepared by the alkylation of 1,2-enediolate (7) with 1-iodobutan-3-ol were oxidized to give ten-membered keto lactone (9), which was converted to (±)-decan-9-olide (3) by two steps. 2) Diplodialide C (2) Decan-9-olide (3) was transformed to cis-α,β-unsaturated lactone (12), which upon epoxidation followed by epoxide opening yielded (±)-diplodialide C (2) and epidiplodialide C (14). 3) Diplodialide A (1) Oxidation of (2) and (14) afforded β-keto lactone (15), which in turn was converted to diene lactone (19a) and (19b) by four steps. Hydrolysis of (19a) with trifluoroacetic acid gave (±)-diplodialide A (1) as a sole product. A similar hydrolysis of (19b) produced a mixture of (±)-diplodialide A (1) and cis-diplodialide A (20) in a ratio of 7:5. On the other hand, hydrolysis of (19a) with hydrochloric acid afforded only cis-diplodialide A (20).
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Kojiro Wada, Tatsuyoshi Ishida
Article type: Article
Session ID: 42
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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The inhibitors of biologically active isoprenoid biosyntheses are not only useful as a tool of the study on the biosynthetic pathways, but also used as agricultural chemicals or medicines. This paper will report total synthesis of diplodialide-A which is a steroid hydroxylase inhibitor and screening study on the inhibitors of gibberellin biosynthesis. (I) Total Synthesis of Diplodialide-A The key intermediate(6) was prepared by the reaction of the dianion of ethyl acetoacetate with the bromibe(5). The seco acid(8) was transformed to the thiol ester(9) and its dilute xylene solution was refluxed under argon to give (10). The introduction of a double bond to the γ-position of the β-keto-lactone(11) has been performed by the γ-selenenylation of the dianion of (11) follewd by selenoxide elimination. Both antipodes of (±)-diplodialide-A were synthesized by GLC separation of the diastereoisomeric mixture of the acetal, (15) and (16), and the following reactions. (II) Inhibitors of Gibberellin Biosynthesis Resuspended mycelium of G. fujikuroi was used for tests. In our screening study of the inhibitors of gibberellin biosynthesis, 1-geranylimidazole and 1-decylimidazole showed inhibition of GA_3 biosynthesis at 12.5ppm(66% inhibition) and 6.25ppm(74% inhibition), respectively. These compounds inhibited C-19 oxygenation of (-)-kaurene and kauren-19-ol, but not the transformation of kaurenoic acid to gibberellin.
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T. Kitahara, M. Matsui, K. Mori
Article type: Article
Session ID: 43
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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Macrolide antibiotic, (+)-brefeldin A(1) was isolated from fungi (P. cyaneum, P. brefeldianum etc.) and it shows some bacteriocidal and strong phytotoxic activities. Though the synthesis of dl-compound was achieved by Corey et al from cyclopentadiene and the intermediate was prepared by Crabbe et al via different route, optically active (1) is not synthesized yet. We, select the cyclopentanonitrile derivative (24), having all three correct stereochemistry in it's molecule, as the key intermediate. Starting from D-mannitol, lactone-acid (28) was prepared via several steps and cyanomethyl group was introduced into C_2-position, accompanied with decarboxylation. Major isomer (65% of product) was converted to the precursor (38) for intramolecular cyclization in 5 steps and base treatment gave the desired intermdiate (24), stereochemistry of which was confirmed by comparing CD spectrum and [α]_D of cyclopentanone derivatives, obtained from (24) in 6 steps, with reported value. Vinyl group was transformed to acetylenic group and then alkylation gave the product containing necessary side chain at C_5-position. Further studies for the synthesis of (1) is now in progress.
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J. Inanaga, T. Katsuki, S. Takimoto, S. Ouchida, K. Inoue, A. Nakano, ...
Article type: Article
Session ID: 44
Published: August 22, 1978
Released on J-STAGE: August 18, 2017
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Methynolide (1), the aglycone of a macrolide antibiotic, methymycin (2), was synthesized via its 8,9-didehydro derivative (27), as described below. The acetylenic intermediate (13) was synthesized starting from the optically active dihydroxy acid (3) through the acetonide aldehyde (5). The Prelog's lactone (18) was obtained starting from meso-2,4-dimethylglutaric anhydride (14) in six steps including the separation procedures, in 11.6% overall yield. The methyl ester (19) of the resolved 18 was transformed into the acid bromide (21) in which the hydroxy group was protected by chloroacetyl group. Condensation of 21 and the silver salt of 13 led to 22 which was then converted into the seco-acid (24) by successive reduction, deprotection, reprotection, and hydrolysis. For the lactonization of 24, a newly developed procedure in which the mixed anhydride of a hydroxy acid and 2,4,6-trichlorobenzoic acid was treated with dimethylaminopyridine in refluxing benzene, was used. This procedure had been proved to be effective for the large ring lactonization of an acid-sensitive hydroxy acid such as 7. The acetylenic lactone (25) thus obtained was then deprotected, oxidized, and reduced to give 1, which showed the same properties as reported for the specimen derived from natural methymycin (2).
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