The oxygenation of 3-hydroxyflavones in DMF in the presence of ButOK resulted in the formation of the corresponding depsides and carbon monoxide in nearly quantitative yield through oxidative cleavage of the heterocyclic ring of 3-hydroxyflavones. The oxidative cleavage of 3-hydroxyflavones was also caused by oxygenation catalyzed with cobalt or copper complexes in DMF. The present results can provide a nonenzymic model for the reaction of quercetinase. The catalytic oxygenation was highly affected by solvent and substitution at 4'-position with OH group, which accelerates the reaction. 3',4'-Dihydroxy groups of quercetin led to the formation of complex mixture in the reaction. A plansible mechanism of the catalytic oxygenation of 3-hydroxyflavones involving radical process will be discussed.

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Finding toxicity in a methanolic extract of Leucothoe Keiskei Miq. (Ericaceae) led to the isolation of the principles, designated as poriolide (1) and isoporiolide (2). The structural elucidation and the synthesis of the aglycone of the two toxic substances, having a novel structure of the macrocyclic biphenyl-type flavanoid glycoside, will be discussed. The structure of poriolide (1) was determined by the spectral data, degradation works, and finally the X-ray crystallographic analysis of a bromide (25). The structure of isoporiolide (2), an isomer of poriolide, was derived from a comparison of the degradation products of poriolide, isoporiolide and their derivatives. On hydrolysis with barium hydroxide, both poriolide and isoporiolide gave the identical propiophenone glycoside (11a), but isoporiolide yielded an isomer (27a) of the carboxylic acid (12a) obtained from poriolide. The structure of the carboxylic acids (12a and 27a) was confirmed by an unambiguous synthesis. A key point of the synthesis of the aglyconeis the construction of the unsymmetric biphenyl compounds, this point was effected by application of the rearrangement reaction of suitable phenyltropone derivatives to biphenyl compounds.

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From the leaf juice of Aloe species (Aloe arborescens Mill. var. natalensis Berger), which has been widely used for a medicinal plant, we isolated a new bitter glucoside, named aloenin, together with aloe-emodin, barbaroin, magnesium lactate, succinic acid, sitosterol, n-triacontanol, n-dotriacontanol, D-glucose, potassium chloride, and sodium chloride. The presence of aloe-emodin and barbaroin has been known already, but the other components have not been reported yet in Aloe species. We now present evidences leading to structure 3 for the new bitter glucoside, aloenin. This is an unique example of naturally occurring chromene having the carbomethoxyethylidene group on C-2. The incorporation experiment of sodium malonate-2-^<14>C and phenylalanine-3-^<14>C in the Aloe plant suggested that aloenin (3) is biosynthesized by the cyclization of the polyketide as formula 14, which is formed through the acetate-malonate pathway.

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The yellow pigments named eumitrins A_1, A_2, and B were islelated from the lichen, Usnea bayleyi (Stirt.)Zahlbr. The modified bixanthone structures of these compounds were deduced mainly from their spectral data, and their absolute structures (XII, XIV, XV) were established on the basis of X-ray crystallographic analysis of a transformed product(XVIII) of tribromoeumitrin B (XVI).

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Blast caused by Pyricularia oryzae is the most destructive disease of the rice plant in Japan and the metabolites of this fungus have been expected to be responsible for the symptoms of this disease. The ethylacetate extract of the culture broth filtrate of P. oryzae was separated by chromatographies. Pyriculol I which causes a dark-necrotic spot on a rice leaf, and related compound II, IIIa and IIIb were isolated. The structural determinations of these compounds were based on the spectral data, chemical transformations as well as their microbial interconversions. Compounds IV, V and VI were isolated and were found to reduce or stimulate the growth of rice seedlings. The structure of IV was determined by preparing from 2-hydroxyjuglone, and the structure of V and VI were elucidated by comparisons of their spectral data with that of IV. The known compound Tenuazonic acid VII and a diketopiperazine VIII were also isolated as the metabolites of this fungus, theirphytotoxic activities and antifungal activities were studied. An attempt to synthesize pyriculol I and related compounds is in progress.

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In the course of the studies on enzyme inhibitors produced by micro-organisms in our laboratories, oudenone was discovered in a culture filtrate of Oudemansiella radicata in 1970, and it showed inhibition of tyrosine hydroxylase and exhibited significant hypotensive effect. Oudenone is structurally unique, existing as 2-[4,5-dihydro-5-propyl-2(3H)-furylidene]-1,3-cyclopentanedione (1) and 2-(4-hydroxyheptanoyl)-1,3-cyclopentanedione (2b) in solid state or acidic medium and basic solution, respectively. Oudenone has been synthesized by the reaction of 2-acetyl-1,3-cyclopentanedione and furfural followed by hydrogenation over Pt in the presence of 1 mol equiv. of sodium hydroxide and neutralization. 2-[3-(2-Tetrahydrofuryl)propionyl]-1,3-cyclopentanedione (8) has been transformed to 1 by treatment with HI followed by hydrogenation. Oudenone homologues 12, 13, 14, 15, 16, 17, 18, 19, 20 have been synthesized by various methods and their inhibitory activity to tyrosine hydroxylase was investigated. It has been shown that the most important part for the biological activity is attributed to β-trione moiety.

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From the fermentation broth of Streptomyces venezuelae MCRL 0376 separated macrolide antibiotics, pikromycin (amaro-mycin), narbomycin, pikronolide, and narbonolide. NMR and CD studies of these macrolides and their aglycones suggested the conformation of macrolactones. Carbonyl group at C_9-position of pikromycin, acetyl pikromycin, and pikronolide showed a cisoid relationship between double bond at C_<10>-position. On the other hand, transoid relationship between the double bond and the carbonyl group was considered for narbomycin, narbonolide, diacetyl pikromycin, and kromycin (aglycone I of amaromycin). Stereochemistry of carbonyl group at C_3-position of pikromycin should be have two type A and B in the different solvent.

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The methanolic extract of air-dried young leaves of bracken (Pteridium aquilinum Kuhn var. latiusculum Underwood (Pteridaceae) (Japanese name, warabi) was fractionated as shown in Chart 1 and seventeen kinds of sesquiterpenoids having 1-indanone nucleus (1-17) were isolated. Physical properties of these compounds, designated pterosins, are shown in Table 1 and Table 2. The substitution pattern in pterosin B (1), the major constituent, was confirmed by the degradation (1→19→20) and the other reactions shown in Charts 2 and 3. The ozonolysis of 1 afforded (+)-methylsucccinic acid, indicating (R)-configuration at 2-position in 1. The structures of the congeners (2-17) including the stereochemistry were suggested by the spectral data and confirmed by the correlations shown in Charts 2 and 3.

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Ozonolysis of α-dihydrosantonin B (3) and santonin α-oxide (1) gave δ-lactol type compounds (4) and (11), respectively. (4) gave δ-lactol methyl ether (6) on treatment with diazomethan while it produced an aldehyde ester (9) with methyl iodide. On the contrary, the aldehyde ester (13) was obtained on treatment of (11) with diazomethane or methyliodide. (15) derived from (4) under acid or alkali conditions afforded a new lactone (17) due to the cyclohexane ring inversion and the lactone ring reclosure in (15). (4) and (11) transformed on treatment with to benzimidazoline derivatives (30) and (32), respectively, as well as with ethylenediamine to the imidazolidines of (34) and (36), respectively.

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Biogenetic type reactions of preisocalamendiol (I) and its derivatives (II-V) were carried out under acidic as well as basic conditions. In all cases, stereospecific cyclizations take place to give cadinane-type, selinane-type or guaiane-type compounds depending on reagents, solvents and so on.

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Three new furanoeremophilanes were isolated from Farfugium japonicum Kitam., and their structures were determined as 6, 7 and 8. Two new furanoeremophilanes isolated from Farfugium hiberniflorum were shown to be represented by 9 and 10. Conformations of 6, 7, 11 and 15 are discussed. Furanoeremophilane-6β,10β-diol (1) was treated with POCl_3 in pyridine to give 4, 5 and 20. Absolute configurations of 1 and 4 were determined as 1a and 4a, respectively; this shows a retention of configuration at C-9 of 4a, excluding the route (D→G→4b). Cyclohexadienyl cation D (delocalized) initially formed rearranges into 4a via E and F. Formation of 5 and 20 from D can also be interpreted as shown in H.

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The key intermediates (2, 2a, 23) in the syntheses of eremophilane sesquiterpenes were prepared by the indirect Robinson annelation method. (1) The reaction of isocamphorquinone (1) and trans-pent-3-en-2-one in the presence of sodium alcoholate gave complex products. Five neutral and two acidic products were separated. (see Table) The neutral products were stereoisomeric 2-hydroxy-7-isopropylidene-2,4,5-trimethylbicyclo[3.3.1]nona-6,9-diones (5, 6, 7) and the Michael adducts (3, 4). And also the acidic products were 2-hydroxy-7-isopropylidene-6-oxo-2,4,5-trimethylcyclooctanoic acid (8) and its dehydrated derivative (9). The structure of these products were determined by means of chemical and spectroscopic investigations. The three bicyclo[3.3.1]nonane derivatives were transformed to octalone derivatives (2, 2a) by acid catalyzer. 2 and 2a were converted to compound 12, 15, and 17, respectively. (2) The condensation reaction of 2,3-dimethylcyclohexane-1,4-dione (19) and MVK in the presence of sodium ethylate was carried out. Theree crystalline products (20, 21, 22) were separated by column chromatography. Treatment of 20 with TsOH in benzene afforded a expected product enone (23; 80% yield) and together with a small amount of nonane derivatives (22, 24). Chemical conversion studies of some eremophilane type sesquiterpenes from the above key intermediates are in progress.

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In a course of our studies on chemical constituents from Hepaticae, three new sesqueterpenoids were isolated together with cuparene from the liverwort, Bazzania pompeana (Lac.) Hitt. These compounda were named bazzanene ε-cuparenol and bazzanenol and their structures were respectively determined as 2,6,6-trimethyl-8-methylene bicyclo[5.3.1]undec-2-ene (II), 2-methyl-5-(1,2,2-trimethylcyclopentanyl)phenol (III) and 2,6,6(-trimethyl-8-methylene bicyclo[5.3.1] undec-2-en-4-ol (IV) by chemical and spectrometrical methods.

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α-Longipinene (1) is a sesquiterpene isolated from the essential oil of Pinus silvestris or Swedish sulfate turpentine, and the skeletone involves a pinane moiety. In this study the unique skeleton was constructed by intramolecular photocyclo-addition of cyclodecadiene derivatives as the key step. Trimethylcyclodecadienone (9) was synthesized from acetoxy-octalone (13) as shown in the text. Contrary to expectation, irradiation of (9) afforded only a Norish fission product (25) as the sole isolable product. On the other hand, triene (10) derived from (9) gave the desired photocyclized product (12) on sensitized photolysis. Norketone (11) was obtained from the latter and submitted to Tiffneau-Demyanov rearrangement giving ketone (31). Treatment of (31) with methyllithium followed by dehydration gave α-(1) and β-longipinenes (33).

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The syntheses of α-cis-bergamotene and jasmone derivatives were studied by utilizing new reactions developed by the use of organo sulfur compounds. I. Lithium salt of dimethylally 2-pyridylsulfide was treated with 9-iodo-α-pinene(6) to yield α-alkylated product(7), which was reduced with CuCl_2-LiAlH_4 to afford α-cis-bergamotene(5). IIa). 2-Methylcyclopentanone was easily converted to 5,5-bis(phenylthio) derivative(11) by the reaction with sulfenamide. Then 11 was alkylated with triallylborane and hydrolysis and dehydration of 12 with AgClO_4 afforded allyl-rethrone(9). b). Di[bis(phenylthio)alkylmethyl] copper lithium was react with conjugated enones and 1,4 addition products(14) were exclusively obtained. The products(14) was converted quantitatively into 1,4-diketone(15) by hydrolysis with CuCl_2-CuO. By this method dihydrojasmone(16) was obtained from heptanal diphenylthioacetal in only 3 steps.

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Synthetic approaches to the insect juvenile hormones (JH, I and II) ard their analogs are discussed in detail with a brief summary of structure-activity relationship and possible use of JH for silkworm rearing. Stereoselective synthesis of the cis-double bond portion of JH. Three new routes were developed for this purpose: (i) Mevalonolactone (IV) was converted to a C_6-alcohol (VIII). (ii) A C_7-alcohol (XVII) was prepared from methyl cyclopropyl ketone (XII). (iii) Methyl vinyl ketone (XX) was converted to VIII. Synthesis of dl-C_<17>-Cecropia JH. This was accomplished non-stereoselectively (XIX→XXVIII). Stereoselective synthesis of 6-ethyl-10-methyldodeca-5-trans, 9-cis-dien-2-one (XXIX). The stereoselective ring fission of XXXIII to XXXIV enabled us to prepare XXIX stereoselectively (IX→XXIX). This was further transformed into dl-C_<18>-Cecropia JH. in the usual manner. Stereoselective synthesis of dl-C_<17>-Cecropia JH. Coupling and subsequent modification of the two structural units, XLIII and XLIV, afforded dl-C_<17>-JH. XLIII was prepared stereoselectively from geraniol. Conversion of farnesol into the 10-trans-isomer of dl-C_<17>-JH. A stereoselective homologetion of the trans-terminal methyl group of farnesol (XLVIII) to an ethyl group yielded the 10-trans-C_<17>-JH (LIV). Structure-activity relationship. Two alkyls at C-11 are essential for high JH activity. An alkyl at C-7 was less important. An alkyl at C-3 was unnecessary. Practical use of JH. JH application on the silkworm, Bombyx mori, remarkably increased the yield of silk.

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4-Methyl-Δ^3-dihydrothiapyran or its synthetic equivalent was utilized as a structural unit of Cecropia juvenile hormone. After appropriate synthetic operations, the blocking sulfur atoms were removed by reductive desulfurization. By these methods, the sterea pecific syntheses of C_<18>-J.H., C_<17>-J.H., and two homologues of J.H. have been achieveu.

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It is known that the structural requirement for the allylic pyrophosphates (2 and 3) to condense with isopentenyl pyrophosphate (1a) by the action of farnesyl pyrophosphate synthetase is not very stringent with respect to the alkyl groups R_1 and R_2 in 2, but that certain homologs of type 3 and 4 where R_3 is CH_3 can be synthesized enzymatically from proper artificial substrates. As to isopentenyl pyrophosphate homologs, only 3-ethyl-3-butenyl pyrophosphate (1c) acts as a substrate for the enzyme in place of isopentenyl pyrophosphate (1a) to give new farnesyl pyrophosphate homologs, the stereochemical course of the condensation of 1c being exclusively trans. trans, trans, cis-3,11-Dimethyl-7-ethyltrideca-2,6,10-trien-1-ol (bishomofarnesol) and its pyrophosphate, possible precursors for the biosynthesis of insect juvenile hormone were synthesized enzymatically from cis-3-methyl-2-pentenyl pyrophosphate (18), 1c and 1a.

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Structures of diverpenoids grayanotoxin XV, leucothol A and B have been determined respectively as 2, 5 and 7 by X-ray crystallographic analyses. Grayanovoxin XIV and leucothol C have been characterized as 1 and monoanhydroleucothol B (8) respectively by chemical means. Grayanotoxin I, II and III have been degraded to a tricyclic compound 19 by the route outlined in Scheme 1. Partial synthesis of grayanotoxin II from 19 has been achieved through the sequence of reactions given in Scheme 2.

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In the 15th Symposium of The Chemistry of Natural products which was held in 1971 at Nagoya, we reported the chemical conversion of enmein (1) into diol (2) and also a partial synthesis of enmein from (2). Now, we succeeded in the synthesis of racemate (36) and the chemical conversion of its optically active enantiomer (41) into (2). Thus, a total synthesis of enmein was accomplished. 5-Methoxy-2-tetralone was converted into (5), from which the desirable compounds (10) and (11) were derived through several steps of reactions shown in Chart 2. The structures of these compounds were chemically confirmed as shown in Chart 3. The Birch reduction with (10) proceeded exceedingly efficiently, and the desired ketone (23) was obtained in good yield. Some considerations about the intramolecular participations of hydroxy groups were tried. The stereoselective construction of ring D was achieved by the route shown in Chart 6. The product (36) was identified with its optically active enantiomer (41) which was derived via (39) and (40) from enmein. Compound (41) was converted into (2) by tetrahydropyranylation and dehydration followed by ethylene-acetalization as shown in Chart 7.

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Two new triterpenoid glycosides, ovalifolioside and lyofolic acid were isolated from the leaves of Lyonia ovalifolia DRUDE var. elliptica HAND.-MAZZ. Ovalifolioside(I) gave ovalifoliogenin(II) and L-arabinose by acidic hydrolysis. Monoisopropylidene derivative of II was oxidized to monoketone and reduced by Wolff-Kishner method to yield the compound V, which was correlated with hederagenin(VI). Tritylation and oxidation of ovalifoliogenin yielded a 1,3-diketone(VII) and α,β-unsaturated ketone(VIII). The position of the arabinoside was confirmed as 3 by NMR data of oxidation product of monoisopropylidene derivative of I, which contains one aldehyde and keto group. Lyofolic acid IX contains one acetoxyl group, one carboxylic group and one isolated methylene group of cyclopropane. Acidic hydrolysia of IX gave lyofoligenic acid(XI) and glucose. XI contains no cyclopropane but a tetrasubstituted ethylene group. Trisnordiol(XVII), derived from lyofoligenic acid, was correlated with lanosterol(XVI) and suggested that the structure of genic acid should be XI. Protolyofoligenic acid(XVIII) was isolated from the extract of the leaves. XVIII has been derived to trisnordiol carboxylic acid(XIX), which was converted to the same trisnordiol acid XIII with methanolic hydrogen chloride. Lyofolic acid consumed 3 moles of sodium periodate. Thus, glucose must be attached to 3-position of the genin and the acetyl group must be attached to 6-position of the glucose.

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We have found that the culture filtrate of a fungus, Cladosporium sp., induced chlorosis of higher plants, and isolated five active principles. One of them was identified as cephalosporin P_1(I), and others were new compounds, viri dominic acid A, B, C and isoviridominic acid A (VA-A, B, C and IsoVA-A). From chemical and spectral data, these compounds were shown to be analogues of (I). Ozonolysis of VA-C triketone(XI), which produced and ene-dione(XII), showed that VA-C has the structure (IV). By the chemical correlation to (IV), the structures of VA-A and IsoVA-A were assigned to (II) and (V), respectively. The structure of VA-B was assigned as (III) by CrO_3 oxidation of methyl ester (XV) and dehydration of dihydro-ol triacetate(XXI). The biological activities of these compounds indicated that the configuration of C-11 functional groups and their presence or not were important to their activities.

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1) Ternstroemiaxanthin A new carotenoid, ternstroemiaxanthin, was isolated from the red seeds of "Ternstroemia japonica" (mokkoku) as a main constituent, and the structure of the pigment was determined by spectral and chemical methods to be 3-hydroxy-β-ψ-caroten-18'-al (I). This is the first example of the presence of aldehydic C_<40>-carotenoid in higher plants. 2) Two Acetylenic Aromatic Carotenoids Among seven carotenoid hydrocarbons isolated from a sea sponge "Reniera japonica", two minor pigments, m.p. 205℃ and m.p. 194℃ have been remained structurally unsolved because of the paucity of materials. Recently considerable amount of samples has been isolated and enough evidences have been obtained to conclude that they have structures of acetylenic aromatic carotenoids (VII) (m.p. 205℃) and (IX) (m.p. 194℃) respectively. This is the first establishment of the natural occurrence of acetylenic aromatic carotenoids. In order to confirm these structures, synthesis of these pigments have been carried out. The Wittig condensation of phosphonium salts, XIII and XXVI, with C_<25>-aldehyde (XVI) gave 3,4-cis-products which were identified with the stereomutation product of natural products.

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The circular dichroism analysis based on the exciton theoretical treatment has been carried out on several natural products having simple chromophore systems, such as dihydrotampaulipin A acetate, dihydrocostunolide, gibberelleic acid, neophorbol triacetate, dihydro-yuzurimin-B-mesylate and π-endo-dicyclopentadiene. The results gave additional support to the author's proposal that the current method of determining absolute configuration of the X-ray crystal analysis should be revised so as to give the antipodal configuration. Other interesting molecules showing conspicuous CD spectra will be presented.

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We report a new highly stereospecific total synthesis of PGF_<1α> (1), which proceeds in good to excellent yield at each step. Four asymmetric centers on the cyclopentane ring required for the synthesis of PGF_<1α> was introduced stereospecifically by the catalytic reduction of the enone (6) with palladium on charcoal (6→7: the formation of three asymmetric centers), followec by sodium borohydride reduction (7→8: the formation of additional one asymmetric center).

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The main urinary metabolites of prostaglandins F_<2α> (1) and E_2 (2) were recently isolated and identified as 5α,7α-dihydroxy-11-ketotetranorprosta-1,16-dioic acid (3) and/or its δ-lactone (4), and 7α-hydroxy-5,11-diketotetranorprosta-1,16-dioic acid (5) respectively. Interest on biological activities of prostaglandin metabolites promoted us their synthesis. The γ-lactone (6), which was already stereospecifically synthesized, was chosen as a starting intermediate and transformed to six menbered lactone (7) by five steps: diisobutylaluminium-hydride reduction, Wittig reaction in order to introduce one more carbon atom, acid-catalized hydrolysis, and silver oxide oxidation followed by acetylation. The δ-lactone (7) thus obtained was converted to the α,β-unsaturated keto-lactone (20) by three steps: boron tribromide de-methylation, chromium trioxide pyridine complex oxidation, and condensation with dimethyl 2-keto-6-carbomethoxy-hexylphosphonate (19). Catalytic hydrogenation of the enone (20) afforded the keto-lactone (21) which was hydrolized to give the prostaglandin F_<2α> metabolite (4). The identity of the metabolite (4) was confirmed by comparison of mass spectrum of the methoxime derived from keto-lactone(21).

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The structures of five new polyoxypregnane derivatives: caudatin, ikemagenin, isoikemagenin, Gagaminin and Glycocynanchogenin which had been isolated from the aglycone fraction of Cynanchum caudatum Max. (Asclepiadaceae) besides four other known substances: lineolon isolineolon, deacylmetaplexigenin and sarcostin, were discussed. On the bases of chemical and physico-chemical evidences, above new compounds have been concluded to have the structures Ia, IIa, IIb, IIIa and IVa respectively. We have measured the ^<13>C nmr spectra of a series of C/D cis polyoxypregnanes and have been able to make satisfactory assignments of nearly all of the resonances by auxiliary techniques such as noise-modulated total proton decupling, off resonance proton decoupling, hydroxyl acylation effects on chemical shifts, solvent effects and substituent influences in analogous compounds. The ^<13>C nmr were for more informative than proton nmr for structural analysis of this series.

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Previously we have found that fucosterol-24,28-epoxide(V) was converted into desmosterol(IV) by a brief treatment with BF_3-etherate. The similar reaction was postulated to occur in the dealkylation step of β-sitosterol(II) in the phytophagous insects. To clarify this hypothesis, [2,4-^3H]_fucosterol-24,28-epoxide(V), fucosterol(III), isofucosterol(IX) and 24-methylene-cholesterol(VIII) were ingested in the larvae of the silkworm, Bombyx mori, and found to be transformed in cholesterol(I) in the yields of 15,10,1.9, and 3.2%, respectively. When a large amount of the epoxide(V) was feeded, followed by ingestion of ^3H-fucosterol(III), 2.4% of the ^3H-activity was trapped in V, while the incorporation in cholesterol(I) decreased to 1.6%. These data suggests that V is a possible metabolic intermediate between III and I. In conjunction with the previous findings, we propose II→III→V→IV→I (scheme 5), as one of the main dealkylation routes in insects. The other candidate, e.g. II→IX→VIII→IV→I, postulated as the reverse way of phytosterol biosynthesis (scheme 6) seems to be, if any, a by-path, from the small incorporation of IX and VIII. The nutrition studies showed I, II, III, IV, V, VIII, and IX satisfied the sterol requirement of B. mori, while the insects feeded with VI, VII, XI, XII or XIII were died during the first instar. The latter observations would exclude the third route(scheme 9), reminiscent of the side chain cleavage of cholesterol(I) in vertebrates.

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Early chemical studies of bufotoxin type toad venom constituents culminated in the bufotalin 14-suberoylarginine structure for bufotoxin (vulgarobufotoxin) in 1941. Structural evidence has been accumulating that both bufotoxin (5)and marinobufotoxin (23), which was recently isolated from the Brazilian toad Bufo icerticus Spix by Linde-Temple, are in fact the each 3-suberoylarginine esters of bufotalin (1) and marinobufagin (18). We now wish to report the portial synthesis of bufotoxin (vulgaro-bufotoxin) (5) from bufotalin (1) and also synthesis of marino-bufotoxin (23) from marinobufagin (18). This particular interconversion unequivocally supports the 3-suberoylarginine proposal for the so-called bufotoxin structure. In an analogous series of experimentals, bufalin (6) was converted into bufalin 3-suberoylarginate (bufalitoxin; 7), and also resibufogenin (8) was converted into resibufogenin 3-suberoylarginate (resibufotoxin; 9). The preceding experimental should provide a useful model for synthesis of related toad poison toxins. In addition, we wish to report conversion of the 14β-hydroxy-bufadienolides, telocinobufagin (10), bufotalin (24), and gamabufotalin (37) into the 14β,15β-epoxy-bufadienolides, marinobufagin (18), cinobufagin (30), and 11α-hydroxy-resibufogenin (45), respectively, employing the 14-dehydro compounds (12, 25, and 40) as relay, as shown in scheme 4, 5, and 6.

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From Bruguiera conjugata (Rhigophoraceae) two new substances, named Brugierol and Isobrugierol, have been isolated for which the structures I and II (trans- and cis-4-hydroxy-1,2-dithiolane-1-oxide) are proposed respectively on the basis of spectroscopic evidences and the synthesis.

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Structure From the extracts of etiolated young asparagus (Asparagus officinalis L.), we isolated three compounds, named asparagusic acid (I), dihydroasparagusic acid (III), and S-acetyldihydroasparagusic acid (V) respectively. The structure of I, III, and V was determined by physical evidence including the use of shift reagent in NMR and was confirmed by synthesis as shown in the scheme. Physiological properties Asparagusic acids (I, III, V) inhibited the growth of the seedlings of lettuce, rice, and other plants when applied in amount of 6.67×10^<-7> M to 6.67×10^<-4> M. The extent of activity was similar to that of abscisic acid (Fig. 1 and 2). Interaction with benzyladenine, gibberellin, and indoleacetic acid In the enlargement of radish cotyledon and lettuce hypocotyl growth, the inhibitory effects of I were completely overcome by benzyladenine and GA_3 respectively (Fig 3 and 4), while I showed the inhibitory effect on the growth in the presence of IAA (Fig 5). Stimulation of Streptococcus faecalis 10 C 1 Asparagusic acid stimulated growth and respiration of Streptococcus faecalis 10 C 1. The result was shown in Table 1 and Fig. 6.

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The preparation of α-D-glucopyranoside in high yield still remains one of the most important problems in carbohydrate chemistry. Although several methods have been reported the yields are not so high. The mechanism of and the solvent effects in the Koenigs-Knorr reaction of glycosyl halides having non-participating group at C_2 position using silver perchlorate as catalyst were studied. It is considered that the reactions substantially proceed via a common intermediate, the glycosyl perchlorate. By the application of this result, β-isomaltose octaacetate was obtained in 75% yield from 3,4,6-tri-O-acetyl-2-O-benzyl-β-D-glucopyranosyl chloride with one molar equivalent of 1,2,3,4-tetra-O-acetyl-β-D-glucopyranose using silver perchlorate and sym-collidine in ether, followed by debenzylation and acetylation. Similarly, β-maltose octaacetate, β-nigerose octaacetate, and α-kojibiose octaacetate were obtained in 43.6, 57, and 47% yields, respectively. We are indebted to Dr. B. Lindberg for kind gift of seed crystals of β-isomaltose octaacetate.

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The selective antagonists of blasticidin S elaborated by Streptomyces griseo-chromogenes var. detoxicus containing up to twenty congeners are classified into eight groups designated detoxins A to H. Detoxins show several interesting biological activities counteracting to the toxicity of blasticidin S against plant and animal cells. The separation of detoxin complex into eight groups was achieved by bufferized ion exchange resinchromatography (Dowex 50W X2, 0.2 M pyridine-acetate buffer at pH 5.0), and detoxin D group, which could be further separated into detoxins D_1, D_2 and D_3, was one of the most active component. Detoxin D_1, C_<28>H_<41>N_3O_8, mp. 156-158℃, [α]^<25>_D-16°(c 1, in methanol) is an amphoteric compound with pKa 4.0 and 8.0 and shows positive ninhydrin reaction. Acid hydrolysis of detoxin D_1 afforded (+)-2-methylbutyric acid, L-valine, L-phenylalanine and an unknown amino acid designated detoxinine. The N-terminus was determined to the amino group of L-valine by DNP and diazotization methods. Partial alkaline hydrolysis of detoxin D_1 gave valyl-detoxinine C_<12>H_<22>N_2O_5 and valyl-detoxininolactone C_<12>H_<20>N_2O_4 which were characterized as the corresponding acetates. NMR spectra together with spin decoupling experiments of the acetates of these key compounds provided the evidences on the structure of unknown amino acid detoxinine and lead to the elucidation of total structure of detoxin D_1. Application of Klyne's lactone sector rule to valyldetoxininolactone deutero-acetate gave the proof of absolute structure of detoxin D_1. The structural relationship between detoxin D_1, D_2 and D_3 was clarified and some arguements concerning the structure of detoxin C group will be presented.

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A colorless needle crystalline, mp 187-188°(decomp.), C_5H_7O_5N_3 was isolated from Quisqualis Fructus (seeds of Quisqualis indica, and Q. indica var. villosa, Combretaceae), a popular ascaricidal crude drug in China and Japan. The compound was considered to be an unknown acidic amino acid and an active principle. So it was named quisqualic acid after the genus name Quisqualis. The chemical structure of quisqualic acid was consedered to be N^2-L-alanyl-3,5-dioxo-1,2,4-oxadiazolidine(Ia) or N^4-L-alanyl-3,5-dioxo-1,2,4-oxadiazolidine (Ib) on the basis of chemical and spectral data. Therefore Ia and Ib were synthesized by routes shown in the chart 2 and 3, respectively. Ib did not agree with quisqualic acid but Ia was identified with the authentic sample. Thus, the structure of quisqualic acid was confirmed to be N^2-L-alanyl-3,5-dioxo-1,2,4-oxadiazolidine satisfactorily. Quisqualic acid is the first instance of natural compound containing 1,2,4-oxadiazolidine ring.

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Some α-amino acids(I)(L-tryptophan and L-Dopa) were subjected to the Pictet-Spengler reaction with aldehydes(II) according to the biosynthetic route. From the resultant condensation products (III) was eliminated the C_1-unit derived from the α-amino acids to give optically active compounds(IV). Using this biogenetically patterned 1,3-transfer of asymmetry, S(-)-tetrahydroharman(XVIIb) and S(-)-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine(XX) were synthesized from L-tryptophan. S(+)-Laudanosine(XXVIa) was also prepared from L-Dopa. The key steps of the 1,3-transfer of asymmetry are the Pictet-Spengler reaction, α-aminonitrile formation, followed by the reductive decyanization with sodium borohydride. Results of model reactions for the reductive decyanization are shown in the Table.

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Rhynchophylline(I) and isorhynchophylline(II) are alkaloids of Uncaria rhyn-chophylla MIQ., the structures of which were established as I and II, respectively. Although the partial synthesis of rhynchophylline from dihydro-corynantheine and synthesis of (±)-rhynchophyllol and (±)-isorhynchophyllol were reported, the total synthesis of these alkaloids has not yet been described. We now report the stereoselective total synthesis of (±)-rhynchophylline and (±)-isorhynchophylline. A condensation of 2-hydroxytryptamine hydrochloride(IV) with morroniside(III), one of secoiridoid glucosides proved to be a precursor of indole alkaloids, was attempted to afford VI and the conversion of VI into oxindole alkaloids was tried, but this project has not yet been realized. Subsequently, ethyl sodium formyl acetate(XI) was used instead of hemiacetals like morroniside and tetrahydropyranol to condense with IV, namely, a mixture of XI and IV in the 1:1.8 molar ratio, was kept at 45-48°for two days to give exclusively XIII as an oil. The compound(XIII) was condensed with ethyl α-formyl butyrate to yield the enamine(XIV), which was submitted to hydrogenation with Adams' catalyst in acetic acid, yielding the diester(XV) as two isomers. The diester(XV) was refluxed with sodium hydride in toluene and the resulting ketoester was heated in hydrochloric acid at reflux to give the ketone(XVIa, b) in two isomeric forms. The ester(XVII) was obtained as a sole product from either isomer of XVI through the Wittig condensation with methyl diethyl-phosphonoacetate. The further conversion of XVII provided stereoselectively (±)-isorhynchophylline via XIXb and XX. The synthetic sample was identified with the natural alkaloid in respects of spectral and chromatographic properties. The synthetic (±)-isorhynchophylline was converted into (±)-rhynchophylline, which was also identified with the natural rhynchophylline by i.r.(CHCl_3) and mass spectra and the Rf values of t.l.c. The compound(XIII) should be also available as an important intermediate for the synthesis of other oxindole alkaloids including uncarine and mitraphylline, which is under investigation.

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1) From the cyanogen bromide reaction of yohimbine (I), 3R-ethoxy-3,4-secocyanamide (II) had been obtained by Albright and Goldmann, but we found that a ratio of reaction products (R and S) is dependent on the molar ratio of ethanol to the substrate as shown in Table 1. Stereospecific ring closing reaction of compounds (IIIa and b) with hot acetic acid was observed to yield yohimbine (IVa=I) and pseudoyohimbine (IVb) respectively. 2) A similar result was obtained for hirsutine (V), which gave 3R and S-ethoxy-3,4-secocyanamide (VIa and b). Both compounds were stereospecifically ring closed to dihydrocorynantheine (VIIa) and hirsutine (VIIb=V) respectively. 3) Treatment of gardnerine (X) with BrCN resulted in the formation of cyanamide ether (XI) in a similar manner as voachalotine (VIII). In the ring closing reaction with hot acetic acid, compound (XI) gave rise to a new iminoindolenine derivative (XII), which was converted to Nb-methyl-3,4-secogardnerine (XVI) by 3 steps. 4) When phenylchloroformate was used instead of BrCN, in a two phase reaction with aqueous alkali and ethanol-free pure chloroform, ring opened compound (XXIV) having a hydroxy group at C-3 position was obtained in 60-70% yield from Na-methyl-gardnerine acetate (XXIII). The urethane derivative (XXIV), an amorphous epimeric mixture at C-3 position, has been reduced to Nb-methyl compound (XXII) and then desired 2-acyl type indole alkaloid (XXV), mp 199°, was obtained by oxidation with Py.-CrO_3.

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The synthetic studies on Dendrobium alkaloids have been carried out by the route considering the biogenesis that the picrotoxane skeletone is derived from cadinane (A). The synthesis of dendrobine (1), the principal alkaloid of Dendrobium nobile L. was completed. Starting from α-tetralone (2), the two diastereoisomers (10a) and (10b) of the properly functionalized cis-hydrindane were prepared. The keto acid (10a) was converted to the keto lactam (22) via intermediates (20) and (21). The isopropyl group was introduced in this stage by the sequence; (22)→(23)→(24)→(25)→(26). The epimerization of (26) followed by reduction of the keto group to the hydroxyl afforded (±)-oxodendrobine (28), which was then led to (±)-dendrobine (1) by reduction of the pyrrolidone part to the corresponding amine. As a crucial step for the synthesis of 2-hydroxydendrobine (29) and dendroxine (30), hydroxylation at C-2 of the tricyclic compound (22') was examined affording the desired product (31) in moderate yield.

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Total synthesis of dl-dendrobine has now been completed. The ketol (17) was derived to the tosylate (18) which was treated with KCN in anhydr. DMSO to give the keto-nitrile (19). Hydrogenation of (19) over 5% Pd-SrCO_3 catalyst afforded the compound (21) in high yield. Treatment of (21) with one equivalent of Br_2, followed by dehydrobromination provided the enone (19) and (34) in a 3-4: 1 ratio. The compound (19) is circulated as the starting material for the compound (34) by hydrogenation of (19) to the compound (21). The compound (35) obtained by ketalization of (34) was refluxed in KOH-ethyleneglycol-H_2O (2:4:1) to give the keto-lactone (5). The compound (5) or (46) was heated with aq. CH_3NH_2 in the presence of CH_3NH_2・HCl to provide the lactam (6). The lactam (6) was successively treated with isopropyl-MgBr, KHSO_4 (dehydration), I_2-AgOAc-AcOH-H_2O, aq. MeOH-KOH, and CrO_3-pyridine to give the enone (7) and (49) in 10 and 20% yield, respectively. Hydrocyanation of (7) with Et_2AlCN gave the cyano-ketones (50), (51), and (8) in 18, 20, and 29% yield, respectively. Reduction of (50) with NaBH_4, followed by hydrolysis with aq. KOH and acidification with dil. HCl provided dl-oxodendrobine (53) and its isomer (52) in 25 and 50%, respectively. dl-Oxodendrobine (53) was also synthesized from the compound (8) through the hydroxy-nitrile (54), imino-lactone (55), and tosylate (56). Another route to dl-oxodendrobine from the compound (8) through the compound (57) and (58) was also carried out. Reduction of dl-oxodendrobine by the method of Borch gave dl-dendrobine.

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The D,E-ring system of dl-camptothecin (+ Camptothecin is an alkaloid with a novel ring system exhibiting potent antileukemic and antitumor activity) was synthesized by application of Vilsmeier reaction to a model compound III, followed by addition of malonester (Chart I). This D,E-ring formation was not successful with XV, but the tetrahydro derivative XVIII could undergo the ring formation to give lactone XXI, which was converted to dl-camptothecin. The 4-methoxy-2-pyridone ring moiety of XV was obtained by a unique intramolecular aldol-type condensation (Chart II).

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Woodward-Hoffmann rule would provide the effective method for the synthesis of the complicated or strained compounds. Therefore, we investigated the synthesis of the isoquinoline alkaloids along this rule. Thermolysis of 1-benzocyclobutenyl-3,4-dihydroisoquinolines gave the protoberberines. which were reduced to afford the berbines, xylopinine and discretine. On the other hand, photolysis of the phenolic bromoisoquinoline gave (-)-O-methylandrocymbine and (-)-kreysigine. Moreover, cepharamine, a hasubanan alkaloid, was synthesized by a photolysis of the diphenolic bromoisoquinoline, followed by treatment with methanolic hydrochloric acid.

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Acetoneberberine type enamine (2) gave 8,13a-propanoberbine derivatives on the following three reactions; a) oxidation of (2) with potassium permanganate, b) annelation via (2) as intermediate on the treatment of protoberberine type alkaloids with acetone in the presence of alkali, and c) alkylation of (2) with alkyl halide. The structures of 8,13a-propanoberbine derivatives were deduced from chemical and spectral data. Acidic hydrolysis of 8,13a-propanoberbine derivatives, Hofmann degradation product (24), and possible mechanism for this intramolecular cyclization of acetonyl group of (2) are discussed. The analysis of mass spectra of 8,13a-propanoberbine derivatives leading to find a characteristic fragmentation pattern is also discussed.

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Some tentative structures [(3)-(8)] have been proposed for the O_5-benzo[c]-phenanthridine alkaloids isolated from Papaverous plants on the basis of their NMR spectra. However, other structures could not be rigidly excluded from consideration, because the NMR data on nitidine type alkaloids did not coincide with the result of the analysis which was used to structural establishment of the above O_5-alkaloids. The direct comparison of those alkaloids to the synthetic specimen may be most powerful tool to the confirmation of the structures of them. Therefore, Robinson's synthetic pathway of the benzo[c]phenanthridine alkaloids was examined on a model compound (9). In the course of the study, the pure cis and trans tetralin formamides (16a and b) and the corresponded amino derivatives (17a and b) were obtained. These experiments disclosed that reduction of the tetralone oxime (19) with Na-Hg gave a cis amino compound (17b) as a rather main product, while such a reaction is well-known to give a thermodynamically controled product, a trans-isomer. And also the cis-and trans-derivatives of tetrahydro-(22a and b) and hexahydrobenzo[c]phenanthridine (23a and b) were prepared. Furthermore, it was found that Bischler-Napieralski cyclization of the formamide (38) which has no methoxy group at the para position could not proceed.

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Aconite root(Bushi in Japanese) has been used for a long time as one of the most important ingredient of chinese medicine as heart stimulant, diuretic agent and anodyne. Previous works on aconite root have been mostly focused on alkaloids such as aconitine, ignavine, kobusine and so on. And this paper deals with isolation and structure determination of a cardiac principle of aconite root. Isolation of the principle has been succeeded by a limited combination of gel-filtration through Sephadex LH-20 and counter current distribution to give pale yellow powder which stimulates flog's heart even on one hundred millionth dilution. The powder was designated as yokonoside. Yokonoside is β-glucoside and is very soluble in water and slightly soluble in alcohol. By methylation of yokonoside, followed by acid hydrolysis Me-yokonol, trimethyl derivative of the aglycon, was obtained as crystalline needle. Me-yokonol has following properties, mp. 146°(from EtOH) colorless needle C_<17>H_<17>NO_6, soluble in CHCl_3, Me_2CO, slightly soluble in EtOH, benzene, uv: λ^<EtOH>_<max> mμ(logε), 220(4.55), 240s (4.20), 283(3.95), 347(4.08), ir: (KBr) cm^<-1>, 3250, 2800,1680 1645, 1600, 1540, 1495, 1435, 1310, 1280, 1220, 1060, 1040, 820 780, mass: m/e(%), 331(80), 299(40), 284(30), 181(100), 166(60), 151(60), 150(40), 149(80), nmr: in CDCl_3, δ, 11.95(s,1H) 11.77(s,1H), 8.65(d,j=9.0,1H), 7.53(d,j=3.0,1H), 7.25-6.90(multiplet,4H), 3.95(s,3H), 3.85(s,3H), 3.82(s,3H). The structure of Me-yokonol was determined as (XI) by a comparison with synthetic sample, thus the structure of yokonoside was elucidated as (XV).

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