The synthesis and antiviral activity of racemic carbocyclic 2', 3'-dideoxy-3'-fluoro nucleosides are reported. Carbocyclic 2', 3'-dideoxy-3'-fluoro nucleosides were obtained from the 3-fluoro cyclopentane derivative 4, which was prepared by two methods. The SN2-displacement of the hydroxyl group of (±)-(1β, 2α, 3β, 4β)-4-acetamido-2-fluoro-3-hydroxycyclopentylmethyl acetate (1) with Ph₃P-I₂ followed by tin hydride reduction afforded the 3-fluoroamino alcohol derivative 3. Alternatively, the protected fluoroamino alcohol 3 was prepared by regio- and stereoselective bromo-fluorination of cis-4β-acetamidocyclopent-2-enemethyl acetate (5) with hydrogen fluoridepyridine/N-bromosuccinimide followed by tin hydride reduction to remove the bromine atom. Carbocyclic 2', 3'-dideoxy-3'-fluoroguanosine (14) thus obtained was moderately active against herpes simplex virus in vitro.

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Upon irradiation, phthalimide-indole in bichromophoric systems underwent intramolecularly remote Paterno-Buchi reaction to give oxeto[2, 3-b]indole derivatives containing macrocycles, in competition with Norrish type II reaction.

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Oxidation of 8-oxoerythrinan and 8-oxo-1, 7-cycloerythrinan derivatives with 2 mol eq of ceric ammonium nitrate in alcohols or acetic acid gave the corresponding 11β-alkoxy or acetoxy compounds in moderate yield. Thus, (±)-3, 3, 15, 16-tetramethoxy-1, 7-cycloerythrinan-2, 8-dione and (+)-erysotramidine gave the corresoponding 11β-methoxy and 11β-acetoxy derivatives on oxidation in methanol and in acetic acid, respectively. Those compounds were respectively converted into (±)-erythristemine and (+)-erythrartine in several steps, thus achieving the total synthesis of these alkaloids.

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Oxalylation of the enamino-ester 13 derived from the L-dopa derivative 12 gave the dioxopyrroline of (6S)-configuration (15A) diastereoselectively (50-60% diastereomer excess). This was converted to a mixture of erythrinans of (5S, 6R, 7R, 10S) and (5R, 6S, 7S, 10S) configuration by cyclization with BF₃·Et₂O. The de of the major diastereomer (A) was elevated to 82% by application of a kinetic resolution of diastereomers (partial hydrolysis of the ethylene acetal group), where the minor diastereomer (B) was hydrolyzed more rapidly. The acetal 17A which remained unchanged was converted, in several steps, to the enantio-type erythrinan alkaloid, (-)-3-demethoxyerythratidinone (-)-7, and also to the 1, 7-cycloerythrinan (-)-9, a key intermediate to Erythrina alkaloids. The more easily hydrolyzable diastereomer (B) was similarly converted to the enantiomer (+)-9. The mechanism of partial racemization, sometimes observed in the product, is discussed.

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3H-Pyrazolo[1, 5-a]indole derivatives were propared for the first time starting from 3-oxo-2-phenyl-3H-pyrazolo[1, 5-a]indole, which was obtained by the 2, 3-dichloro-4, 5-dicyano-p-benzoquinone (DDQ) oxidation of 3-hydroxy-2-phenyl-3a, 4-dihydro-3H-pyrazolo[1, 5-a]indole. Their reactions were briefly investigated.

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An alternative method to prepare 3-oxo-2-phenyl-3H-pyrazolo[1, 5-a]indoles starting from indoline-2-carboxylic acid was explored. The reaction with nucleophilic agents allowed us to introduce the properly substituted alkyl substituents at C-4 of the 4H-pyrazolo[1, 5-a]indoles. The 2, 3-dichloro-5, 6-dicyano-p-benzoquinone (DDQ) oxidation of these products gave the 3-oxo-2-phenyl-3H-pyrazolo[1, 5-a]indole derivatives. Selective Keto-enol tautomerizations of these 1, 5-diketo-monoene system were observed.

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Four new triterpenoids, hopan-29.17α-olide (1), hopan-17α, 29-epoxide (2), 3α-hydroxyfilic-4(23)-ene (3), and 2-oxofilic-3-ene (4), were isolated from the dried leaflets of Cyathea spinulosa, together with hop-22(29)-ene (5), fern-7-ene (6), fern-9(11)-ene (7), filic-3-ene (8), hydroxyhopane (9), dryocrassol (10), tetrahymanol (11) and cyclolaudenyl palmitate (12). The structures of the new compounds were elucidated on the bases of spectral data and chemical correlations.

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Reaction of silylketenes 1a, b with stabilized ylides 2a-e readily gave silylallenes 3a-f in high yields. However, similar reaction of 1a with the less stable ylides 2f, g resulted in low yields of the allenes 3 g, h. Use of silylketenes 5a, c with an additional trimethylsilyl group overcame this problem to give silylallenes 3c, g-k directly in considerable to good yields. In this reaction, the additional trimethylsilyl group apparently worked as a masking group.

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As typical electrophilic substitution reactions of the 4H-pyrazolo[1, 5-a]indole derivatives, the Vilsmeier-Haack-Arnold (V.H.A.) and bromination reactions were investigated in detail and mechanisms involving the 1H-pyrazolo[1, 5-a]indoles as reaction intermediates are proposed. The V.H.A. reaction products were subjected to oxidative and reductive reactions, and a novel reduction of the conjugated system involving a double bond in the aromatic (pyrazole) ring was observed. Reaction pathways for these reactions are also proposed.

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A new hydrolyzable tannin dimer [hirtellin G (1)], a trimer [hirtellin T₁ (5)] and a tetramer [hirtellin Q₁ (6)] have been isolated from the 70% acetone extract of the leaves of Reaumuria hirtella JAUB. et SP. (Tamaricaceae). These tannins were characterized as oligomers composed of two, three or four molecules of tellimagrandin II which are similarly linked with each other through one, two or three dehydrodigalloyl (m-GOG) units. Their structures including the orientations of the m-GOG units have been elucidated based on chemical degradation and spectroscopic analyses.

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Two novel ellagitannin trimers, hirtellins T₂ (1) and T₃ (25), besides previously reported hirtellin T₁ (28), have been isolated from the leaves of Reaumuria hirtella JAUB. et SP. (Tamaricaceae). Hirtellin T₂ has a 36-membered macro-ring structure (1) with three dehydrodigalloyl (m-GOG) units connecting monomers, while hirtellin T₃ (25) possesses one m-GOG and one hellinoyl (m-GO-m-GOG) unit forming a rigid macro-ring, as found in hirtellin B. Two new tannins, tamarixinins T₁ (26) and T₂ (T_2a+T_2b) (27), having a m-GOG and/or isodehydrodigalloyl (p-GOG) unit were also isolated from the flowers of Tamarix pakistanica QUAISER. The structures these new ellagitannin trimers were elucidated based on chemical methods and spectroscopic analyses, including two-dimensional nuclear magnetic resonance measurements.

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Cytotoxic sesterterpenes, manoalide 25-acetals (1a, 1b), seco-manoalide (2), (E)-neomanoalide (3), (Z)-neomanoalide (4), and heteronemin (6), were isolated from the marine sponge Hyrtios erecta (collected at Amami Island, Kagoshima Prefecture, Japan) by bioassay-guided separation and the absolute configrations of these manoalide family members have been determined. Manoalide 25-acetals (1a, 1b) were shown to exhibit in vivo antitumor activity and to inhibit the DNA-relaxing activity of mouse DNA topoisomerase I and the DNA-unknotting activity of calf thymus DNA topoisomerase II.

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A new method for the synthesis of 4-alkoxy- and 4-[alkyl (or aryl)thio]indoles has been developed by using the indolone 3 as a common intermediate. The indolone 3 was prepared from N-(phenylsulfonyl)pyrrole (7) and the α-chlorosulfide 8 in four steps. Heating of a mixture of 3 and an appropriate alcohol in the presence of p-toluenesulfonic acid and cupric chloride afforded the 4-alkoxyindoles 11a-d. The method was applied to the synthesis of (±)-pindolol (19) and (S)-(-)-pindolol (20). Thiols also reacted with 3 in the presence of boron trifluoride to give 4-[aryl (or alkyl)thio]indoles 12, 21a, b, and 22a-d. The (indol-4-ylthio)acetate 22c was employed as a key intermediate for a concise total synthesis of (±)-chuangxinmycin (27).

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Astechrome (1), isolated from Aspergillus terreus IFO 6123 and 8835, was synthesized. Indolylmagnesium bromide (4) was coupled with a chloromethylpyrazine (5) to give 2-chloro-5-methoxy-3-methyl-6-[7-(3-methyl-2-butenyl)indol-3-yl]methylpyrazine 1-oxide (6), which was converted to the Fe salt (9) of a hydroxamic acid derivative (8). Oxidation of 9 with Co(salen) afforded 1.

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The structures of two new bis-indole alkaloids, 19'(R)-hydroxyconodurine (11) and 19'(R)-hydroxyconoduramine (12), from the leaves of Tabernaemontana subglobosa MERR. (Apocynaceae), native to Taiwan, were determined by means of spectroscopic analysis and chemical reactions.

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A new convenient route for asymmetric synthesis of the epoxy fragment of azinomycin B by Sharpless asymmetric epoxidation of secondary allylic alcohol is described.

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A novel alkaloid incartine (1), a supposed biosynthetic intermediate from galanthine (2) to narcissidine (3), was isolated from flowers of Lycoris incarnata (Amaryllidaceae) together with the known alkaloids galanthine (2), ungiminorine (4), ungiminorine N-oxide (5), galanthamide (6), galanthamine N-oxide (7), lycoramine (8), sanguinine (9), lycorine (10), and O-demethyllycoramine (11). 1-Palmitoyl-2-linoleoylphosphatidylethanolamine (12) and 1-palmitoyl-2-linoleoyphosphatidylmethanol sodium salt (13) were also identified in the flower.

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Two coronand-type 18-membered lactone epoxides, i.e., geranyl dimeric lactone diepoxide (GL₂E₂, 10) and tetraepoxide (GL₂E₄, 11), were synthesized from geraniol as diastereomeric mixtures. Among them, GL₂E₄ (11) was shown to exhibit ion-transport activity for Ca²⁺ ion in the test using a W-07 (liquid-membrane type) apparatus and ion-permeation activities for Ca²⁺ and K⁺ ions across the human erythrocyte membrane. Isolation of six component diastereomers of GL₂E₄ (11) [GL₂E₄-1 (11c), -2 (11d), -3 (11e), -4 (11f), -5 (11g), -6 (11h)], was effected by HPLC separation of two diastereomeric tetraepoxides (11a, 11b) which were prepared from two diepoxides (GL₂E₂-1, 10a and GL₂E₂-2, 10b). The relative stereostructures of these diastereomers were determined by a combination of X-ray diffraction and ¹H-NMR analyses. Among the six diastereomers, S₂-symmetrical GL₂E₄-4 (11f) exhibited the strongest ion-transport activity for Ca²⁺ ion while C₂-symmetrical GL₂E₄-6 (11h) exhibited the strongest ion-permeation activity for Ca²⁺ ion across the human erythrocyte membrane.

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As a preliminary study for the synthesis of aromadendrane- and alloaromadendrane-type compounds, trans and cis B/C-ring compounds (18 and 22) were synthesized from (+)-(1S, 2R, 4R, 7R)-3, 3, 7-trimethyltricyclo[6.3.0.0^{2, 4}]undec-8-en-10-one (3) as a common intermediate, which was obtained from (+)-3-carene via an intramolecular aldol condensation as a crucial step.

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The design, synthesis and structure-activity relationships of transition-state inhibitors containing the dihydroxyethylene isostere at the scissile site are described. The compounds with (2S, 3R, 4S)-4-amino-5-cyclohexyl-1-morpholino-2, 3-pentanediol at the P₁-P_1' site are potent renin inhibitors. (2S, 3R, 4S)-4-[N-[(2S)-3-Ethylsulfonyl-2-(1-naphthylmethyl)propionyl]-L-norleucyl]amino-5-cyclohexyl-1-morpholino-2, 3-pentanediol (2) (BW-175), which is the most potent inhibitor (IC₅₀ : 3.3 nM against human renin) in this series, poorly inhibits cathepsin D (IC₅₀ : 26000 nM) and pepsin (IC₅₀ : >100000 nM), and thus it is specific for renin. Compound 2 contains only one amino acid and showed an oral bioavailability of 2.8% at 10 mg/kg and 9.7% at 30 mg/kg in rats. The interaction between renin and inhibitor 2 is discussed on the basis of molecular modeling studies.

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Three new triterpenoid saponins, their methyl esters designated as castaralesides F (1), G (2) and H (3), were isolated from the fresh leaves of Castanospermum australe. The structures of these three saponins were elucidated on the basis of chemical and spectral data as 3β-O-[β-galactopyranosyl-(1→4)-β-glucuronopyranosyl]-2β, 23-dihydroxyolean-12-en-28-oic acid; 3β-O-[α-rhamnopyranosyl-(1→4)-β-galactopyranosyl-(1→2)-β-glucuronopyranosyl]-2β, 28-dihydroxyolean-12-ene; and 3β-O-[α-rhamnopyranosyl-(1→4)-β-xylopyranosyl-(1→2)-β-glucuronopyranosyl]-2β, 28-dihydroxyolean-12-ene.

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Five new ergostane-related compounds, nicaphysalins A (1), B (2), C (3), D (4) and E (5), were isolated from the fresh whole plants of Nicandra physaloides (Solanaceae). Their structures were established by spectroscopic means. Nicaphysalins D (4) and E (5) had a folmyloxy group at C-22 in the side chain.

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Five novel steroidal glycosides 2-6 were isolated from the whole plant of Asclepias fruticosa L. (Asclepiadaceae). The structures of these steroidal glycosides were determined on the basis of spectral and chemical evidence. All of these glycosides contain 2, 6-dideoxyhexopyranoses as component sugars and their structures were elucidated as polyoxypregnane-type glycosides, which have linecolon as the aglycone moiety.

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Phytochemical studies of the bulbs of Scilla peruviana, Eucomis bicolor, Chionodoxa gigantea and C. luciliae gave respectively two new and two known, four new and two known, three known, and one new and five known lanosterol oligosaccharides. The structures of the new compounds were determined from spectroscopic data. A total of 19 lanosterols, including previously isolated compounds, were examined for inhibitory activity on 12-O-tetradecanoylphorbol 13-acetate (TPA)-stimulated ³²P incorporation into phospholipids of HeLa cells as the primary screening test to find new antitumor-promoter compounds.

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The dissolution of oval soft gelatin capsules containing 5 mg of nifedipine dissolved in a water soluble vehicle was evaluated by the rotating dialysis cell (RDC) method and the paddle (PD) method as described in the Japanese Pharmacopoeia (JP) XI. The dissolution pattern of nifedipine obtained by the PD method was linear, and almost 100% of the content was dissolved within 7 to 10 min. The dissolution pattern obtained by the RDC method corresponded to the absorption pattern vs. time curve obtained by the oral administration test in humans. When the RDC method was performed with the cell containing a buffered solution coupled with n-octanol as the dissolution medium, the in vitro dissolution pattern best simulated the in vivo absorption pattern.

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Solid dispersions were prepared with a highly water soluble medicine (oxprenolol hydrochloride (OXP)), water insoluble ethylcellulose (EC) and water soluble hydroxypropyl cellulose (HPC). The release profiles of OXP from the solid dispersion granules at various composition ratios of the components, and the suppression mechanism of the release rate in the OXP-EC-HPC system, were studied.The release rate of OXP reached a minimum level at the HPC composition ratio of 5-10%. It was difficult to control the release rate with more than 10% HPC. It was found that a marked decrease in the release rate at the HPC composition ratio of 5-10% was caused by the formation and retention of the swelled phase of HPC in the EC matrix. At more than 10% HPC, because OXP molecules enclosed by HPC molecules or incorporated in the swelled HPC phase increased and most of the OXP molecules were released together with HPC by erosion, the release rate of OXP increased drastically in the early stages of the release process. At the OXP composition ratio of 30% or more, the diameter and volume of the pores formed by the OXP release markedly increased, since the aggregates of OXP molecules that showed crystallinity began to be formed in the solid dispersion.

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The tautomerism between a hydroxy Schiff base (I), the titled compound, and the corresponding ring-closed oxazolidine (II) was kinetically studied in solution. In chloroform, the rates of tautomerism (I⇄^^k₁__k₂) were determined using NMR and UV spectroscopies, and both methods gave the almost identical pseudo first-order rate constants (k_obs=k₁+k₂) of 5.4×10^-4s^-1. The ratio of I to II at equilibrium, estimated by an NMR method in chloroform-d₁, was 1 : 1 and 7 : 1 in methanol-d₄.The molecular species of compound I in various pH buffers were deduced by NMR, UV and other spectroscopies. In an acid solution (e.g., pH 3.0) compound I existed as the protonated Schiff base (IH⁺) at the imine nitrogen atom, and in the alkaline region (e.g., pH 9.0) as the oxazolidine form II. The tautomerism rates in the aqueous solutions were measured by a pH-jump method using a stopped-flow apparatus. The rate (I⇄II) in the alkaline region was faster than that (IH⁺ ⇄ IIH⁺) in the acid region, where IIH⁺ represents an N-protonated oxazolidine form of II.

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An equation for the dissolution of a monodisperse system with an optional initial amount was derived from the Nernst equation. The derived equation was given as a function of the initial amount used for the dissolution test, and was expressed by a form which included the cube root law and negative two-thirds root law equations. Hence, the derived equation is herein abbreviated as the z-law equation following the cube root law and negative two-thirds root law equations. The dissolution measurements of monodisperse crystalline particles using various initial amounts within the amount required to saturate the solution were carried out, and these dissolution processes were treated by use of the z-law equation. The applicability or validity of the z-law equation for the dissolution of monodisperse crystalline particles with optional initial amounts was estimated by a simulation of the dissolution process. As a result, it was suggested that the z-law equation more efficiently explains the dissolution process than the cube root law equation for the treatment of dissolution under sink condition. Also, applicability of the z-law equation was fairly good for dissolution under non-sink condition. Hence, the derived general dissolution equation, i.e., the z-law equation, was thought to be efficient for the treatment of dissolution of a monodisperse system with optional initial amounts within solubility.

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Solid dispersion (SD) was prepared with a slightly water soluble medicine (flurbiprofen (FP)) and a water soluble polymer (hydroxypropyl cellulose (HPC)) having five grades of different molecular weights. The release mechanism of FP from the SD granules and the interaction between FP and HPC in the SD were studied.The release rate of FP from the SD granules increased with decreasing HPC molecular weight or increase in the composition ratio of HPC. The powder X-ray diffraction patterns and DSC curves suggest that FP exists in an amorphous state in the SD. The IR spectra show an interaction of hydrogen bonding between FP and HPC. The percent of FP forming a hydrogen bond with HPC in the SD increased with decreasing HPC molecular weight or increase in the composition ratio of HPC. A linear relationship was found between the release rate of FP and the percent of the hydrogen bonded FP in the SD. An increase in the dispersibility of FP and the degree of mixing of FP and HPC will cause an increase in the effective surface area of FP and HPC for dissolution, thus increasing the release of FP and the percent of hydrogen bonded FP.

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For the design of multiparticulate Time-Controlled Explosion System (TES), the thickness of the swelling agent layer was optimized by determining the amount of drug released. Low-substituted hydroxypropylcellulose (L-HPC) was used as a swelling agent. At 120 μm thickness, tiapride hydrochloride was released before the membrane destruction, while at 180 μm thickness the drug release was completed within 30 min after the destruction. Similar results were obtained for TES containing metoclopramide hydrochloride. These results suggest that the L-HPC layer must be at least 180 μm thick. To evaluate the effect of solubility of the drug on release behavior, sodium diclofenac and nilvadipine were used as typical model drugs with an acidic functional group and poor solubility, respectively. The release studied were performed for these drugs in TES with 180 μm L-HPC layer. It is demonstrated that TES can provide a constant drug release profile, regardless of the solubility of a drug and dissolution conditions. In the case that L-HPC layer was fixed at a thickness of 180 μm, the release of diclofenac was not influenced by drug content.

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To describe lag time of Time-Controlled Explosion System (TES), the system's water absorption kinetics was investigated. Study of water absorption in TES with EC membrane revealed the following relations : (i) the square of water-uptake linearly increased with time in accordance with the Washburn equation, (ii) the water permeation rate correlated with the reciprocal of membrane thickness, (iii) the amount of water-uptake necessary for membrane destruction was directly proportional to the thickness of the membrane. These results suggest that lag time of TES is regulated by the function of membrane thickness. Indeed, the observed lag time was confirmed to fit with the curve expected by the above relations. When talc was included in the EC membrane in an equal weight ratio as a membrane-filler, lag time related directly to the membrane thickness. Compared with TES consisting of EC membrane only, the membrane was destroyed by a smaller amount of uptaken water owing to the weakening of membrane strength by the talc addition.

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The structure of the complex [Cu₄OCl₆(cpz)₄](C₆H₆)₆, produced from the reaction between chlorpromazine (cpz) and Cu(II)Cl₂ in the presence of a small amount of water, was determined by X-ray diffraction analysis. The complex crystallizes in the monoclinic space group P2₁/a with a=66.807(3), b=16.767(2), c=9.6484(4)Å, β=95.725(3)°, V=10754(1)ų, and Z=4. Each copper atom in the core (Cu₄OCl₆) is coordinated by a cpz ligand through the terminal nitrogen atom of the side-chain.

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3-Chloropyridazine-6-carboxylic acid hydrazide (5) was synthesized by employing hydrazine monohydrate and methyl levulinate as starting materials through five steps, including hydrozinolysis. Selective hydrazinolysis of 3, 6-substituted pyridazines was investigated.

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Reaction of N'-phenylthioformohydrazide with carbonyl compounds, such as aliphatic, aromatic and heterocyclic aldehydes and a ketone, in the presence of trimethylsilyl chloride proceeded easily to afford the corresponding 2, 2'-substituted-2, 3-dihydro-3-phenyl-1, 3, 4-thiadiazoles in good yields under mild conditions.

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The condensation reaction under acid condition of the benzylic alcohols 1, 2 and 3 with the hexadeutero dimethoxybenzenes 4, 5 and 6 leads to the expected hexadeutero bis(dimethoxyphenyl)-2-methylpropanes 7, 8 and 9, respectively. However, the presence of both dodecadeutero and unlabelled 1-bis(2, 4-dimethoxyphenyl)-2-methylpropanes 10 and 11 indicates that 9 undergoes a rapid degenerate dealkylation-alkylation reaction.

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From the leaflets of Dryopteris crassirhizoma, a new triterpenoid hydrocarbon, trisnorhopane (1) was isolated together with fern-7-ene (2), neohop-12-ene (3), fern-9(11)-ene (4) and hop-22(29)-ene (5). Compound 1 was also isolated from the leaflets of Gleichenia japonica, together with 4, 5 and neohop-13(18)-ene (6). The structure of 1 was elucidated on the basis of spectral data.

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A biodegradation product of betulin was isolated from decayed outer bark of Betula platyphylla SUKATCHEV var. japonica(MIQ.) HARA. The structure was elucidated as (17R, 20R)-7β, 20, 23, 29-tetrahydroxy-28-norlupane-3, 16-dione by chemical and spectral means.

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The Dimroth rearrangement of 7-alkyl-1-methyladenines (8) to produce 7-alkyl-N⁶-methyladenines (9) (63-72% yield) has been found to be accompanied with unusual hydrolytic deaminations to give 7-alkyl-1-methylhypoxanthines (10) (1-3.5%) and/or 7-alkylhypoxanthines (11) (12-22%), when effected in boiling H₂O for 4-70 h. Probable pathways leading to these by-products are proposed.

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Four positional isomers of 6¹, 6ⁿ-di-O-(tert-butyldimethylsilyl)-cyclomalto-octaose (n=2-5) were prepared by reaction of cyclomalto-octaose (1, cG₈) with tert-butyldimethylsilyl chloride in pyridine, and were isolated by high-performance liquid chromatography. The regiochemical determination of those positional isomers was performed by comparison with authentic compounds, prepared from 6¹, 6ⁿ-di-O-trityl-cG₈s (n=2-5).

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Squamosten-A, a new mono-tetrahydrofuranic acetogenin possessing a double bond in the hydrocarbon chain, has been isolated from the seeds of Annona squamosa L. (Annonaceae). The structure has been elucidated on the basis of spectral evidence, including precursor-ion scanning spectra. Chemical degradation was successfully employed to determine the position of the double bond.

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The synthesis of some novel quaternary ammonium salts, derivatives of 15-phenyl-decapentanoic acid, is described. Their lipophilicity was estimated applying the Hansch-Leo fragmental procedure and measured by means of reversed phase thin layer chromatography. All compounds were tested for their antibacterial activity against Gram positive and gram negative microorganisims. The less lipophilic compounds showed weak activity, mainly against gram positive microorganisms.

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An assay method for the determination of curculigoside in Curculiginis Rhizoma by high performacne liquid chromatography (HPLC) was set up. After extraction with ethyl acetate, curculigoside was hydrolyzed in 1 N NaOH, and quantitatively converted to 2, 6-dimethoxybenzoic acid (2, 6-DA). The determination of curculigoside in Curculiginis Rhizoma was performed indirectly by measuring the content of 2, 6-DA by HPLC. The calibration curve for this method exhibited a good linearity with a correlation coefficient of 1.0000 over the concentration range 1.0 to 81.0 μg 2, 6-DA/ml (from 3 to 207 μg/ml as curculigoside). Using this method, 7 lots of Curculiginis Rhizoma produced in China contained about 0.2% curculigoside on average. To estimate the reliability of this method, the curculigoside content of Curculiginis Rhizoma was determined by direct assay applying the HPLC method and using curculigoside as the standard. Both methods agreed very well and this method was found to be satisfactory for estimating the contents of curculigoside in Curculiginis Rhizoma.

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^2H-NMR spectra and the relaxation time of deuterium oxide adsorbed on some pharmaceutical excipients were measured using a high resolution NMR spectrometer in order to clarify the effect of the binding of water to some pharmaceutical excipients on drug decomposition. The decomposition rate of cephalothin was determined in the presence of corn starch and MCC as model excipients under various humidity conditions. The decomposition rate increased with the increasing water content of the excipients. The spin-lattice relaxation time increased with increasing water content similarly to the decomposition rate. This suggests that the ²H-NMR spin-lattice relaxation time can be used as a measure of the water mobility which affects the decomposition rate of drugs in the solid state.

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The reduction of organic functionalities with a samarium or ytteribium metal-hydrochloric acid system was investigated. Carboxylic acid, ester, amide and nitrile were rapidly reduced to the corresponding alcohol or primary amine with samarium or ytteribium metal in the presence of hydrochloric acid at room temperature under an argon atmosphere in good yields. Carboxylic acid was similarly reduced to alcohol with a magnesium or yttrium-hydrochloric acid system.

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Optically active 5-hydroxymethylcyclohexenones and 5-acetoxymethylcyclohexenones were efficiently obtained by enzymatic enantioselective esterification and chemical conversion.

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A new mutagen, 2-amino-1, 7, 9-trimethylimidazo[4, 5-g]quinoxaline (1), isolated from beef extract, was synthesized from 3-fluoro-2-methylaniline via an intermediate, 2, 8-dimethyl-7-methylaminoquinoxaline (7a). Its 2-methylanalog (2) was also synthesized from the same intermediate. The synthetic 1 showed the same mutagenic activity as the isolated mutagen. However, 2 was non-mutagenic.

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The first total synthesis of optically active fucoxanthin 1 has been accomplished via the 8-oxo-compound 7, efficiently prepared by rearrangement of the α-acetylenic alcohol 2 using oxo-metallic catalyst and subsequent iodine catalyzed double bond-shift.

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1-Chlorophthalazine reacts with two molar of ynamines to give penta-substituted pyridine derivatives by N-N bond cleavage of phthalazine ring. We realize this is common to other halo-substituted condensed pyridazines.

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A novel synthesis of the quinazolinequinone (5) and the carbazolequinone (9) is described. Anionic cycloaddition of the heterocyclic esters (1 and 6) with phenyl β-trimethylsilylvinyl sulfone (2c) afforded the cycloadducts (3 and 7), which were converted to the quinones (5 and 9) via the phenols (4 and 8). This method was applied to a covenient synthesis of murrayaquinone A (10).

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N, O-Diacylhydroxylamines rearrange under basic conditions to afford 2, 3-disubstituted succinic acid derivatives. The rearrangement can be rationalized in terms of [3, 3]sigmatropic shifts of ester-amide dienolated N, O-diacylhydroxylamines.

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