The charge-transfer complex formed by the interaction between the electron acceptor, p-chloranilic acid and an electron donor diethylcarbamazine was adopted for the assay of the drug in pure powder and in tablets. In dioxane-chloroform medium, chloranilic acid was found to form a 1 : 1 molecular complex with diethylcarbamazine with maximum absorption band at 540 nm. At 540 nm, the absorbance was linear (γ=0.9999) over the concentration range of 10-400 μg/ml. The pertinent equilibrium constants and molar absorptivities were calculated at different temperatures using the Scott equation and were found to decrease with increase in temperature. The free energy change (ΔG°) and the enthalpy of formation (ΔH°) as well as the entropy (ΔS°) were determined for the various interactions. The proposed method has been conveniently applied in the analysis of commercially available diethylcarbamazine citrate tablets with good accuracy and precision.

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A series of Al, Ti, Zn and Zr compounds, i.e., their metal alkoxides, organic acid and enolate salts, halid and oxide, were evaluated as intramolecular transesterification catalysts for the thermal depolymerization reaction of poly(L-lactic acid) oligomer resulting in LL-lactide, meso-lactide and DD-lactide by gas chromatography using a β-cyclodexstrin chiral stationary phase capillary column. The activity of the intramolecular transesterification compared with that of stannous 2-ethylhexanoate was in the following order : Sn>Zn>Zr>Ti>Al.

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Two new pyrrolidine alkaloids, broussonetines K and L, were isolated from the branches of Broussonetia kazinoki SIEB. (Moraceae). Broussonetines K and L were formulated as (2R, 3R, 4R, 5R)-2-hydroxymethyl-3, 4-dihydroxy-5-[(1R)-1-hydroxy-10-oxo-13-(β-D-glucopyranosyloxy) tridecyl] pyrrolidine (1) and (2R, 3R, 4R, 5R)-2-hydroxymethyl-3, 4-dihydroxy-5-[(1R)-1-hydroxy-9-oxo-13-(β-D-glucopyranosyloxy) tridecyl] pyrrolidine (2), respectively, by spectroscopic and chemical methods. 1 and 2 inhibited β-glucosidase, β-galactosidase and β-mannosidase.

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Four new withanolide glycosides (1-4) have been isolated from Physalis peruviana. Their structures were established as (20R, 22R)-1α-acetoxy-14α, 20-dihydroxywitha-5, 24-dienolide-3β-(O-β-D-glucopyranoside) (1), (20S, 22R)-1α-acetoxy-27-hydroxywitha-5, 24-dienolide-3β-(O-β-D-glucopyranoside) (2), (20R, 22R)-20, 27-dihydroxy-1-oxowitha-5, 24-dienolide-3β-(O-β-D-glucopyranoside) (3), and (20R, 22R)-14α, 20, 27-trihydroxy-1-oxowitha-5, 24-dienolide-3β-(O-β-D-glucopyranoside) (4) on the basis of spectroscopic data including two dimensional NMR techniques and through chemical transformations.

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A novel series of indolebutyric acids with varying benzoyl substituents were synthesized to develop nonsteroidal inhibitors of steroid 5α-reductase. We previously reported the discovery of a novel nonsteroidal 5α-reductase inhibitor, FR119680, which had an IC₅₀ value of 5.0 nM against the rat prostatic enzyme. However, this compound was not strongly active against the human prostatic enzyme. By further study of the structure-activity relationships we succeeded in producing the strongly active compound, FK143, 4-[3-[3-[bis(4-isobutylphenyl)-methylamino]benzoyl]-1H-indol-1-yl]butyric acid, with an IC₅₀ value of 1.9 nM against the human enzyme. FK143 also has in vivo inhibitory activity against the castrated young rat model and it should therefore be an extremely useful agent for the treatment of benign prostatic hyperplasia.

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To prevent temperature-dependent gel-sol transformation of an o/w emulsion type new vehicle system for a soft gelatin capsule, which may be available for both preclinical and clinical trials, the basic new vehicle formulation (PEG 400 : purified water : medium chain triglyceride : polyoxyethylene (20) cetylether=77 : 10 : 10 : 3) was modified by partially (1, 2 or 3%) replacing PEG 400 with PEG 6000 or PVP K30.When 2 or 3% of PEG 400 was replaced with PEG 6000, temperature-dependent gel-sol transformation was prevented at temperatures below 40 °C, and the vehicle appeared to be stable during 8 weeks of storage at 4 to 40 °C; the particle size distribution remained unchanged. When 1% of PEG 400 was replaced with PEG 6000, gel-sol transformation was not prevented, though phase separation was not observed at sol state, and the particle size distribution was shifted to be in a larger particle size range after 2 weeks of storage.When PEG 400 was partially (1, 2 or 3%) replaced with PVP K30, temperature-dependent gel-sol transformation was not prevented and, after 2 weeks of storage at 40 °C, the particle size distributions of the vehicles were shifted to be in a larger particle size range and the vehicles were separated into two layers.These results suggested that a small amount of PEG 6000 plays an important role in preventing temperature-dependent gel-sol transformation of our developed vehicle system.

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Five new taraxastane-type triterpenes, 22-oxo-20-taraxasten-3β-ol (1), 20(30)-taraxastene-3β, 21α-diol (2), 20α, 21α-epoxytaraxastan-3β-ol (3), 20-taraxastene-3β, 22β-diol (4), and 3β-acetoxy-20-taraxasten-22-one (5), together with 20-taraxasten-3β-ol (6) and ptiloepoxide (7) were isolated from the aerial roots of Ficus microcarpa.Their structures were elucidated by spectroscopic and chemical methods.

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The present study was undertaken to evaluate whether a novel series of 2, 6-diaza-5-oxobicyclo[5.4.0]undeca-1(7), 8, 10-triene derivatives exhibited antagonistic activity for vasopressin V₁ and V₂ receptors. Most of these compounds were synthesized and showed a high affinity potential for V₂ receptor and low to moderate affinity potential for V₁ receptor. The most potent and V₂-selective compound, N-[4-[2, 6-diaza-6-[2-(4-methylpiper-azinyl)-2-oxoethyl]-5-oxobicyclo[5.4.0]undeca-1(7), 8, 10-trien-2-yl]-carbonyl]phenyl][2-(4-methylphenyl)phenyl]-formamide (11b), exhibited IC₅₀'s of 2.9 nM for the V₂ receptor and 200 nM for the V₁ receptor, respectively.When administered orally to rat, 11b showed an approximately 18-fold increased urine volume in comparison with control rat.

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Twelve new cyclolanostanol glycosides (1-12) were isolated from the underground parts of Cimicifuga simplex WORMSK. (Ranunculaceae) together with five known cyclolanostanol glycosides (13-17). On the basis of spectral and chemical evidence, the structures of 1-12 were determined to be 24-epi-24-O-acetyl-7, 8-didehydrohydroshengmanol 3-O-β-D-xylopyranoside and 3-O-α-L-arabinopyranoside, 24-O-acetyl-7, 8-didehydrohydroshengmanol 3-O-β-D-xylopyranoside and 3-O-α-L-arabinopyranoside, 7, 8-didehydrocimigenol 3-O-β-D-xylopyranoside and 3-O-α-L-arabinopyranoside, 25-O-acetyl-7, 8-didehydrocimigenol 3-O-β-D-xylopyranoside and 3-O-α-L-arabinopyranoside, 1α-hydroxycimigenol 3-O-α-L-arabinopyranoside and 3-O-β-D-galactopyranoside, 23-O-acetyl-7, 8-didehydroshengmanol 3-O-β-D-galactopyranoside, and 26-deoxycimicifugoside, respectively. The last compound (12) was also obtained from the underground parts of Actaea asiatica HARA (Ranunculaceae).

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The synthesis of acetomycin and related analogs was investigated. Acetomycin was synthesized from diethyl allyl(methyl)malonate in 6.5% yield over 18 steps. The total number of steps was improved compared to our previous synthesis; i.e., four steps shorter, and the total yield was 4.5% greater than the previous synthesis. Acetomycin analogs with benzoyloxy and pivaloyloxy groups, instead of an acetoxy group at the 5-position of the γ-butyrolactone ring were designed as esterase-resistant models and prepared similarly.Although they showed a similar level of cytotoxicity as acetomycin in vitro, they were not resistant to porcine liver esterase, and lost cytotoxicity in vivo.

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New protostane-type triterpenes termed alisols H, I, J-23-acetate, K-23-acetate, L-23-acetate, M-23-acetate, and N-23-acetate were isolated from Alismatis Rhizoma, the rhizome of Alisma orientale JUZEP. Their stereostructures were determined on the basis of physicochemical evidence.

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We have synthesized a series of novel 1-isoindolinone derivatives, which inhibited the contraction of pig coronary artery induced by U-46619, a thromboxane A₂ analog.

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Seven new tannins, elaeagnatins A-G, have been isolated from the leaves of Elaeagnus umbellata (Elaeagnaceae) together with fifteen known tannins and related polyphenols, and their structures have been characterized as monomeric and dimeric C-glucosidic ellagitannins on the basis of spectral and chemical evidence. Elaeagnatins B, C and F are the first dimers composed of C-glucosidic monomer and ellagitannin monomer with a gluconic acid core.

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Six new migrated hopane triterpenoid alcohols, viz. pteron-14-en-7α-ol (1), fern-9(11)-en-3α-ol (2), fern-7-en-3α-ol (3), adian-5(10)-en-3α-ol (4), adian-5-en-3α-ol (5) and fern-9(11)-en-28-ol (6) were isolated along with many other known triterpenoids from fresh fronds of Adiantum capillus-veneris. Their structures were elucidated by detailed two dimensional-NMR analyses and/or chemical correlations.

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Deoxygenation reaction of steroidal 16, 17-ketols 1, 2 and 6 as well as their silyl ethers 3 and 7 and 16- and 17-iodoketone analogs 11, 12, and 14 with trimethylsilyl iodide (TMSI) or HI under various conditions was examined. The results indicate that the deoxygenation producing 16- and 17-ketones 9 and 8 proceeds through multiple reaction pathways; a direct iodination of a siloxy group of the ketol silyl ethers by iodide ion to give the iodoketones (path b), addition of TMSI to a carbonyl group of the ketol silyl ethers to yield diiodo derivatives 22 and 23 through iodo-bis-TMS compounds 20 and 21 (path a), and cleavage of ether bond of dimers 15-18 initially produced are, at least, involved. In these sequences, rearrangement of the 16-ketols 1 and 2 to the 17β-ketol 6 also plays a significant role. The yields of the ketones 9 and 8 and their relative amounts would be dependent on the relative importance of each pathway in the reaction.

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Methylation of adenine 3-oxide (8a) with MeI in AcNMe₂ afforded 3-emthoxyadenine (9a) in 44% yield. This compound (9a) underwent hydroxide-ion attack at the 2-position to give 2-hydroxyadenine (isoguanine) (10a) in 38% yield. A parallel reaction sequence starting from N⁶-benzyladenine 3-oxide (8c) and proceeding through N⁶-benzyl-3-methoxyadenine (9c) provided N⁶-benzyl-2-hydroxyadenine (10c) in 29% overall yield, together with a small amount of N⁶-benzyladenine (11c).

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The following constituents were isolated from the heartwood of Juniperus chinensis var. tsukusiensis : ar-himachalene (1), 2-himachalen-6-ol (2), 3-himachalen-6-ol (3), 2α, 6α-epoxy-3-himachalene (4), 2α, 6α-epoxyhimachalan-3β-ol (5), and chinensiol (6). Compounds 2-6 are new cis-himachalane-type sesquiterpenes, and their structures were elucidated on the basis of spectral and chemical evidence. Himachalane-type sesquiterpenes were isolated for the first time in Juniperus species.

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Fushioside, a new phenylethanoid glucoside, 2-(3, 4-dihydroxyphenyl)ethyl 6-O-protocatechuoyl-β-D-glucopy-ranoside was isolated from the methanolic extract of the aerial parts of Veronica fuhsii along with a known phenylethanoid glycoside, plantamajoside, and a flavone glucoside, luteolin 7-O-glucoside.

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Conjugates 6 and 7 of cancer peptide antigen with N-tetradecanoly L-serine-β-alanine-containing D-glucosamine derivative structurally related to lipid A as an immunoadjuvant were synthesized for the development of totally synthetic vaccines against cancers. The mitogenic activities of compounds 6 and 7 were stronger than that of lipid A analog 3.

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Pyrogallol cyclic tetramers, tetrasulfonated pyrogallol cyclic tetramers and 25, 27-di(3, 4, 5-trihydroxybenzoyloxy)dihydroxy-calix[4]arene were synthesized. The calix[4]arenes emit light in the presence of hydrogen peroxide in an alkaline medium. Of three calix[4]arenes, 25, 27-di(3, 4, 5-trihydroxybenzoyloxy)dihydroxy-calix[4]arene gave the highest chemiluminescence intensity, and the intensity of the calix[4]arene was 190-fold greater than that of gallic acid in the same solvent.

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Continuing our investigation on the bioactive compounds from the plant of Aristolochia genus in Taiwan, we isolated one new aristolochic acid derivative, aristolochic acid-VII methyl ester; one new dihydrophenanthrenelactone, aristolide-C; four new benzenoids, 2'-hydroxyethyl 4-hydroxybenzoate, ariscucurbin-A, -B and -C, together with forty-six known compounds from the fresh Aristolochia cucurbitifolia.

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Mitsunobu reaction of 2, 6-dichloropurine with 2, 6-difluorobenzyl alcohol gave 2, 6-dichloro-9-(2, 6-difluorobenzyl)-9H-purine and 7-benzylated congener in 73% and 10% yield, respectively. Treatment of the former compound with ammonia gave 2-chloro-9-(2, 6-difluorobenzyl)adenine (1) in good yield. Also, 2-amino-6-chloro-purine was condensed with 2, 6-difluorobenzyl alcohol in a similar manner to afford 2-amino-6-chloro-9-(2, 6-difluorobenzyl)-9H-purine (2) as a major product. Inhibition of phosphodiesterase (PDE) isozymes by 9-(2, 6-difluorobenzyl)-9H-purines was investigated and both 1 and 2 were found to be good inhibitors of PDE2 in addition to PDE4.

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To search for recemization-free coupling conditions for peptides having N-alkylamino acids at the carboxy-termini, a model coupling using Boc-Phe-MeAla-OH (MeAla, N-methylalanine) and H-Phe-OBzl was studied. When benzotriazolyl-N-oxytris(dimethylamino)phosphonium hexafluorophosphate or O-(7-azabenzotriazol-1-yl)-1, 1, 3, 3, -tetramethyluronium hexafluorophosphate was employed as a coupling reagent, no additives so far examined could sufficiently suppress the racemization of the carboxy-terminal MeAla residue. Though N-hydroxy compounds were not satisfactorily effective also in 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSCI)-mediated coupling, CuCl₂ could eliminate the racemization of MeAla in the coupling with WSCI even at room temperature.

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Amphiphilic terpolymer xerogels were prepared from N-isopropyl acrylamide, acrylic acid, and n-dodecyl acrylamide by both chemical redox initiated polymerization and γ-irradiation polymerization. The swelling equilibrium and swelling kinetics of amphiphilic xerogels prepared by these two polymerization methods were compared. Drug release behavior was also compared using 5-fluorouracil (5-FU) as a model drug, in order to elucidate the effect of polymerization method. γ-Irradiation polymerization provided amphiphilic terpolymer xerogels which exhibited slower swelling and drug release than chemical redox initiated polymerization.

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New Polyhydroxylated spirostanol sapogenin (1) and saponin (2) were isolated from the leaves of Cestrum sendtenerianum (Solanaceae). Their Structures were determined to be spirosta-5, 25(27)-diene-1β, 2α, 3β, 12β-tetrol (1) and spirosta-5, 25(27)-diene-1β, 2α, 3β, 12β-tetrol 3-O-β-D-galactopyranoside (2), respectively, on the basis of spectroscopic analysis, including two-dimensional NMR techniques, and the result of hydrolytic cleavage.

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The synthesis and biological evaluation of the dicarba-closo-dodecaborane (carborane) derivatives of retinoids are described. Retinoidal activity was examined in terms of the differentiation-inducing ability toward human promyelocytic leukemia HL-60 cells. High retinoidal activity (agonist or antagonist for the retinoid receptor RAR) requires a carboxylic acid moiety and an appropriate hydrophobic group located at a suitable position on the molecule. 4-[4-(1, 2-Dicarba-closo-dodecaboran-1-yl)phenylamino]benzoic acids and 4-[3-(1, 2-dicarba-closo-dodecaboran-1-yl)phenylamino]benzoic acids showed potent agonistic activity at concentrations of 10^-8-10^-9 M. The results indicate that carboranes are applicable as the hydrophobic moiety of biologically active molecules.

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Secondary imidazole-appended β-cyclodextrin 5 with a nondistorted cavity synthesized from a novel intermediate 3-amino-3-deoxy-β-cyclodextrin exhibits much greater catalytic activity in the ester hydrolysis than its isomer 6 with a distorted cavity, indicating that the catalytic activities of secondary functional cyclodextrins are dependent on cavity structures.

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