Five new naturally occurring monoterpenoids, crocusatins-A (1), -B (2a), -C (3), -D (4a) -E (5), a new lactate, sodium (2S)-(O-hydroxyphenyl)lactate (6), and eighteen known compounds were isolated and characterized from the pollen of Crocus sativus L. The tyrosinase inhibitory activities of these compounds were also discussed.

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After a series of optimization for the reaction conditions (reagents, reaction temperature, etc.), treatment of the sulfonates 4, 8, 13 and 15 with 8% NaOH (room temperature, 24 h) via a semipinacol rearrangement afforded the corresponding C-nor compounds 5, 9, 12 and 16, as the major of a pair of epimer at C-16, to an excellent extent, in 95%, 92%, 100% and 90% yield, respectively. The 12,13-seco compounds 21 and 22 (23) were obtained in 20% and 60% yield, respectively, by treating 5 with Br₂–glacial HOAc (room temperature, 24 h). Treatment of the C-nor compounds 5 or 6, 16 or 17, and 28 from 10 with SOCl₂–anhydrous benzene (room temperature, overnight) afforded the 12,13-seco compounds 24, 26 and 30 in 70% or 100%, 40% and 66% yield, respectively. When treatment of the C-nor compound 29 from 9 under same conditions gave the 12,13-seco products 30, 31 and 32 in 33%, 26% and 20% yield. When treating 21 or 24, and 26 with 5% KOH in EtOH afforded the 12,13-seco compounds 25 and 27 quantitatively, respectively. The compound 31 converted to 30 quantitatively by treatment with Na₂CO₃ in MeOH. All of the new compounds were isolated and fully characterized.

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The first synthesis of (αS,βS)-β-hydroxy-α-[(methoxycarbonyl)amino]-4,6-dimethyl-9-oxo-3-β-D-ribofuranosyl-4,9-dihydro-3H-imidazo[1,2-a]purine-7-butanoic acid methyl ester [(αS,βS)-11] has been achieved by OsO₄ oxidation of [S-(E)]-4-[4,6-dimethyl-9-oxo-3-[2,3,5-tris-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-4,9-dihydro-3H-imidazo[1,2-a]purin-7-yl]-2-[(methoxycarbonyl)amino]-3-butenoic acid methyl ester (13) followed by successive γ-deoxygenation through the cyclocarbonates, separation from the (αS,βR)-isomer by means of flash chromatography, and deprotection. On the other hand, the minor nucleoside of rat liver tRNA^Phe was isolated on a scale of 100 μg by partial digestion of unfractionated tRNA (1 g) with nuclease P₁, followed by reverse-phase column chromatography, complete digestion with nuclease P₁/alkaline phosphatase, and reverse-phase HPLC. Comparison of this nucleoside with the synthetic one has unambiguously established its structure to be (αS,βS)-11.

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Epimeric 3α,7α,16- and 3α,7α,15-trihydroxy-5β-cholan-24-oic acids and some related compounds were synthesized from chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), respectively. The key reaction involved one-step remote oxyfunctionalization of unactivated methine carbons at C-17 of CDCA and at C-14 of UDCA as their methyl ester-peracetate derivatives with dimethyldioxirane (DMDO). After dehydration of the resulting 17α- and 14α-hydroxy derivatives with POCl₃ or conc. H₂SO₄, the respective Δ¹⁶- and Δ¹⁴-unsaturated products were subjected to hydration via hydroboration followed by oxidation to yield the 3,7,16- and 3,7,15-triketones, respectively. Stereoselective reduction of the respective triketones with tert-butylamine-borane complex afforded the epimeric 3α,7α,16- or 3α,7α,15-trihydroxy derivatives exclusively. A facile formation of the corresponding ε-lactones between the side chain carboxyl group at C-24 and the 16α- (or 16β-) hydroxyl group in bile acids is also clarified.

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The effects of steam sterilization and γ-irradiation on chitosan and thermogelling chitosan-β-glycerophosphate (GP) solutions containing polyol additives were investigated. The selected polyols were triethylene glycol, glycerol, sorbitol, glucose and poly(ethylene glycol) (PEG). They were incorporated to chitosan solutions prior to sterilization in a proportion ranging from 1 to 5% (w/v). The solutions were characterized with respect to their viscosity, thermogelling properties, compressive stress relaxation behavior and chitosan degradation. All polyols reduced the autoclaving-induced viscosity loss and had a positive impact on the solution thermogelling properties and compressive performance of the gels. Steam sterilization in the presence of glucose resulted in a substantial increase in the solution viscosity and gel strength. This was associated with a strong discoloration suggesting chemical alteration of the system. PEG was the most effective agent in preventing hydrolytic degradation of chitosan chains. Gamma-irradiation strongly decreased the chitosan solution viscosity regardless of the presence of additives, even when sterilization was carried out at −80 °C. Moreover, the thermogelling properties were dramatically altered, and thus, γ-irradiation would not be an appropriate method to sterilize chitosan solutions. In conclusion, polyols are potentially useful additive to maximise the viscoelastic and mechanical properties of chitosan-GP after steam sterilization.

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Hyaluronate-hydroxyethyl acrylate blend gel (HA-PHEA) were prepared to modify the brittleness of hyaluronate gel (HA) and the characteristics of HA-PHEA gel were compared with those of HA and polyhydroxyethyl acrylate (PHEA) gels. These gels were high in water content and transparent. HA-PHEA gel was improved in viscoelastic properties due to the elasticity and the high affinity with water of PHEA, and the drying-swelling cycles became reversible. The effective charge densities θ of the gels estimated from membrane potentials were −0.002, −0.008 and 0 mol dm⁻³ for HA-PHEA, HA and PHEA gels. Effects of electro- static and nonelectrostatic interactions on absorptions and releases were studied using sodium benzoate (NaBA) as an anionic solute, and methylene blue (MB), chlorpromazine (CPHCl) and benzethonium chloride (BZTCl) as cationic solutes, in which CPHCl and BZTCl are cationic amphiphilic solutes. The releases of MB, CPHCl and BZTCl from HA-PHEA and HA gels were suppressed comparing with those of NaBA. By adding salts, the releases of MB and CPHCl were enhanced but those of BZTCl were suppressed due to enhancement of the intra- and intermicelle formation. In the releases of the cationic solutes from HA-PHEA gel, electrostatic and nonelectrostatic interactions with HA were found to play important roles. Behaviors of the releases from HA-PHEA gel were found to possess the features of HA gel.

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A novel series of oxyiminoacetic acid derivatives were synthesized in an effort to develop a potent antidiabetic agent, which does not contain the 2,4-thiazolidinedione moiety. These compounds were evaluated for glucose and lipid lowering effects in genetically obese and diabetic KKA^y mice. Several of the compounds showed strong antidiabetic activity, including functional potency at peroxisome proliferator-activated receptor (PPAR)-γ. (Z)-2-[4-[(5-Methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]benzyloxyimino]-2-(4-phenoxyphenyl)acetic acid (25) significantly reduced plasma glucose (33%, p<0.01) and plasma triglycelide levels (43%, p<0.01) even at a dosage of 0.001% in diet. Pharmacokinetic analyses of 25 are also reported.

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Two new phenol glucosides termed juniperosides I (1) and II (2) were isolated, together with known two biflavones, cupressuflavone and amentoflavone and a diterpene, 3β-hydroxy sandaracopimaric acid, from leaves of Juniperus occidentalis HOOK. (Cupressaceae) collected in Oregon, U.S.A., and their structures were established as (1S)- and (1R)-1-(2′-hydroxy-6′-methylphenyl)ethanol 2′-O-β-D-glucopyranosides (1, 2), respectively, on the basis of spectral, chemical, and synthetic evidence. The glycosides 1 and 2, as well as the corresponding aglycones 1a and 2a, are apparently novel types of naturally occurring compounds; to our knowledge, isolation of these types of natural phenol derivatives has only rarely been reported from the vegetable kingdom.

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To synthesize optically active 2-amino-2-methyl-3-phenylpropanoic acid (1), (RS)-2-benzoylamino-2-benzyl-3-hydroxypropanoic acid [(RS)-2] was first optically resolved using cinchonidine as a resolving agent to yield optically pure (S)- and (R)-2 in yields of about 70%, based on half of the starting amount of (RS)-2. Next, the racemic structure of (RS)-2 was examined based on melting point, solubility, IR spectrum, and binary and ternary phase diagrams, with the aim of optical resolution by preferential crystallization of (RS)-2. Results indicated that the (RS)-2 exists as a conglomerate at room temperature, although it forms a racemic compound at the melting point. The optical resolution by preferential crystallization yielded (S)- and (R)-2 with optical purities of about 90%, which were fully purified by recrystallization. After O-tosylation of (S)- and (R)-2, reduction by zinc powder and sodium iodide gave (R)- and (S)-1, respectively.

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Two new isoflavones, 6, 3′, 4′-trimethoxy-7, 8, 5′-trihydroxyisoflavone (1), 7, 4′-dimethoxy-8, 3′, 5′-trihydroxy-6-O-β-D-glucopyranosylisoflavone (2), and 5, 3, 3′-trihydroxy-7, 4′-dimethoxyflavanone (3) have been isolated from the underground parts of Iris potaninii along with known isoflavones (4—8) and iriflophenone (9). The structures of the new compounds were determined using NMR and mass spectroscopic methods.

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We examined the enhancement effects of the double-chained cationic surfactants of n-dimethyldialkylammoniums (CH₃)₂N⁺(C_nH_2n+1)₂ on the permeation of anionic salicylate through excised guinea pig dorsal skin at pH 7.4. Among them, n-dimethyldidecylammonium (2C10), which seemed to form micelles, had dose-dependent enhancement effects at concentrations of more than 0.1 mM, and about a ninety-fold increase in the permeability coefficient of salicylate was observed at 2 mM. The enhancement effect of 2C10 was larger than those of single-chained cationic surfactants of n-alkyltrimethylammoniums. n-Dimethyldilaurylammonium (2C12), which seemed to form bilayer vesicles, induced about a twenty five-fold increase in the permeability coefficient. The enhancement effects of n-dimethyldialkylammoniums decreased with the increase in their alkyl chain lengths. In contrast, only slight stimulation by these cationic surfactants was observed for silicon rubber membrane permeation of salicylate. Analysis of the retention of the salicylate in the skin suggested that the double-chained cationic surfactants-induced increase in the transfer of salicylate to the skin is the main reason for the marked stimulation of the skin permeation.

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In boiling aqueous solution, D-amygdalin usually begins to convert into neoamygdalin in 3 min and more than 30% of the initial D-amygdalin is found as neoamygdalin after 30 min. In this report, we establish methods for simple HPLC analysis and the inhibition of D-amygdalin conversion. D-Amygdalin and its conversion product, neoamygdalin, were clearly separated on reverse-phase column chromatography by an optimized eluent of 10 mM sodium phosphate buffer (pH 3.8) containing 6% acetonitrile. Linearity for analyzing D-amygdalin and neoamygdalin was observed in the range from 0.05 to 0.5 mM. The detection limits for D-amygdalin and neoamygdalin were ca. 5 μM per injected amount. We found that D-amygdalin conversion was completely inhibited by adding 0.05% citric acid to the aqueous solution before boiling. To prevent the loss of pharmaceutical potency of Tonin, we applied this method to measure the conversion rate of D-amygdalin. We confirmed that D-amygdalin conversion in Tonin is effectively inhibited by acidic boiling solution with 0.1% citric acid.

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The structure including the absolute configuration of a new glucoalkaloid, 3,4-dehydro-5(S)-5-carboxystrictosidine, isolated from Peruvian Uña de Gato (Cat's Claw, original plant: Uncaria tomentosa), was confirmed by synthesis starting from secologanin and L-tryptophan.

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A new and general method is described for the synthesis, in three steps and in good overall yields, of tetrasubstituted xanthines from an easily prepared imidazole precursor. The method is especially useful for the preparation in standardized conditions of series of xanthines combining a broad variety of primary or secondary alkyl, benzyl or aryl groups at N1 and of alkyl or arylmethyl groups at N3, that are not readily available by other methods.

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A novel lupane-triterpene glycoside, called wujiapioside B (1), was isolated from the leaves of Acanthopanax gracilistylus (Araliaceae) together with three known lupane-triterpene glycosides, acankoreoside C (2), acantrifoside A (3) and 3-epibetulinic acid 28-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl ester (4). Based on spectroscopic data, the chemical structure of 1 was determined as 3α,23-dihydroxy-lup-20(29)-en-28-oic acid 28-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl ester. Compounds 2—3 were obtained for the first time from this plant and compound 4 has not been isolated from Acanthopanax genus yet.

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Two monomethylated GM₃-Type ganglioside molecular species, 1 and 2, have been obtained from the polar lipid fraction of the chloroform/methanol extract of the starfish Luidia maculata. The structures of these gangliosides have been determined on the basis of chemical and spectroscopic evidence as 1-O-[8-O-methyl-(N-acetyl-α-D-neuraminosyl)-(2→3)-β-D-galactopyranosyl-(1→4)-β-D-glucopyranosyl]-ceramide (1) and 1-O-[8-O-methyl-(N-glycolyl-α-D-neuraminosyl)-(2→3)-β-D-galactopyranosyl-(1→4)-β-D-glucopyranosyl]-ceramide (2). The ceramide moieties were composed of heterogeneous unsubstituted fatty acid, 2-hydroxy fatty acid, sphingosine and phytosphingosine units. Compound 1, designated as LMG-3, represents new ganglioside molecular species. Compound 2 was a known ganglioside molecular species.

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The ether extract of the New Zealand liverwort Radula marginata afforded a new cannabinoid type bibenzyl compound named perrottetinenic acid, and two new bibenzyls, together with a known cannabinoid, perrottetinene. Their structures were established by two dimensional (2D) NMR spectral data. The structure of perrottetinenic acid was a similar to that of Δ¹-tetrahydrocannabinol, a known hallucinogen. Cannabinoid type bibenzyls have been isolated from liverwort Radula perrottetii, though have not previously been reported from the liverwort R. marginata.

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A new alkaloid, 1,2,3,9-tetrahydropyrrolo(2,1-b)quinazolin-1-carboxylic acid (1), together with eight known compounds, 7-hydroxy vasicine (2), benzyl alcohol β-D-(2′-O-β-xylopyranosyl)glucopyranoside (3), benzyl alcohol O-β-D-glucopyranoside (4), benzyl alcohol O-β-D-primveroside (5), 3,5-dimethyl-4-hydroxy benzaldehyde (6), gluco-syringic acid (7), syringin (8), and liriodendrin (9), were isolated from the plants of Linaria vulgaris. Their structures were established by spectroscopic methods.

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A new iridoid glucoside dimer (1) and a non-glycosidic iridoid (2) was isolated together with the known compounds, asperuloside (3), paederoside (4), daphylloside (5), citroside A (6) and benzyl 6-O-α-L-rhamnopyranosyl-β-D-glucopyranoside (7), from the leaves of Lasianthus wallichii. The structures of the new compounds were elucidated by spectroscopic and chemical evidence.

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A new method for the synthesis of 7-deoxytaxane analogues has been established through hydrogenation of Δ^6,7-taxane derivatives. Among several catalysts examined, Pd–C was found to be a most effective catalyst for the preparation of target compound.

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Ten Tyr-D-Arg-Phe-βAla-NH₂ (YRFB) analogs in which specific amino acid side chains are shifted to the N^α-position were synthesized, and the binding to these analogs to the μ receptor and their in vitro biological properties were evaluated. Some analogs in which a N,N-bis(p-hydroxybenzyl)-Gly residue was substituted for Tyr¹ exhibited μ receptor antagonist activities (pA₂) between 5.3 and 6.1. Of these analogs, [N,N-bis(p-hydroxybenzyl)-Gly¹]YRFB was found to be the most potent specific antagonist for the μ-opioid receptor.

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Novel, enantiomerically pure organoantimony compounds having a C-chiral amine moiety, (S)-(α-methyl-2-di-p-tolylstibanobenzyl)dimethylamine [AMSb] (2) and its (η⁶-arene)chromium complex [AMSb–Cr(CO)₃] (4), were prepared from common (S)-(α-methylbenzyl)dimethylamine (1) via its ortho-lithiated intermediates in short steps. The catalytic activity and enantioselectivity of the ligands 2 and 4 for asymmetric reaction are evaluated, and the optically active (η⁶-arene)chromium complex 4 has been shown to be an effective ligand for rhodium-catalyzed asymmetric hydrosilylation of ketones.

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An efficient and practical procedure for the synthesis of esonarimod, (R,S)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (1), a new antirheumatic drug, has been developed. The intermediate, 2-methylene-4-(4-methylphenyl)-4-oxobutanoic acid (2), was prepared by Friedel–Crafts acylation of toluene with itaconic anhydride (3) in the presence of aluminum trichloride and nitrobenzene in 63% yield without silica gel column purification. Compound 1 was prepared by Michael addition of 2 with thioacetic acid (4) in 74% yield. Overall, 1 was obtained in 47% yield from 3. The structures and synthetic mechanisms of by-products (five compounds) of 2 were also clarified.

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A new megastigmane glycoside, called pipeloside A, and a new aromadendrane type sesquiterpenoid, pipelol A, were isolated from the MeOH extract of the aerial part of Piper elongatum VAHL. along with a known megastigmane glycoside, byzantionoside B. The structures of these compounds were elucidated on the basis of spectroscopic data and chemical evidence.

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A new ortho-benzoyloxyphenyl acetic acid ester, called vaccihein A (1), was isolated from the fruit of rabbiteye blueberry (Vaccinium ashei). The chemical structure was determined on the basis of spectroscopic data. Compound 1 had antioxidative activity using the ferric thiocyanate method. In addition, 1 showed a scavenging effect on the stable free radical 1,1-diphenyl-2-picrylhydrazyl.

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CX-659S (1) [(S)-6-amino-5-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)-3-methyl-1-phenyl-2,4-(1H,3H)-pyrimidinedione], has been developed as a new type anti-inflammatory agent for the treatment of dermatitis. The structure of a major metabolite of CX-659S was determined as (S)-6-amino-5-[2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxo-1,4-cyclohexadienyl)butanamide]-3-methyl-1-phenyl-2,4-(1H,3H)-pyrimidinedione (2) by direct comparison with the synthesized authentic compound. The anti-inflammatory activity of 2 was equipotent with that of 1 on the contact hypersensitivity reaction (CHR) induced by picryl chloride (PC) in mice, suggesting that compound 2 contributes, at least in part, to the anti-inflammatory activity of CX-659S.

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The biomimetic reduction of anti-inflammatory drug, nimesulide (1) with sodium borohydride catalyzed by 5,10,15,20-tetraarylporphyrinatoiron(III) chlorides [TAPFe(III)Cl] has been studied in organic solvents under anaerobic and aerobic conditions.

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