New Phenylpropanoid Glycosides from Illicium majus and Their Radical Scavenging Activities

Chemical investigation of the ethanol extract of the branch and leaves of Illicium majus resulted in the isolation of four new phenylpropanoid glycosides ( 1 – 4 ) and one new phenolic glycoside ( 9 ), along with 13 known ones. Spectroscopic techniques were used to elucidate the structures of the new isolates such as 3-[(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-2,3-dihydro-1-benzofuran-5-yl]propyl β-D-glucopyranoside ( 1 ), [(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-2,3-dihydro-1-benzofuran-3-yl]methyl 2-O-α-L-rhamnopyranosyl-β-D-glucopyranoside ( 2 ), [(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-2,3-dihydro-1-benzofuran-3-yl]methyl 2-O-α-L-rhamnopyranosyl-β-D-xylopyranoside ( 3 ), 3-[(2R,3S)-3-({[2-O-(4-O-acetyl-α-L-rhamnopyranosyl)-β-D-xylopyranosyl]oxy}methyl)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-2,3-dihydro-1-benzofuran-5-yl]propyl acetate ( 4 ), and 4-(2-hydroxyethyl)phenyl 3-O-β-D-glucopyranosyl-β-D-glucopyranoside ( 9 ). Free radical scavenging activities of the isolates were elucidated through the DPPH assay method. The most active compounds, 1-O-caffeoyl-β-D-glucopyranose ( 17 ) and soulieana acid 1 ( 18 ), exhibited moderate radical scavenging activities (IC₅₀=37.7±4.4 μM and IC₅₀=97.2±3.4 μM, respectively). The antibacterial activities of the isolates against Staphylococcus aureus and Escherichia coli were also assessed, and no activity was shown at the measured concentration (<32 μg/mL).     

Two new benzofuran derivatives from the fungus Stereum sp. YMF1.1684

A basidiomycete fungus, Stereum sp. YMF1.1684, was studied for its ability to produce new compounds on nutrient-enriched cultivation media. One new benzofuran, 2-hydroxy-1-((S)-2-(prop-1-en-2-yl)-2,3-dihydrobenzofuran-5-yl)propan-1-one, named as phenostereum A (1) and one novel dimer benzofuran, named as phenostereum B (2) were isolated from EtOAc extract of the culture broth of the fungus Stereum sp. YMF1.1684. The structures were elucidated using spectroscopic data from 1D, 2D NMR and HRESIMS experiments.     

Development of selective inhibitors for the treatment of rheumatoid arthritis: (R)-3-(3-(Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile as a JAK1-selective inhibitor

A series of 3(R)-aminopyrrolidine derivatives were designed and synthesized for JAK1-selective inhibitors through the modification of tofacitinib’s core structure, (3R,4R)-3-amino-4-methylpiperidine. From the new core structures, we selected (R)-N-methyl-N-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine as a scaffold for further SAR studies. From biochemical enzyme assays and liver microsomal stability tests, (R)-3-(3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile (6) was chosen for further in vivo test through oral administration. Compound 6 showed improved selectivity for JAK1 compared to that of tofacitinib (IC₅₀ 11, 2.4?×?10², 2.8?×?10³, and 1.1?×?10²?nM for JAK1, JAK2, JAK3, and TYK2, respectively). In CIA and AIA model tests, compound 6 exhibited similar efficacy to tofacitinib citrate.     

Synthesis of pro-apoptotic indapamide derivatives as anticancer agents

Abstract

4-Chloro-3-({[(substitutedamino)carbonothioyl]amino}sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamide (1–20) and 4-chloro-3-({[3-(substituted)-4-oxo-1,3-thiazolidine-2-ylidene]amino}sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamide derivatives (21–31) were synthesized from 4-chloro-N-(2-methyl-2,3-dihydroindol-1-yl)-3-sulfamoylbenzamide (indapamide). 4-Chloro-3-({[(4-chlorophenyl) amino) carbonothioyl]amino}sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamide 12 demonstrated the highest proapoptotic activity among all synthesized compounds on melanoma cell lines MDA–MB-435 with 3.7% growth inhibition at the concentration of 10?µM. Compound 12 (SGK 266) was evaluated in vitro using the MTT colorimetric method against melanoma cancer cell line MDA–MB435 growth inhibition for different doses and exhibited anticancer activity with IC₅₀ values of 85–95?µM against melanoma cancer cell line MDA–MB435. In addition, this compound was investigated as inhibitors of four physiologically relevant human carbonic anhydrase isoforms, hCA I, II, IX and XII. The compund inhibited these enzymes with IC₅₀ values ranging between 0.72 and 1.60?µM.     

α-Glucosidase Inhibition by Usnic Acid Derivatives

This study investigated a set of new potential antidiabetes agents. Derivatives of usnic acid were designed and synthesized. These analogs and nineteen benzylidene analogs from a previous study were evaluated for enzyme inhibition of α-glucosidase. Analogs synthesized using the Dakin oxidative method displayed stronger activity than the pristine usnic acid (IC₅₀>200 μM). Methyl (2E,3R)-7-acetyl-4,6-dihydroxy-2-(2-methoxy-2-oxoethylidene)-3,5-dimethyl-2,3-dihydro-1-benzofuran-3-carboxylate ( 6b ) and 1,1′-(2,4,6-trihydroxy-5-methyl-1,3-phenylene)di(ethan-1-one) ( 6e ) were more potent than an acarbose positive control (IC₅₀ 93.6±0.49 μM), with IC₅₀ values of 42.6±1.30 and 90.8±0.32 μM, respectively. Most of the compounds synthesized from the benzylidene series displayed promising activity. (9bR)-2,6-Bis[(2E)-3-(2-chlorophenyl)prop-2-enoyl]-3,7,9-trihydroxy-8,9b-dimethyldibenzo[b,d]furan-1(9bH)-one ( 1c ), (9bR)-3,7,9-trihydroxy-8,9b-dimethyl-2,6-bis[(2E)-3-phenylprop-2-enoyl]dibenzo[b,d]furan-1(9bH)-one ( 1g ), (9bR)-2-acetyl-6-[(2E)-3-(2-chlorophenyl)prop-2-enoyl]-3,7,9-trihydroxy-8,9b-dimethyldibenzo[b,d]furan-1(9bH)-one ( 2d ), (9bR)-2-acetyl-6-[(2E)-3-(3-chlorophenyl)prop-2-enoyl]-3,7,9-trihydroxy-8,9b-dimethyldibenzo[b,d]furan-1(9bH)-one ( 2e ), (6bR)-8-acetyl-3-(4-chlorophenyl)-6,9-dihydroxy-5,6b-dimethyl-2,3-dihydro-1H-[1]benzofuro[2,3-f][1]benzopyran-1,7(6bH)-dione ( 3e ), (6bR)-8-acetyl-6,9-dihydroxy-5,6b-dimethyl-3-phenyl-2,3-dihydro-1H-[1]benzofuro[2,3-f][1]benzopyran-1,7(6bH)-dione ( 3h ), (6bR)-3-(2-chlorophenyl)-8-[(2E)-3-(2-chlorophenyl)prop-2-enoyl]-6,9-dihydroxy-5,6b-dimethyl-2,3-dihydro-1H-[1]benzofuro[2,3-f][1]benzopyran-1,7(6bH)-dione ( 4b ), and (9bR)-6-acetyl-3,7,9-trihydroxy-8,9b-dimethyl-2-[(2E)-3-phenylprop-2-enoyl]dibenzo[b,d]furan-1(9bH)-one ( 5c ) were the most potent α-glucosidase enzyme inhibitors, with IC₅₀ values of 7.0±0.24, 15.5±0.49, 7.5±0.92, 10.9±0.56, 1.5±0.62, 15.3±0.54, 19.0±1.00, and 12.3±0.53 μM, respectively.     

Novel antioxidant agents deriving from molecular combinations of vitamins C and E analogues: 3,4-dihydroxy-5(R)-[2(R,S)-(6-hydroxy-2,5,7,8-tetramethyl-chroman-2(R,S)-yl-methyl)-[1,3]dioxolan-4(S)-yl]-5H-furan-2-one and 3-O-octadecyl derivatives

Molecular combinations of two antioxidants (i.e., ascorbic acid and the pharmacophore of α-tocopherol), namely the 2,3-dihydroxy-2,3-enono-1,4-lactone and the chromane residues, have been designed and tested for their radical scavenging activities. When evaluated for their capability to inhibit malondialdehyde (MDA) production in rat liver microsomal membranes, the 3,4-dihydroxy-5R-2(R,S)-(6-hydroxy-2,5,7,8-tetramethylchroman-2(R,S)yl-methyl)-1,3]dioxolan-4S-yl]-5H-furan-2-one (11a–d), exhibited an interesting activity. In particular the 5R,2R,2R,4S and 5R,2R,2S,4S isomers (11c,d) displayed a potent antioxidant effect compared to the respective synthetic α-tocopherol analogue (5) and natural α-tocopherol or ascorbic acid, used alone or in combination. Moreover, the mixture of stereoisomers 11a–d also proved to be effective in preventing damage induced by reperfusion on isolated rabbit heart, in particular at the higher concentration of 300 μM. In view of these results our study represents a new approach to potential therapeutic agents for applications in pathological events in which a free radical damage is involved. Design, synthesis and preliminary biological activity are discussed.     

Bioenergetics of juvenile whitespotted bamboo shark Chiloscyllium plagiosum [Anonymous (Bennett)]

This study establishes the bioenergetics budget of juvenile whitespotted bamboo shark Chiloscyllium plagiosum by estimating the standard metabolic rate (R_S), measuring the effect of body size and temperature on the R_S, and identifying the specific dynamic action (R_SDA) magnitude and duration of that action in juvenile whitespotted bamboo sharks. The mean ±s .d . (R_S) of six fish (500–620 g) measured in a circular closed respirometry system was 30·21 ± 5·68 mg O₂ kg^?1 h^?1 at 18° C and 70·38 ± 14·81 mg O₂ kg^?1 h^?1 at 28° C, respectively. There were no significant differences in R_S between day and night at either 18 or 28° C (t‐test, P > 0·05). The mean ±s .d . Q₁₀ for 18–28° C was 2·32 ± 0·06 (n = 6). The amount of oxygen consumed per hour changed predictably with body mass (M; 295–750 g) following the relationship: (n = 40, r²= 0·92, P < 0·05). The mean magnitude of R_SDA was 95·28 ± 17·55 mg O₂ kg^?1 h^?1. The amount of gross ingested energy (E_I) expended as R_SDA ranged from 6·32 to 12·78% with a mean ±s .d . of 8·01 ± 0·03%. The duration of the R_SDA effect was 122 h. The energy content of juvenile whitespotted bamboo shark, squid and faeces determined by bomb calorimeter were 19·51, 20·3 and 18·62 kJ g dry mass^?1. A mean bioenergetic budget for juvenile whitespotted bamboo sharks fed with squid at 18° C was 100C = 29·5G + 31·9R_S+ 28·2R_SDA+ 6·7F + 2·1E + 1·6U, where C = consumption, G = growth, F = egestion, E = excretion and U = unaccounted energy.     

Moandaensine,a dimeric indole alkaloid from Strychnos moandaensis (Loganiaceae)

The chemical investigation of the liana Strychnos moandaensis De Wild. led to the isolation of moandaensine, a novel dimeric indole alkaloid. The structure was elucidated by a thorough analysis of the spectroscopic data and by molecular modeling. Moandaensine, or methyl (2S)-2-[(2R,3E,12bS)-3-ethylidene-2,4,6,7,12,12b-hexahydro-1H-indolo[2,3-a]quinolizin-2-yl]-3-[(2S,3R)-3-ethyl-2-[(1R)-1-(hydroxymethyl)-2-methoxy-2-oxo-ethyl]-1,2,3,4-tetrahydroindolo[2,3-a]quinolizin-5-ium-7-yl]propanoate, contains a rare anhydronium base subunit. It presents a moderate antiplasmodial activity with IC₅₀ values of 11.2 and 9.2 μM against, respectively, the chloroquine sensitive FCA 20 GHA and chloroquine resistant W2 strains of Plasmodium falciparum.     

The Synthesis of Enantiomerically Pure Pyrazolo[4,3-c]pyridine Carbarzbo C-Nucleoside

Abstract

The synthesis of (-)-3-[(1S,2S,3R,4R)-2,3-dihydroxy-4-(hydroxmethyl) cyclopentan-1-yl]-1H-pyrazolo[4,3-c]pyridme-4,6(5H,7H)-dione 3 was accomplished via enantiomerically pure carbocyclic 5-(β-D-ribofuranosyl)tetrazole 4.     

Production of (R )-3-pentyn-2-ol through stereospecific hydrolysis of racemic 3-pentyn-2-ol esters with microbial enzymes

Microorganisms and commercial enzymes were screened for their ability to produce (R)-3-pentyn-2-ol from racemic 3-pentyn-2-ol esters through stereospecific hydrolysis. Among the esters formed with acetic acid, propionic acid, hexanoic acid and benzoic acid, the acetate was most effectively hydrolyzed by microbial cells and commercial lipases with high stereospecificity. Rhodococcus rubropertinctus AKU NOC082 was a good catalyst for (R)-3-pentyn-2-ol production through the hydrolytic resolution of racemic 3-pentyn-2-yl acetate. With 15%, 25% and 50% (v/v) racemic 3-pentyn-2-yl acetate as the substrate, 42.6%, 40.8% and 40.0% was hydrolyzed in 5 h, 10 h and 98 h respectively, under the optimized conditions (pH 7.0, 30 °C, 7.5% wet cell concentration), the (R) enantiomer of 3-pentyn-2-ol being formed with an optical purity of 97.8%, 98.0% and 94.2% respectively. Received: 2 June 1998 / Received revision: 3 August 1998 / Accepted: 3 September 1998     

Aerobic scope for activity in age 0 year Atlantic cod Gadus morhua

Key components of swimming metabolism: standard metabolism (R_s), active metabolism (R_a) and absolute aerobic scope for activity (R_a–R_s) were determined for small age 0 year Atlantic cod Gadus morhua. Gadus morhua juveniles grew from 0·50 to 2·89 g wet body mass (M_WB) over the experimental period of 100 days, and growth rates (G) ranged from 1·4 to 2·9% day^?1, which decreased with increasing size. Metabolic rates were recorded by measuring changes in oxygen consumption over time at different activity levels using modified Brett‐type respirometers designed to accommodate the small size and short swimming endurance of small fishes. Power performance relationships were established between oxygen consumption and swimming speed measurements were repeated for individual fish as each fish grew. Mass‐specific standard metabolic rates () were calculated from the power performance relationships by extrapolating to zero swimming speed and decreased from 7·00 to 5·77 μmol O₂ g^?1 h^?1, mass‐specific active metabolic rates () were calculated from extrapolation to maximum swimming speed (U_max) and decreased from 26·18 to 14·35 μmol O₂ g^?1 h^?1 and mass‐specific absolute scope for activity was calculated as the difference between active and standard metabolism () and decreased from 26·18 to 14·35 μmol O₂ g^?1 h^?1 as M_WB increased. Small fish with low R_s had bigger aerobic scopes but, as expected, R_s was higher in smaller fish than larger fish. The measurements and results from this study are unique as R_s, R_a and absolute aerobic scopes have not been previously determined for small age 0 year G. morhua.     

Effect of the structure of dietary epoxylignan on its cytotoxic activity: relationship between the structure and the activity of 7,7′-epoxylignan and the introduction of apoptosis by caspase 3/7

We compared the cytotoxic activities of dietary epoxylignans and their stereoisomers and found (?)-verrucosin, which is (7S,7′R,8R,8′R)-7,7′-epoxylignan, to be the most cytotoxic epoxylignan against HeLa cells (IC₅₀ = 6.6 μM). On the other hand, the activity was about a factor of 10 less against HL-60. In this research on the relationship between the structure and cytotoxic activity of (?)-verrucosin 13, the 7-(4-methoxyphenyl)-7′-(3,4-dimethoxyphenyl) derivative 60, for which the activity (IC₅₀ = 2.4 μM) is three times greater than (?)-verrucosin 13, was discovered. The induction of apoptosis by caspase 3/7 was observed upon treatment with the (?)-verrucosin derivative.     

Synthesis,Biological Evaluation and in Silico Studies of 3-Hydroxy-N-(2-(substituted phenyl)-4-oxothiazolidin-3-yl)-2-napthamide Derivatives

In the present study, a series of 3-hydroxy-N-(2-(substituted phenyl)-4-oxothiazolidin-3-yl)-2-napthamide derivatives were synthesized, characterized and evaluated for theirin vitroactivity, i. e., antimicrobial, antioxidant and anti-inflammatory. The target compounds were synthesized by condensation reaction of 3-hydroxy-2-naphthoic acid hydrazide with substituted benzaldehydes which were subjected to cyclization reaction with thioglycolic acid and ZnCl₂ to get target compounds. The synthesized 3-hydroxy-N-(2-(substituted phenyl)-4-oxothiazolidin-3-yl)-2-napthamide derivatives were examined for their antimicrobial activity and 3-hydroxy-N-(4-oxo-2-(3,4,5-trimethoxyphenyl)thiazolidin-3-yl)-2-naphthamide ( S20 ) exhibited the highest antimicrobial potential. The N′-(2,3-dichlorobenzylidene)-3-hydroxy-2-naphthohydrazide ( S5 ) displayed good antifungal potential against Rhizopus oryzae, whereas N′-(2,3-dichlorobenzylidene)-3-hydroxy-2-naphthohydrazide ( S20 ) showed the highest antioxidant potential and N-(2-(2,6-dichlorophenyl)-4-oxothiazolidin-3-yl)-3-hydroxy-2-naphthamide ( S16 ) displayed the highest anti-inflammatory activity. The results of molecular docking studies revealed that existence of hydrogen bonding and hydrophobic interactions with their respective proteins. In silico ADMET studies were carried out by Molinspiration, Pre-ADMET and OSIRIS property explorer to predict the pharmacokinetic behaviour of synthesized 3-hydroxy-N-(2-(substituted phenyl)-4-oxothiazolidin-3-yl)-2-napthamide derivatives.     

Synthesis of Imidazole-2,3-dihydrothiazole Compounds as VEGFR-2 Inhibitors and Their Support with in Silico Studies

In this study, 12 novel 2-((1-(4-(1H-imidazol-1-yl)phenyl)ethylidene)hydrazineylidene)-3-ethyl-4-(substitutephenyl)-2,3-dihydrothiazole derivatives were obtained. Among these compounds, 2-((1-(4-(1H-imidazol-1-yl)phenyl)ethylidene)hydrazineylidene)-4-([1,1′-biphenyl]-4-yl)-3-ethyl-2,3-dihydrothiazole ( 4h ) was chosen as the most active derivative in the series. According to the MTT results, compounds 4h and 4k showed activity with IC₅₀=4.566±0.246 μM and IC₅₀=4.537±0.463 μM, respectively. Unlike other derivatives, compound 4h carries a phenyl ring in the 4th position of the phenyl ring. This bulky group allowed the compound to settle in the enzyme active site. Dynamic studies show that the stability of the compound does not change over 40 ns. RMSD, RMSF and Rg parameters all remained within acceptable limits. The uninterrupted aromatic hydrogen bonding of the enzyme active site with the important amino acids Cys919, Glu885 and Asp1046 proves the inhibitory potential of compound 4h on the VEGFR-2 enzyme. It is thought that more active compounds will be reached with the derivatives to be synthesized starting from compound 4h .     

Ferulic acid dehydrodimers from wheat bran: isolation,purification and antioxidant properties of 8-0-4-diferulic acid

Summary

Wheat bran contains several ester-linked dehydrodimers of ferulic acid, which were detected and quantified after sequential alkaline hydrolysis. The major dimers released were: trans-5-[(E)-2-carboxyvinyl]-2-(4-hydroxy-3-methoxy-phenyl)-7-methoxy-2,3-dihydrobenzofuran-3-carboxylic acid (5–8-BendiFA), (Z)-β-(4-[(E)-2-carboxyvinyl]-2-methoxy-phenoxy)-4-hydroxy-3-methoxycinnamic acid (8-O-4-diFA) and (E,E)-4,4′-dihydroxy-5,5′-dimethoxy-3,3′-bicinnamic acid (5–5-diFA). trans-7-hydroxy-1-(4-hydroxy-3methoxyphenyl)-6-methoxy-1,2-dihydro-naphthalene-2,3-dicarboxylic acid (8–8-diFA cyclic form) and 4,4′-dihydroxy-3,3′-dimethoxy-β,β'-bicinnamic acid (8–8-diFA non cyclic form) were not detected. One of the most abundant dimers, 8-O-4-diFA, was purified from de-starched wheat bran after alkaline hydrolysis and preparative HPLC. The resultant product was identical to the chemically synthesised 8-O-4-dimer by TLC and HPLC as confirmed by ¹H-NMR and mass spectrometry. The absorption maxima and absorption coefficients for the synthetic compound in ethanol were: λ_max: 323 nm, λ_min: 258 nm, ε_λmax (M^?1cm^?1): 24800 ± 2100 and ε₂₈₀ (M^?1cm^?1): 19700 ± 1100. The antioxidant properties of 8-O-4-diFA were assessed using: (a) inhibition of ascorbate/iron-induced peroxidation of phosphatidylcholine liposomes and; (b) scavenging of the radical cation of 2,2′-azinobis (3-ethyl-benzothiazoline-6-sulphonate) (ABTS) relative to the water-soluble vitamin E analogue, Trolox C. The 8-O-4-diFA was a better antioxidant than ferulic acid in both lipid and aqueous phases. This is the first report of the antioxidant activity of a natural diferulate obtained from a plant.     

Anticancer evaluation and molecular modeling of multi-targeted kinase inhibitors based pyrido[2,3-d]pyrimidine scaffold

An efficient synthesis of substituted pyrido[2,3-d]pyrimidines was carried out and evaluated for in vitro anticancer activity against five cancer cell lines, namely hepatic cancer (HepG-2), prostate cancer (PC-3), colon cancer (HCT-116), breast cancer (MCF-7), and lung cancer (A-549) cell lines. Regarding HepG-2, PC-3, HCT-116 cancer cell lines, 7-(4-chlorophenyl)-2-(3-methyl-5-oxo-2,3-dihydro-1H-pyrazol-1-yl)-5-(p-tolyl)- pyrido[2,3-d]pyrimidin-4(3H)-one (5a) exhibited strong, more potent anticancer (IC₅₀: 0.3, 6.6 and 7?µM) relative to the standard doxorubicin (IC₅₀: 0.6, 6.8 and 12.8?µM), respectively. Kinase inhibitory assessment of 5a showed promising inhibitory activity against three kinases namely PDGFR β, EGFR, and CDK4/cyclin D1 at two concentrations 50 and 100?µM in single measurements. Further, a molecular docking study for compound 5a was performed to verify the binding mode towards the EGFR and CDK4/cyclin D1 kinases.     

Asymmetric synthesis and effect of absolute stereochemistry of YCZ-2013, a brassinosteroid biosynthesis inhibitor

The four stereoisomers of 2RS,4RS-1-[[2-(2,4-dichlorophenyl)-4-(2-(2-propenyloxy)phenoxymethyl)-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole (YCZ-2013), a novel brassinosteroid biosynthesis inhibitor, were prepared. The diastereomers of 2RS,4R-5 and 2RS,4S-5 were prepared by using the corresponding optically pure R and S toluene-4-sulfonic acid 2,3-dihydroxypropyl ester (R-4,S-4). The enatiomerically and diastereomerically pure acetonide (5) was obtained by a method involving diastereoselective crystallisation of the tosylate salt, followed by re-equilibration with the mother liquor and chromatography. The optical purity of four target compounds (YCZ-2013) was confirmed by chiral high-performance liquid chromatography (HPLC) and NMR. The effects of these stereoisomers on Arabidopsis stem elongation indicated that the cis isomers of 2S,4R-YCZ-2013 and 2R,4S-YCZ-2013 exhibited potent inhibitory activity with IC₅₀ values of approximately 24 ± 3 and 24 ± 2 nM, respectively. The IC₅₀ values of the trans isomers of 2S,4S-YCZ-2013 and 2R,4R-YCZ-2013 are approximately 1510 ± 50 and 3900 ± 332 nM, respectively. Co-application of brassinolide (10 nM), the most potent BR, and GA₃ (1 μM) to Arabidopsis seedlings grown in the dark with 2R,4S-YCZ-2013 and 2S,4R-YCZ-2013 revealed that brassinolide recovered the induced dwarfism of Arabidopsis seedlings, whereas GA₃ showed no effect.     

Reproductive biology of female bigeye tuna Thunnus obesus in the western Pacific Ocean

The reproductive biology of female bigeye tuna Thunnus obesus was assessed by examining 888 fish (ranging from 84·9 to 174·4 cm fork length, L_F) caught by Taiwanese offshore longliners in the western Pacific Ocean from November 1997 to November 1998 and November to December 1999 and 258 gonad samples from these fish. The overall sex ratio of the catch during the sampling differed significantly from 0·5, but males were predominant in sizes >140 cm L_F. Reproductive activity (assessed by histology), a gonado‐somatic index, and the size‐frequency distributions of whole oocytes indicated that spawning occurred throughout the year and the major spawning season appeared to be from February to September. The estimated sizes at 50% maturity (L_F50) of females was 102·85 cm (95% c.i .: 90·79–110·21 cm) and the smallest mature female was 99·7 cm L_F. They are multiple spawners and oocytes develop asynchronously. The proportion of mature (0·63) and reproductively active (0·70) females with ovaries containing postovulatory follicles indicated that they spawn almost daily. Batch fecundity for 15 females with the most advanced oocytes (>730 µm) ranged from 0·84 to 8·56 million eggs (mean ± s.d . = 3·06 ± 2·09). The relationships between batch fecundity (F_B, in millions of eggs) and L_F (cm) and round mass (M_R, kg) were (r² = 0·84) and (r² = 0·80), respectively. The parameters estimated in this study are key information for stock assessments of T. obesus in the western Pacific Ocean and will contribute to the conservation and sustainable yield of this species.     

Optical resolution by preferential crystallization of (2RS,3SR)-2-amino-3-chlorobutanoic acid hydrochloride

(2RS,3SR)-2-Amino-3-chlorobutanoic acid hydrochloride [(2RS,3SR)-ACB · HCl] was found to exist as a conglomerate based on the melting point, infrared spectrum, and solubility. Optical resolution by preferential crystallization of (2RS,3SR)-ACB · HCl was achieved to yield both (2R,3S)- and (2S,3R)-ACB · HCl of 80–100% optical purities. The obtained (2R,3S)- and (2S,3R)-ACB · HCl were recrystallized, taking into account the solubility of (2RS,3SR)-ACB · HCl, to give efficiently optically pure (2R,3S)- and (2S,3R)-ACB · HCl. Treatment of the purified (2R,3S)- and (2S,3R)-ACB · HCl with triethylamine gave optically pure (2R,3S)- and (2S,3R)-2-amino-3-chlorobutanoic acid, respectively. Chirality 9:656–660, 1997. © 1997 Wiley-Liss, Inc.     

Syntheses of all eight stereoisomers of conidendrin

ABSTRACT

All eight stereoisomers of conidendrin were synthesized from (1 R,2 S,3 S)-1-(4-benzyloxy-3-methoxyphenyl)-3-(4-benzyloxy-3-methoxybenzyl)-2- hydroxymethyl-1,4-butanediol ((+)-4) and its enantiomer with high optical purity. The configurations at 4-positions of the conidendrin stereoisomers were constructed by intramolecular Friedel-Crafts reaction of protected 4. After conversion to tetrahydronaphthalene intermediate 7a, the 2- and 3-position of tetrahydronaphthalene structure 7a were converted to 3a- and 9a-position of (+)-α-conidendrin (3a), respectively. By the epimerization process of 2- or 3-position of 7a, the other diastereomers were obtained. All enantiomers were also synthesized from (?)-4.