Callipeltin A (1) is a cyclodepsipeptide from water sponge collected at New Caledonia. This compound shows anti-HIV and cytotoxic activities against KB and P388 cells and contains three new amino acid residues. β-methoxytyrosine (β-MeOTyr) (), (2R,R,S)--amino--guanidino-2,--dihydroxyheptanoic acid (AGDHE) (5), (S,R)-,-dimethyl-L-glutamine (diMeGln) (6). In addition, two new truncated open-chain derivatives of Callipeltin A (1), named Callipeltin D (2) and () were isolated. The unique structure and intriguing biological activities of this compound led us to explore total synthesis of Callipeltin A (1) and to elucidate stereochemistry of β-MeOTyr (). We started to synthesize Callipeltin () which contains β-MeOTyr (). In order to synthesize four stereoisomer of β-MeOTyr (), we attempted Evans anti or syn-Aldol reaction as a key step. Evans direct anti-aldol reaction with chiral benzyloxazolidinones () and p-hydroxy benzaldehyde () promoted by catalytic amounts of MgCl_2 in the presence of triethylamine and chlorotrimethylsilane. This proceder provide :1 diastereoselelctivity and 70% yield of isolated anti-aldol product (10). And Enolizalion of isocyanate oxazolidinone (13) with di-n-butylboryl trifrate and diisopropylethylamine followed by treatment with aldehyde afford syn-aldol product 14 affording 88% yield and 1:5 anti: sin diastereomeric ratio. On the other hand, we tried Sharpless Asymmetric dihydroxylation () and Aminohydroxylation () to give all four stereoisomers of β-MeOTyr. Treatment of olefin (18) with -mix α provided diol (19) and the α position alcohol of 19 was converted to sulfone regioselectively followed by azidation and treatment of 20 with PPh_ to afford aziridine (21). Addition of aziridine (21) and _・Et_2O in methanol produced α-amino β-methoxy adduct (). reaction protocol with t-butylcarbamate was successfully applied to afford desired in single step. Now we construct Callipeltin to determine absolute stereochemistry of β-MeOTyr (). In addition, we report the synthesis of diMeGln (6) and (2R,R,S)--hydroxy-2--6-trimethyl hepanoic acid ().

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[1] The purpose of this reserch is to make clear what type of design can give good effects to win the high readership score. At the begining I had to know what factors decide the readership score, and how to change the quality of the desing into numerical value. I have used the method of multi-dimentional analysis with the help of a computer, and got the estimation formula, with kinds of factors, as follows ; A^^〜=B+C+D+K+aE++cG. A^^〜=estimated values of the readership score. 1) B, C, D, K : these four factors are given as category values (so we call them); each factor is classified into several categories. B=week day, classified into categories. C=pages of a newspaper, which are characterized by the kinds of articles, news, and the other reading matters, classified into categories. D=kinds of goods and trades of the advertizement, classified into 14 catedories. K=constants, given to each 13 surveys. 2) , , G : these factors are given as numerical values. G=area of advertizement, measured by the unit of column in the whole page length, being classified into 6 kinds of area (2.5, .5, 5, , 10, 15) and 15 column means a whole page, about 2,000cm^2. , are the marks obtained in the design of advertizements. =sum of the marks obtained in each design element on the advertizement. =the marks obtained on the whole effect of the design. ) a, b, c : coefficients Using the above formula with the category values and the coefficients, we can obtain the naked design effect from the actual value A of readership score: aE+=A-(B+C+D+K+cG). In this research, I used 1,829 data of readership score from 1960 to 1968, being obtained by 13 survevs, spring and autumn twice a year. The sample of size each survey was ,541, 2,251, or 200 in the other 11 surveys. Multiple correlation coefficient between the estimated value A^^〜 and the actual value A is 0.951. The table 2^* shows the contribution indexes of each factor by kinds of expression-(1) Range : the absolute difference between the maximum and the minimum category values, (2) Standard deviations of the category values, () Partial correlation coefficient : the relationship between the actual values A and each factors. *see the table 2 in the thesis in Japanese. [2] The important point was in the determination of the values of , . is the sum of the marks obtained in each design element, classified into four kinds : =_1+_2+_+_. design elements [table] _1, _2, _, _, these values have the 5 grades, as 0, 1, 2, , and 0 is given to the design that has no attractive effect or no applicable element. And obtain the marks of 0 to grades as the sum of them. The values of have also 5 grades, 0 to . The principles to determine the values of , are as follows : a) The marks obtained of , must be the relative values among the each survey, and at the same time, they must have constancy within the same survey-the same elements of design must win the same marks obtained. b) They must be determined as to win the highest multiple correlation coefficient, when they are put into the estimation formula. c) They must be reasonable. In order to justify them, we must carry many researches on the actual condition. The frequency of accurence of each grade of , values, as the table 5-, and 5-5 in the thesis in Japanese.

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Four new sterols, 5α, 6α-epoxy-(, 24R)-ergosta-(14), -diene-, -diol (1), (, 24R)-ergosta-, -diene-, 5α, 6β, -tetrol (2), (, 24R)-ergosta-, (11), -triene-, 5α, 6β-triol () and , 5α, 6β-trihydroxy-(, 24R)-ergost--en--one (), have been isolated from the fruit bodies of Grifola frondosa (FR.) S. . GRAY (Polyporaceae)together with fourteen known ones (5-18), of which two (5 and 6) are reported for the first time from a natural source. The structures of these compounds were elucidated on the basis of spectral data.

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Six new cembranoids sarcophytol P (), R (), S (5), K (), (11), and T (13) were isolated from the soft coral Sarcophyton glaucum. Sarcophytol P () was shown to be the 20-hydroxy derivative of the major component sarcophytol A (1), and afforded the cyclization product 6 in CHCl_ at room temperature, in a same way as in 1. Sarcophytols R () and S (5) were correlated to 1, by conversion of its R,R and S,S epoxide derivatives. Sarcophytol K() was a 13, 14-dihydroxycembranoid having a 1,Z-diene moiety. The absolute configuration of and its 1Z,- and 1Z,Z-isomers sarcophytol B (2) and J (10) were determined by circular dichroism study of their bis-p-dimethylaminobenzoate derivatives. Sarcophytols (11) and T (13) were 1- and 1,Z-isomers of 1. Compound 11 showed characteristic broadening of the ^1H-NMR chemical shifts, due to the restricted conformational interconversion. Using the three cembranoids sarcophytols (11, 1,), N (15, 1Z,Z) and T (13,1,Z), spontaneous autoxidation-cyclization, in CHCl_,was examined, in order to compare the stereochemical course of the reaction with that of 1 (1Z,), which affords trans-fused bicyclo[..0]tetradecene systems. The 1,Z-isomer 13 gave the same cyclization product 18, as in the reaction of 1, even though it is isomeric at C-1,. The 1Z,Z isomer 15 gave 19, in consequence of the reversed geometry at C- of 15. The 1,-isomer (11) gave the bicyclic product , having an antipodal fusion as compared with 19. This was confirmed by PCC oxidation of 19 and , giving enantiomeric ketones 23 and 24 respectively. The 1(14)-epoxide 26 was shown to be the immediate precursor of , and acounted for the inversion of the geometry at C-1 of the cyclization product. Compound 26 is isomeric with the epoxide 17 derived from 1. The epoxide 17 is the postulated precursor in the conversion of 13 to 18. It is noteworthy that the mode of antipodal fusion of the cyclopentane rings, in 18 and , was controlled by the chirality of the epoxy rings. The C-14 hydroxyl group participates in the transannular cyclization, but was found not to be the requisite functional group for the reaction. Similar treatment of cembrene C (30), the parent hydrocarbon of 1, also reacted in CHCl_ giving the bicyclic product 32.

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We screened the differentiation-inducing activities of 39 mushroom extracts from Akita prefecture, Japan, on the mouse osteoblastic cell line, MCT-1. Sixteen phosphate buffered saline (PBS), boiled PBS, 14 ethanol and 12 methanol extracts induced alkaline phosphatase (ALP) activities, an indicator of MCT-1 cell differentiation. The enzyme activities were markedly induced by extracts of Tricholoma auratum, and we isolated the active compound from methanol extracts of this mushroom. Physical data for the isolated active compound were identical to those for (,24R)-ergosta-,-diene-,5α,6β-triol (1). 1 induced ALP activities of MCT-1 cells and promoted cell proliferation. To investigate the relationships between the chemical structure and differentiation-inducing activity of the compound, ALP-inducing activities of MCT-1 cells by 1, ergosterol (2), ergocalciferol (), cholesta-,5α,6β-triol (), -dehydrocholesterol (5) and cholecalciferol (6) were tested. The enzyme activities of MCT-1 cells were increased .0-fold by 10 μM 1 and 2.-fold by 10 μM . However, 2, , 5 and 6 did not induce MCT-1 cell ALP activity at 0.1—10 μM. These results suggested that the OH groups at C-5 and/or C-6 of 1 and played an important role in their differentiation-inducing activities on MCT-1 cells. Furthermore, 1 suppressed induction of MCT-1 cell apoptosis by serum starvation.

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Stress wave theory is applied to open-ended pipe piles to clarify the effects of soil plug on the behaviour of piles during driving and static loading. Measured field data and various numerical models are reviewed ; methods are presented to calculate wave propagation in both the pile and the soil plug ; modelling is presented which takes into account the interaction between the soil plug and the pile ; also presented is simplified method to estimate the loadsettlement relation of the pipe pile in static loading. By correlating observed and calculated values in two analytical cases, the authors demonstrate that incorporation of the soil plug (modelled as a series of masses and springs) is required to correctly predict pile behaviour during driving and static loading.

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A long term follow-up of patients after antero-lateral partial vertebrectomies (ALPV) was performed using patient charts and questionnaires. During the past 15 years, ALPV has been performed on 159 patients with cervical spinal disorders. Among them, 136 patients whose survey was performed more than 1 year ago were selected. 92 were male and 44 were female. Their ages ranged from 41 to , and the average age was 63.1. The follow-up period was from 1 to 14 years (the average being . years). Pathology included spondylosis 119, OPLL 31, canal stenosis and combined lesion cases. Surgical resuts were evaluated using a 5 grade scale (excellent ; , good ; G, fair ; , poor ; P and dead ; D). At discharge, group was 40.2%, G was 51.5%, was .2%, P was 0%, D was 0.%. At the end of the follow-up period was 36.%, G was 35.%, was 20.2%, P was .1% and dead was .%. None of the deaths were related to the surgery. However, the score obtained from the Neurosurgical Cervical Spinal Scale were essentially consistent. Results of the questionnaire showed that 61.% of the patients were satisfied, 30.1% were fairly satisfied and only .% were dissatisfied. Dissatisfied cases included 2 cases of surgical failure but most of them were related to the progressive worsening of other lesions such as thoracic, lumbar spinal lesions or peripheral neuropathy. In 2 cases reoperation was performed, one anterior fusion with fibular strut graft for kyphoscoliosis and the other anterior fusion with a mini-plate for a fracture of the lamina and slippage of the vertebral body. In some cases, weakness of the C5 root area was encountered but most of these were resolved in a few months. Radiologically, the bony defects of the vertebral body were observed to become smaller, namely they were replaced by new growth of bone slowly in all cases. Thus, ALPV seems to be a useful surgical procedure for multilevel cervical spinal disorders.

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Chemical properties of ergosta-, 6, (14), -tetraen--one (1) were investigated. Though 1 is rather stable to acids or bases, it reacts easily with two moleculres of oxygen on irradiation with UV light to give 6α, -epidioxy-14α-hydroperoxyergosta-, , -trien--one (2), which is transformed successively to 6α, ;, -diepoxy-14α-hydroperoxyergosta-, -dien--one () and 14α-hydroperoxy--hydroxyergosta-, , -triene-, 6-dione () under these reaction conditions.

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Eight new sterols, 5α, -epidioxy-(, 24R)-23-methylergosta-6, -dien--ol (1), , 5α, -trihydroxy-(, 24R)-23-methylergosta-, -dien-6-one (2), , 5α, -trihydroxy-(24S)-ergost--en-6-one (), , 5α, , 14α-tetrahydroxy-(, 24R)-ergosta-, -dien-6-one (), (, 24R)-ergosta-, -diene-, 5α, 6α, -tetrol (5), 5α, -epidioxy--hydroxy-(, 24R)-ergosta-, -dien-6-one (6), 5α, -epidioxy--hydroxy-(24S)-ergost--en-6-one () and 5α, 6α-epoxy-(, 24R)-ergosta-, -diene-, , 14α-triol (), have been isolated from five edible mushrooms, Lentinus edodes, Flammulina velutipes, Hypsizigus marmoreus, Pleurotus ostreatus and Pholiota nameko together with fifteen known ones (-23), of which two (16 and 17) are reported for the first time from a fungal source. The structures of these new compounds were elucidated on the basis of their spectral data.

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From the black coral Antipathies dichotoma, a sphingolipid (2S*,*,,)-2N-[tetradecanoyl]-(),()-icosadiene-1,-diol (1) and a steroid ()-methylcholesta-5,-diene-1α,,-triol (2) were isolated. Other known compounds, ,-dihydroxy-cholest-5-ene (), (,24S),5α,-epidioxy-24-methylcholesta-6,-dien--ol () and (,24S),5α,-epidioxy-24-methylcholesta-6,(11),-trien--ol (5). The structures were established on the basis of NMR spectroscopic analysis and comparison with literature. The antibacterial activity of five compounds was evaluated.

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Nagilactone (1), one of the simplest member of the biologically active nor-diterpenoid dilactones of Podocarpus nagi, was first synthesized from (+)-[S]-podocarpic acid (2). Ozonolysis of a 14-isopropyl-enone 10, derived from (+)-podocarpic acid in several steps, gave a keto-acid 12. The acid 12 was transformed into epimeric (at C-14) enolides, and 23, via reductive lactonization and subsequent dehydrogenation. The two enolides gave the same diene-acid 24 on treatment with KOtBu in DMSO. Stereospecific lactonization of 24 to 14α-isopropyl-:-enolide 25 was achieved photochemically under irradiation in ethanol solution. On dehydrogenation with DDQ/_:ether in refluxing dioxane, 25 gave a dienolide 27, which equipped with suitable functional groups and stereochemistry on the ring C necessary for nagilactone . The dienolide ester 27 was hydrolyzed with conc. H_2SO_ to form a dienolide acid 28, which was successfully changed to nagilactone by Pb(OAc)_ oxidation. Reductive degradation of nagilactone to the synthetic intermediates, 28, 25 and 24, was also done, starting from nagilactone , a typical natural dilactone of P. nagi.

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Six new sterols, 5α, 6α;, -diepoxy-(, 24R)-ergost--ene-, -diol (1), 5α, 6α;, -diepoxy-(, 24R)-ergost--ene-, -diol (2), 5α, 6α-epoxy-(, 24R)-ergosta-, -diene-, -diol (), (, 24R)-23-methylergosta-, -diene-, 5α, 6β-triol (), (, 24R)-23-methulergosta-, -diene-, 5α, 6β, -tetrol (5) and (24S)-ergost--ene-, 5α, 6β, -tetrol (6), have been isolated from seven mushrooms, Amanita pantherina, Amantia virgineoides, Lactarius piperatus, Lyophyllum shimeji, Tricholoma portentosum, Hypsizigus marmoreus and Lentinula edodes together with eighteen known ones (-24). The structures of these new compounds were elucidated on the basis of their spectral data.

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In the first part of the present work the interaction of glycophorin with dimyristoylphosphatidylcholine (DMPC) is studied by freeze fracture electron microscopy, densitometry, calorimetry, and 90° static light scattering. An exothermic lipid/protein interaction energy of W_P=190 kJ•mol^-1 was found by application of the well known Van Laar relation for the displacement of the freezing point and the Gibbs-Duhem relationship. Secondly, the effects of Ca²⁺ on the lipid/protein interaction were studied. Following Ca²⁺ addition a remarkable decoupling of the interaction of the glycophorin head group with the bilayer surface was revealed by densitometry and gold-labeling electron microscopy. It is estimated that about 80% of lipid once disturbed by the adsorption of glycophorin head groups is decoupled after addition of Ca²⁺. Thirdly, the selective interaction of glycophorin with binary lipid mixtures was studied, including the mixtures of DMPC with dimyristoylphosphatidylserine (DMPS) and dilauroylphosphatidylcholine (DLPC), and the mixture of dipalmitoylphosphatidylcholine (DPPC) with DLPC.

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This study aimed to determine the prevalence of fecal carriage of extended spectrum β-lactamase (ESBL) and/or plasmidic AmpC β-lactamase (pAmpC) producing Escherichia coli among dogs (n=428) in Turkey. Polymerase chain reaction (PCR) and sequencing were used to characterize genes encoding β-lactamase and plasmid mediated quinolone resistance (PMQR). Antimicrobial susceptibility testing and PCRs for virulence genes and phylogenetic groups were also performed. Cefotaxime resistant

. coli isolates were detected in 95 (.2%) of the swab samples. Sequencing analysis results showed occurrence of various β-lactamase genes: bla_CTX-M-15 (62), bla_TEM-1b (42), bla_CMY-2 (), blaCTX-M-

3

(16), bla_CTX-M-1 (15), bla_OXA-1 (

9

) and bla_SHV-12 (

3

) alone or in combination. The most frequently encountered phylogenetic group was group A₁ (35.

8

%), followed by group D₂ (

22

.1%), B1 (15.

8

%), D₁ (

9

.5%), A₀ (

7

.

4

%),

B2₂

(5.

3

%) and B2₃ (

4

.2%), respectively. PMQR genes, aac(6’)-Ib-cr, qnrS1 and qnrB10 were detected in 25.

3

, 10.5 and 1.1% of the isolates, respectively. While all isolates were susceptible to imipenem and amikacin, resistance rates to non-β-lactam antibiotics ranged from 20.0% for tobramycin to 56.

8

% for tetracycline. The virulence genes were only detected in 34 (36.2%) of the isolates and this isolates carried single or various combination of virulence genes of iucD, papC, papE,

f17a

-A and eaeA. Four isolates were identified as human virulent pandemic CTX-M-15 producing

E

. coli clone O25b:ST131/B2. To the best of our knowledge, this is the first study to show fecal carriage of ESBL/pAmpC type β-lactamase producing

E

. coli isolates among dogs in Turkey.

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Chemical synthesis of (, 24R)- and (, 24S)-1, 24-dihydroxy--vitamin has been achieved starting with the commercially available dinorcholenic acid acetate. Synthesis involved introduction of the 1-hydroxy group by a reduction of the 1, 2-epoxide generated by epoxidation of the 1, , 6-trien--one. The side chain on the steroid was then constructed by means of a Wittig reaction followed by introduction of the bond by standard methods and its protection with 1-phenyl-1, 2, -triazoline-, 5-dione. Subsequent reduction of the hydroxy groups in the steroid side chain followed by reduction of the Diels-Alder addition products yielded the both 24-isomers. The 5, -dienes were irradiated and the corresponding vitamin D compounds isolated. Nuclear magnetic resonance was used to identify individual isomers. The (, 24S)-1, 24-hydroxyvitamin compound bound equally well to the chick intestinal cytosol receptor as 1, 25-dihydroxyvitamin , while the 24R-isomer was approximately ten times less active. In vivo, both isomers were less active than 1, 25-dihydroxyvitamin ; however, the 24S-isomer was considerably more active than the 24R-isomer approaching the activity of 1, 25-dihydroxyvitamin .

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Ten furostanol saponins were isolated as five pairs of 25R and 25S epimers from the fresh rhizomes of Polygonatum kingianum. Seven of them were identified as new compounds, (25S)-kingianoside D (2), (25S)-kingiano-side C (), (25R,)-hydroxylwattinoside C (5), kingianoside (), (25S)-kingianoside (), kingianoside () and (25S)-kingianoside (10), together with three known saponins, kingianoside C (1), kingianoside D (), and -hydroxylwattinoside C (6). The structures of the new saponins were determinded by detailed analysis of their 1D and 2D NMR spectra, and by comparison of the spectral data with those reported.

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