A sample of [³H] tobrarnycin (, 000 Ci/Mole) has been synthetized and incubated with
the bacterial ribosome and its subunits. The results obtained show that this antibiotic has
two types of binding sites. The primary one is probably responsible for the inhibition of
protein synthesis whereas the secondary one is probably related to the misreading and reading
tiirough of the messenger RNA.

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魚市場およびと畜場のドブネズミにおけるStaphylococcus auresの保有率はそれぞれ74.6% (44/59), 34.6% (/26) であった. 魚市場のネズミ由来S. aureus104株の生物型は型81株 (77.%), 型16株 (15.4%), A型6株 (.%), 型別不能1株 (1%) で, と畜場由来株はG型株 (88.%), 型1株 (11.1%) であった. 魚市場のネズミ由来株のコアグラーゼ型は, VIII型 (26.%), 1型 (.1%), VII型 (13.%), IV型 (.7%), II型 (.%), III型 (2.%), V型 (2.%), VI型 (2.%), 同定不能 (14.4%) で, と畜場由来株は, VIII型 (44.4%), V型 (.2%), VI [型 (.2%), 同定不能 (11.1%) であった.魚市場のネズミ匹由来の12株からはエンテロトキシンA (11株) および (1株) が産生された.

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Agaricus blazei is an important fungus for producing bioactive compounds. There are some reports of polysaccharides and steroid derivatives from the fruiting bodies of A. blazei. However, the chemical examination of the secondary metabolites of the cultured mycelia of this species has not been reported. Eight compounds, an unprecedented skeleton have been isolated from the cultured mycelia of A. blazei. The structures of the novel compounds each named blazeispirols A (1), (2), (3), D (4), () X(6), Y (7) and Z () were confirmed by extensive 1D and 2D NMR spectral data and X-ray analysis. Blazeispirols A (1), (2), (3), D (4) and () were des-A-ergostane type compounds having spiroacetal structure as a side chain. Blazeispirols X (6) and Y (7) were determined to be (20S, S, 23R, 24S)-1 (10→6) abeo-14β, :, 25-diepoxyergosta-,7,,11-tetraene-3α,23-diol and (20S, S, 23R, 24S)-14β,:,25-diepoxy-,23-dihydroxyergosta-4,7,11-triene-3,6-dione by comparison of extensive 1D and 2D NMR spectral data with that of blazeispirol A. The biosynthesis of blazeispirol A was investigated by feeding ^<13>-labeled acetates and methionine to the growing cultures of A. blazei. The labeling patterns of 1 derived from singly and doubly ^<13>-labeled acetates were consistent with that of ergosterol reported previously except for the A-ring and then ^<14>-labeled ergosterol was incorporated into blazeispirol A. Taking the structures of blazeispirols Z and D into consideration, it can be assumed that blazeispirol A is biosynthesized from ergosterol by the cleavage of -4, - and -1, -10 bonds on retro aldol condensation and Michael reaction via such as intermediate A as shown in Fig. 4. A large number of ergostane-type steroids have been isolated from many fungi. However, blazeispirol A is the first example of a naturally occurring des-A-ergostane-type steroid including a spiroacetal structure moiety as a side chain.

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Pironetin 1 (PA-48153) is a novel unsaturated δ-lactone derivative isolated from the fermentation broths of Streptomyces species which shows immunosuppressive and plant growth regulating activities. Several total syntheses of 1 have been reported to date, but we show here a novel approach to 1 via a convergent route using our chiral building block, (1S,S,6R)--hydroxybicyclo[4.1.0]heptan-2-one . We dissected pironetin at 6-7 and employed the coupling of the epoxide 16 with the dithiane 25, which would be derived from , as a key step. The THP ether of was methylated and the following reduction gave an inseparable mixture of four diastereomers . After etherification, removal of THP group afforded separable isomers a and in a ratio of 13 to 1. The desired major isomer a was oxidized to ketone 6. Oxidation of 6 via silyl enol ether with osmium tetroxide gave ketol 21 in quantitative yield. Reduction of cyclopropylketone moiety of 21 under Birch condition afforded a mixture of a and . The ketol moiety of a and was oxidatively cleaved with lead tetraacetate in benzene-methanol to give the single aldo-ester 23. Acetalization of 23 followed by reduction of ester group gave aldehyde 24. Introduction of 2-unit via Takai's protocol as -olefin formation followed by thioacetalization afforded the dithiane 25, as 7-14 unit of pironetin. Meanwhile, the epoxide 16 as 1-6 unit was prepared from known epoxy alcohol 3 in 6 steps. Coupling reaction of two units, the dithiane 25 and the the epoxide 16, successfully gave the product with the whole skeleton 26 in high yield. Mercuric ion assisted hydrolysis of the thioacetal 26 gave ketol 27. Selective reduction of β-hydroxyketone 27 by Mori's method afforded and-diol 28a predominantly (91: ). Finally, desilylation and oxidation with manganese dioxide afforded pironetin 1.

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We compared three groups of pregnant women: placebo with normotensive women, group A which included preeclamptics, and group which comprised preeclamptics who were supplemented their diets with vitamins and . MDA increased from 6. ± 2. (placebo) to .48 ± 1.2 (A) and .02 ± 1. nmol/gHb (). NO concentrations were enhanced from 19.3 ± 4.2 (P) to 23. ± 6.4 (A) and 24.1 ± .4 μmol/L (). GSH contents were decreased from 10.42 ± 2.81 (P) to .02 ± 2.92 (A) and .39 ± 1.02 μmol/g Hb (), whereas GSSG concentrations increased from 0.98 ± 0.28 (P) to 1.24 ± 0.29 (A) and 1.08 ± 0.12 μmol/g Hb (). SOD activity decreased 23% in A and 14% in ; GRx decreased 27% in A and .% in ; GPx decreased 12% in A and .6% in . Catalase activity, however, increased 27% in A and 29% in as compared to control. Thus, we conclude that the use of vitamins and should be considered for the control of certain important biochemical indices during the development of preeclampsia; however, further studies are needed to develop methods for the prevention of preeclampsia in women at high risk.

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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), blaTEM-

1b

(42), bla_CMY-2 (

22

), bla_CTX-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%),

B

1 (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 O25

b

:ST131/

B

2. 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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3,3,7,11-Tetramethyltricyclo[6.3.0.0^<2,4>]undecane skeleton is found in a number of natural products, which are divided into two groups, aromadendranes (I) and alloaromadendranes (II). Recently, some coupled compounds with other organic moieties were found, .g., macrocarpals (3), which were exhibiting HIV-RTase inhibitory activities. We planned to develop a general synthetic route to these compounds. We selected 7-substituted tricyclo[6.3.0.0^2,4>]undecenone derivatives (4) as common key intermediates for both groups, I and II. Both nuclei would be obtained by control in the stereochemistry of the reduction of --- double bond. (+)-3-Carene () was converted to a cyclic β-keto ester in a -step sequence. 4-Methyl derivatives (10 and 11) and 4-CH_2OTBDMS derivatives (12 and 13) were synthesized from . Compound 10 was converted to a tricyclic enone (4a) by allylation at -2, the Wacker oxidation followed by the aldol ring closing reaction. Similarly, the enone 4 was obtained from 12. Stereoselective introduction of a methyl group at -11 of 4 was accomplished to afford 18 and selectively. Deoxygenation of 18 gave (+)-1,2-didehydroaromadendrane (24). Catalytic hydrogenation of afforded a /-trans compound 25 preferentially. The Birch reduction of also produced only 25. Compound 25 was converted to (+)-aromadendrene (1) by reduction of the ketone, esterification with PTC-Cl, radical reductive deoxygenation, deprotection of TBDMS, mesylation followed by elimination with DBU. (-)-Alloaromadendrene (2) was obtained from by an intramolecular-type hydrogen migration occurring in the reduction of the tosylhydrazone with a hydride as a crucial step.

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Five new marine _<29> sterols (2-6) were isolated from the soft coral Sinular ia mayi of the Ishigaki Island, Okinawa. The Spectrosocpic data showed that they are the polyhydroxy derivative of sarcosterol (1), a marine sterol having a unique 23-methyl and a 17(20)-double bond. Sterol 2 was the 25-monohydroxy derivative of 1. The NOE experiment of its 25, 26-didehydro derivative indicated that the stereochemistry at -23 and 24 was identical with that of peridinosterol, whose absolute configuration has previously been established. Sterol 3 was the 25,26-dihydroxy derivative of 1. It was converted to 2 by reductive cleavage of the -26 tosyloxy bond by LAH. Sterols and 6 were shown, by spectroscopic analyses, to be , 25-dihydroxy and ,23,25-trihydroxy derivatives of 1. The stereochemistry in the side chain was derived from interpretation of the coupling pattern and the results obtained by NOE experiments. On storage sterol was found to be converted, by dehydration, to sterol 4 having a tetrahydrofuran ring on the side chain Two new cembranoids sinulariol (7) and mayolide (), simultaenously isolated from S. mayi, were correlated to the known compounds sinulariol A () and mayolide (10) by dehydration. The pyridine-induced deshielding effects, observed in the ^1H NMR spectra of and 10-12, indicated that the absolute configuration at - of to be (R) and that of 10-12 to be (S). A new polyhydroxygorgostane (15) was obtained from the Andaman Sea soft coral Lobophytum strictum. The structure was derived, by spectroscopic data. to be 1β-hydroxy--deoxy derivative of the known compound andamansterol.

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Melithasterols A-D (1-4), isolated from a gorgoinan coral Melithaea ocracea of Okinawa, were shown to be cholestane-, 24-methyl--dehydrocholestane-, -dehydrocholestane-, and 24-methylenecholestane-derivatives. respectively, having a common 3β, 7α -dihydroxy-α, 6α-epoxy-Δ^ steroid nucleus. This was confirmed by direct comparison with the authentic sample prepared by lead tetra-acetate oxydation of cholest-6-ene- 3β, α, α-triol 3-monoacetate. Twelve new polyhydroxysterols were isolated from an Alcyonium sp. (7,,), and Sclerophytum sp. (14,16,19,20,21,a,23,26,28) soft corals collected off the coasts of the Andaman and Nicobar Islands in the Indian Ocean. All the Sclerophytum sp. soft corals contained 17a or its 25-deacetyl derivative. Compounds 7 to were identified as 24-methylenecholest--ene- 3β, 16β-diol-3-0-α-L fucoside (7) and its 7β-() and 7α-hydroxy () derivatives. Compound 14 was shown to be 24S-24-methylcholest--ene-3β,25ξ,26-triol and was correlated to the known compound 15 by α, 6β-glycolation. Compound 16 was shown to be β, 6α-isomer of 17, correlating to 17 by PCC oxidation followed by dehydration. Compound 19 was identified with 25-deacetyl derivative of the known compound lobosterol (19a) by hydrolysis of authentic lobosterol. Compounds 20 and 21 were shown to be 7-dehydro-(20) and -dehydro-(21) derivative of 17a and 17, respectively, by comparisons of their spectral data with reference compounds. Compounds a and 23 were 24S-methylcholestane-3β, α 25-triol-6-one 25-monoacetate (a) and its 25-deacetoxyl derivative (23). Partial PCC oxidation of 17a afforded a. Compounds 26 (andamansterol) and 28 (nicobarsterol) were shown to be gorgost--ene-3β, α. 11α, 21-tetrol and novel secosteroid, 11,21-cyclo--homo-11-oxa-, 11-secoergostane-3β, 6α, 12ξ-triol--one, respectively, by spectral analyses (H-HCOSY, HMQC, HMBC).

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The phase diagrams of the Ni-Mo- and Ni-W- ternary systems in the region of less than 50mol% were constructed by thermodynamic calculation, based on the data obtained by thermodynamic measurement of the related materials. We found three ternary eutectic points and three or two ternary peritecto-eutectic points as follows:
:L (1365K, 71.mol%Ni-6.0mol%Mo-.mol%)=(Ni)++
:L (1355K, 62.mol%Ni-2.mol%Mo-30.mol%)=++
:L (1445K, 42.0mol%Ni-30.6mol%Mo-10.3mol%)=(Ni)+NiMo+
P₁:L (1812K, 34.mol%Ni-42.3mol%Mo-.mol%)+MoB=+
P₂:L (1633K, 42.3mol%Ni-40.4mol%Mo-17.3mol%)+Mo=+
P₃:L (1812K, 53.mol%Ni-33.7mol%Mo-12.mol%)+Mo=NiMo+
:L (1622K, 51.0mol%Ni-31.6mol%W-17.4mol%)=(Ni)+W+
:L (1260K, 71.0mol%Ni-7.0mol%W-.0mol%)=(Ni)++
:L (1291K, 65.4mol%Ni-4.mol%W-29.mol%)=++
P₁:L (2115K, 23.mol%Ni-43.1mol%W-33.1mol%)+WB=+
P₂:L (1657K, 48.mol%Ni-33.1mol%W-18.0mol%)+=W+
The calculated phase diagrams are expected to be useful for the development of new Ni-based heat-, corrosion- or wear-resistance alloys.

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This report describes a patient with extramedullary relapse of acute myeloid leukemia (AML) without involving bone marrow. A 57-year-old man was diagnosed as having acute monoblastic leukemia with t(;11)(p;q23) and trisomy . Ten months after achieving complete response (CR) with chemotherapy, masses developed in his left forearm and in the back of his thigh, preceded by enigmatic peripheral neurological symptoms. Aspiration from the forearm showed leukemic relapse, and fluorescence in situ hybridization (FISH) revealed that the majority of the cells had 11q23 anomaly and tetrasomy . Bone marrow or meningeal relapse was not observed. To our knowledge, this is the first case report of clonal evolution associated with the development of myeloid sarcoma as a relapse in AML.

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Six new cembranoids sarcophytol P (3), R (4), S (), K (), F (11), and T (13) were isolated from the soft coral Sarcophyton glaucum. Sarcophytol P (3) was shown to be the 20-hydroxy derivative of the major component sarcophytol A (1), and afforded the cyclization product 6 in CHCl_3 at room temperature, in a same way as in 1. Sarcophytols R (4) and S () were correlated to 1, by conversion of its 7R,R and 7S,S epoxide derivatives. Sarcophytol K() was a 13, 14-dihydroxycembranoid having a 1,3Z-diene moiety. The absolute configuration of and its 1Z,3- and 1Z,3Z-isomers sarcophytol (2) and J (10) were determined by circular dichroism study of their bis-p-dimethylaminobenzoate derivatives. Sarcophytols F (11) and T (13) were 1- and 1,3Z-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 F (11, 1,3), N (15, 1Z,3Z) and T (13,1,3Z), spontaneous autoxidation-cyclization, in CHCl_3,was examined, in order to compare the stereochemical course of the reaction with that of 1 (1Z,3), which affords trans-fused bicyclo[.3.0]tetradecene systems. The 1,3Z-isomer 13 gave the same cyclization product 18, as in the reaction of 1, even though it is isomeric at -1,3. The 1Z,3Z isomer 15 gave 19, in consequence of the reversed geometry at -3 of 15. The 1,3-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 -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 -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 (30), the parent hydrocarbon of 1, also reacted in CHCl_3 giving the bicyclic product 32.

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Brassinolide analogues, (R, 23R, 24R)-2α, 3α, , 23-tetrahydroxy--homo-7-oxa--ergostan-6-one (24-epibrassinolide) (10) and (S, 23S, 24R)-2α, 3α, , 23-tetrahydroxy--homo-7-oxa--ergostan-6-one (), were synthesized from brassicasterol (3a) in five steps and with ca. 20% overall yield. The key steps are the direct formation of (, 24R)-3α, -cyclo--ergost--en-6-one (4) from brassicasterol mesylate (3), the acid-catalyzed rearrangement of 4 to (, 24R)--ergosta-2, -dien-6-one (6), and the Baeyer-Villiger oxidation of the tetrahydroxy -ergostan-6-ones 7 and .

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The aim of the present study was to examine the survival rate of embryos after bilateral nonsurgical transfer in recipient cows given a superovulatory treatment of low-dose FSH. In total, 54 parous Holstein or Japanese Black breed cows were used as recipients. These recipients were assigned to the three groups based on hormonal treatments during the preceding estrous cycle. The treatments included A) FSH (10 or 15 mg) and PGF_2α (n=18), ) PGF_2α (n=14), and ) no treatment (n=). Morula to blastocyst-staged embryos that were transferred were derived either from in vitro maturation & in vitro fertilization or they were collected from superovulated Japanese Black heifers. Some embryos collected from donors were routinely frozen and thawed. Most of the cows (83%, 15/18) that were given the combination of FSH and PGF₂α formed corpora lutea (CLs) on the ovaries (mean number CLs ± s.. per cow=3.1 ± 0.48). Pregnancy rates on day 30 in groups A, and were 67% (12/18), 64% (/14) and 55% (12/), respectively (P>0.05). The rates of twin pregnancies to all pregnancies were 50% (6/12), % (2/) and 42% (/12), respectively (P>0.05). Consequently, 19 cows carried their pregnancies to term, producing 25 calves, including six pairs of twins. Calving rates in the three groups were 67% (/12), 33% (3/), and 67% (/12), respectively (P>0.05). Calf crop rates were 125% (10/), 133% (4/3), and 138% (11/), respectively (P>0.05). The embryonic survival rate at Day 30 in group A was likely to be higher than those of cows in the other two groups (50% [18/36] vs 39% [28/72]). No difference between the origins of embryos was observed in the embryonic survival rates. These results suggested that superovulatory treatment with low-dose FSH to recipients bilaterally receiving embryos would be beneficial for increasing embryonic survival, although the results were not statistically significant.

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