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The antibacterial activity of a novel cephalosporin derivative, CP6162, possessing a dihydroxypyridone moiety at the C-3 side chain, was evaluated in vitro and in vivo, with ceftazidime, aztreonam and cefoperazone as the reference antibiotics. CP6162 showed weak or little activity against Gram-positive bacteria, but potent activity against clinical isolates of the Gram-negative species including strains of Pseudomonas aeruginosa, Ps. cepacia, Acinetobacter sp., Xanthomonas maltophilia, Serratia marcescens, Enterobacter cloacae and Citrobacter freundii, which were resistant to the reference antibiotics. The MICs of CP6162 were only slightly affected by the high producers of beta-lactamases except for cephalosporinase-producing C. freundii. It was, however, affected by the presence of ferric ion. CP6162 showed in-vivo activity paralleling the in-vitro activity, and also showed pharmacokinetic parameters similar to those of ceftazidime in mice and rats. [ABSTRACT FROM AUTHOR]

The fate of fission-product iodine is critical for the deployment of next generation molten salt reactor technologies, owing to its volatility and biological impacts if it were to be released into the environment. To date, little is known on how ionizing radiation fields influence the redox chemistry, speciation, and transport of iodine in high temperature molten salts. Here we employ picosecond electron pulse irradiation techniques to elucidate for the first time the impact of iodide ions (I - ) on the speciation and chemical kinetics of the primary radiation-induced transient radicals generated in molten chloride salt mixtures (e S - and Cl 2 ˙ - ) as a function of temperature (400-700 °C). In the presence of I - ions (≥ 1 wt% KI in LiCl-KCl eutectic), we find that the transient spectrum following the electron pulse is composed of at least three overlapping species: the e S - and the Cl 2 ˙ - and ICl˙ - radical anions, for which a deconvoluted spectrum of the latter is reported here for the first time in molten salts. This new transient spectrum was consistent with gas phase density functional theory calculations. The lifetime of the e S - was unaffected by the addition of I - ions. The newly observed interhalogen radical anion, ICl˙ - , exhibited a lifetime on the order of microseconds over the investigated temperature range. The associated chemical kinetics indicate that the predominate mechanism of ICl˙ - decay is via reaction with the Cl 2 ˙ - radical anion. The iodine containing product of this reaction is expected to be ICl 2 - , which will have implications for the transport of fission-product iodine in MSR technologies.

Molten chloride salts are currently under consideration as combined coolant and liquid fuel for next-generation molten salt nuclear reactors. Unlike complementary light-water reactor technologies, the radiation science underpinning molten salts is in its infancy, and thus requires a fundamental mechanistic investigation to elucidate the radiation-driven chemistry within molten salt reactors. Here we present an electron pulse radiolysis kinetics study into the behaviour of the primary radiolytic species generated in molten chloride systems, i.e. , the solvated electron (e S - ) and di-chlorine radical anion (Cl 2 ˙ - ). We examine the reaction of e S - with Zn 2+ from 400-600 °C ( E a = 30.31 ± 0.09 kJ mol -1 ), and the kinetics and decay mechanisms of Cl 2 ˙ - in molten lithium chloride-potassium chloride (LiCl-KCl) eutectic. In the absence of Zn 2+ , the lifetime of e S - was found to be dictated by residual impurities in ostensibly "pure" salts, and thus the observed decay is dependent on sample history rather than being an intrinsic property of the salt. The decay of Cl 2 ˙ - is complex, owing to the competition of Cl 2 ˙ - disproportionation with several other chemical pathways, one of which involves reduction by radiolytically-produced Zn + species. Overall, the reported findings demonstrate the richness and complexity of chemistry involving the interactions of ionizing radiation with molten salts.

Ferroelectricity in fluid materials, which allows free rotation of molecules, is an unusual phenomenon raising cutting-edge questions in science. Conventional ferroelectric liquid crystals have been found in phases with low symmetry that permit the presence of spontaneous polarization. Recently, the discovery of ferroelectricity with high symmetry in the nematic phase has attracted considerable attention. However, the physical mechanism and molecular origin of ferroelectricity are poorly understood and a large domain of macroscopically oriented spontaneous polarization is difficult to fabricate in the ferroelectric nematic phase. This study reports new fluid layered ferroelectrics with the C ∞v symmetry in which nearly complete orientation of the spontaneous polarization remains stable under zero electric field without any orientation treatment. These ferroelectrics are obtained by simplifying the molecular structure of a compound with a known ferroelectric nematic phase, although the simplification reduced the dipole moment. The results provide useful insights into the mechanism of ferroelectricity due to dipole-dipole interactions in molecular assemblies. The new ferroelectric materials are promising for a wide range of applications as soft ferroelectrics., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Room temperature post-irradiation measurements of diffuse reflectance and electron paramagnetic resonance spectroscopies were made to characterize the long-lived radiation-induced species formed from the gamma irradiation of solid KCl, MgCl2, and ZnCl2 salts up to 100 kGy. The method used showed results consistent with those reported for electron and gamma irradiation of KCl in single crystals. Thermal bleaching of irradiated KCl demonstrated accelerated disaggregation of defect clusters above 400 K, due to decomposition of Cl3-. The defects formed in irradiated MgCl2 comprised a mixture of Cl3-, F-centers, and Mg+ associated as M-centers. Further, Mg metal cluster formation was also observed at 100 kGy, in addition to accelerated destruction of F-centers above 20 kGy. Irradiated ZnCl2 afforded the formation of Cl2- due to its high ionization potential and crystalline structure, which decreases recombination. The presence of aggregates in all cases indicates the high diffusion of radicals and the predominance of secondary processes at 295 K. Thermal bleaching studies showed that chloride aggregates' stability increases with the ionization potential of the cation present. The characterization of long-lived radiolytic transients of pure salts provides important information for the understanding of complex salt mixtures under the action of gamma radiation.

To facilitate the development of molten salt reactor technologies, a fundamental understanding of the physical and chemical properties of molten salts under the combined conditions of high temperature and intense radiation fields is necessary. Optical spectroscopic (UV-Vis-near IR) and electrochemical techniques are powerful analytical tools to probe molecular structure, speciation, thermodynamics, and kinetics of solution dynamics. Here, we report the design and fabrication of three custom-made apparatus: (i) a multi-port spectroelectrochemical furnace equipped with optical spectroscopic and electrochemical instrumentation, (ii) a high-temperature cell holder for time-resolved optical detection of radiolytic transients in molten salts, and (iii) a miniaturized spectroscopy furnace for the investigation of steady-state electron beam effects on molten salt speciation and composition by optical spectroscopy. Initial results obtained with the spectroelectrochemical furnace (i) and high-temperature cell holder (ii) are reported.

A versatile, compact heater designed at National Synchrotron Light Source-II for in situ X-ray nano-imaging in a full-field transmission X-ray microscope is presented. Heater design for nano-imaging is challenging, combining tight spatial constraints with stringent design requirements for the temperature range and stability. Finite-element modeling and analytical calculations were used to determine the heater design parameters. Performance tests demonstrated reliable and stable performance, including maintaining the exterior casing close to room temperature while the heater is operating at above 1100°C, a homogenous heating zone and small temperature fluctuations. Two scientific experiments are presented to demonstrate the heater capabilities: (i) in situ 3D nano-tomography including a study of metal dealloying in a liquid molten salt extreme environment, and (ii) a study of pore formation in icosahedral quasicrystals. The progression of structural changes in both studies were clearly resolved in 3D, showing that the new heater enables powerful capabilities to directly visualize and quantify 3D morphological evolution of materials under real conditions by X-ray nano-imaging at elevated temperature during synthesis, fabrication and operation processes. This heater design concept can be applied to other applications where a precise, compact heater design is required.

Background: Only limited data are available concerning the long-term outcomes of imatinib treatment among Japanese or Asian patients with advanced or recurrent gastrointestinal stromal tumors (GIST). Our multicenter study, which was conducted in northern Kanto, Japan, aimed to assess the efficacy of imatinib mesylate against advanced or recurrent GIST., Summary: The clinicopathological data of 234 GIST patients who were treated at one of the 11 participating hospitals from 2001 to 2011 were retrospectively reviewed (GREAT study). Imatinib was administered as a first-line therapy in cases involving unresectable disease or postoperative recurrence (41 cases). The patients treated with imatinib (n = 41) exhibited 1-, 3-, and 5-year overall survival (OS) rates of 92.3, 74.9, and 53.8% respectively. In univariate and multivariate analyses, imatinib continuation with dose reduction and achieving a complete or partial response were found to be associated with increased OS. The results of 2 large-scale, long-term trials demonstrate that the risk of tumor progression decreases with increased treatment duration. Furthermore, the interruption of imatinib treatment in responsive and controlled patients results in a high risk of disease progression. Key Messages: Long-term imatinib treatment is recommended for patients with nonprogressive disease. If patients experience significant toxicities, temporary dose reduction and treatment continuation might be useful., (© 2018 S. Karger AG, Basel.)

Although exercise oscillatory ventilation has emerged as a potent independent risk factor for adverse prognosis in heart failure, it is not well known whether cardiac rehabilitation can improve oscillatory ventilation. In this study, we investigated the magnitude of oscillations in ventilation before and after cardiac rehabilitation in chronic heart failure patients with exercise oscillatory ventilation. Cardiac rehabilitation (5-month program) was performed in 26 patients with chronic heart failure who showed an oscillatory ventilation pattern during cardiopulmonary exercise testing (CPX). After the 5-month rehabilitation program was completed, the patients again underwent CPX. To determine the magnitude of oscillations in ventilation, the amplitude and cycle length of the oscillations were calculated and compared with several other parameters, including biomarkers that have established prognostic value in heart failure. At baseline before cardiac rehabilitation, both oscillation amplitude (R = 0.625, P < 0.01) and cycle length (R = 0.469, P < 0.05) were positively correlated with the slope of minute ventilation vs. carbon dioxide production. Plasma BNP levels were positively correlated with amplitude (R = 0.615, P < 0.01) but not cycle length (R = 0.371). Cardiac rehabilitation decreased oscillation amplitude (P < 0.01) but failed to change cycle length. The change in amplitude was positively correlated with the change in BNP levels (R = 0.760, P < 0.01). Multiple regression analysis showed that only the change in amplitude was an independent predictor of the change in BNP levels (R = 0.717, P < 0.01). A 5-month cardiac rehabilitation program improves exercise oscillatory ventilation in chronic heart failure patients by reducing the oscillation amplitude. This effect is associated with a reduction of plasma BNP levels, potentially contributing to an improvement of heart failure.

Background: Dysphagia is a serious health problem in aging populations. Older persons also experience high rates of chronic illness and hospitalization. Accurate identification of dysphagia at the time of hospital admission is important for providing supportive interventions for effective swallowing and preventing complications of dysphagia., Objectives: This study aimed to estimate the prevalence of potential impairment of swallowing function, the association between self-reported and observed swallowing difficulty, and factors associated with swallowing impairment in hospitalized patients., Methods: Data from 11,963 patients who were admitted to a community hospital from July 2012 to June 2014 were used. Patients responded to a brief self-administered questionnaire (BSAQ) about swallowing difficulties and performed a modified water swallow test (MWST) using a standardized protocol. Sensitivity and specificity of the BSAQ were evaluated against swallowing impairment based on the MWST. Logistic regression analysis was performed to evaluate associations between background characteristics and impaired swallowing as evaluated by the screening tests., Results: Median age of patients was 73 years (interquartile range, 63-81 years), and 5,780 (48.3%) were women. On the BSAQ, a total of 3,026 patients reported severe symptoms in any of 15 dysphagia-related questions (253 per 1,000 patients). The MWST showed that 593 patients were unable to successfully swallow 3 ml of cold water without choking or experiencing wet hoarseness two times within 30 seconds (50 per 1,000 patients). Each item score and the total score of the BSAQ were significantly associated with impaired swallowing as evaluated by the MWST. The sensitivity and specificity of the BSAQ for impaired swallowing as evaluated by the MWST were 72% and 66%, respectively. The prevalence of impaired swallowing as evaluated by both tests increased with age-especially in patients of ages ≥80 years. Age, male gender, and underlying diseases, including neurological and respiratory diseases, were associated with swallowing dysfunction detected by the MWST., Discussion: Impaired swallowing function may frequently be present in older hospitalized patients. The clinical significance of the validated screening tests in nursing practice should be further studied.

It has been suggested that n-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against cardiovascular diseases, and EPA/arachidonic acid (AA) and DHA/AA ratios in serum are potential risk markers for coronary artery disease (CAD). The purpose of this study was to clarify the clinical significance of the difference in the EPA/AA ratio and the DHA/AA ratio in patients with CAD. In 369 patients with confirmed or suspected CAD who underwent diagnostic coronary angiography, we measured serum levels of EPA, DHA and AA and calculated the EPA/AA and DHA/AA ratios. The EPA/AA ratio was significantly lower in patients with acute coronary syndrome (ACS) than in patients with chronic CAD or chest pain syndrome (0.27±0.19 vs. 0.44±0.20, respectively; P<0.01), whereas the DHA/AA ratio was similar in the two groups (0.78±0.27 vs. 0.79±0.37). Multiple logistic regression analyses using various biomarkers related to coronary risk discriminated ACS from other disease entities and demonstrated that the EPA/AA ratio (odds ratio: 0.0012, 95% confidence interval: 0.00-0.16, P<0.01) but not the DHA/AA ratio (odds ratio: 1.05, 95% confidence interval: 0.98-1.12) was a significant independent predictive factor. Our findings suggest that the EPA/AA ratio might be more closely associated with the pathophysiology of CAD, especially with that of ACS, than the DHA/AA ratio. Our findings suggest that interventions with EPA agents or supplemental EPA intake, compared with DHA agents or supplemental DHA, may confer greater benefit for plaque stabilization to prevent the onset of ACS in patients with CAD.

We have developed a system for measuring the temporal profiles of scintillation at high linear energy transfer (LET) by using pulsed ion beams from a cyclotron. The half width at half maximum time resolution was estimated to be 1.5-2.2 ns, which we attributed mainly to the duration of the pulsed ion beam and timing jitter between the trigger signal and the arrival of the ion pulse. The temporal profiles of scintillation of BaF2 at different LETs were successfully observed. These results indicate that the proposed system is a powerful tool for analyzing the LET effects in temporal profiles of scintillation.

A new series of 1beta-methyl carbapenems possessing a 6,7-disubstituted imidazo[5,1-b]thiazol-2-yl group directly attached to the C-2 position of the carbapenem nucleus was prepared, and their activities against methicillin-resistant Staphylococcus aureus (MRSA) were evaluated. First, a benzyl moiety was introduced at the C-6 position of imidazo[5,1-b]thiazole attached to the carbapenem. These benzylated molecules showed potent anti-MRSA activity, but poor water solubility. In order to overcome this drawback, we designed and synthesized di- and tricationic carbapenems and finally discovered a novel carbapenem (15i), which exhibited excellent anti-MRSA activity and good water solubility.

A new series of 1beta-methyl carbapenems possessing a 6,7-disubstituted imidazo[5,1-b]thiazol-2-yl group directly attached to the C-2 position of the carbapenem nucleus was prepared, and the activities of these compounds against methicillin-resistant Staphylococcus aureus (MRSA) were evaluated. To study the effect of basic moieties on anti-MRSA activity, we introduced an amino, or imino, or amidino group at the 6-position of imidazo[5,1-b]thiazole in place of the carbamoylmethyl moiety of CP5068. Anti-MRSA activities of almost all basic group-substituted carbapenems were improved, though some of the compounds showed stronger acute toxicity in mice than IPM. In order to decrease the toxicity without decreasing the activity, we introduced various additional functionalities around the basic moiety. Finally, we obtained CP5484, which has excellent anti-MRSA activity and low acute toxicity.

A new series of 1beta-methyl carbapenems, possessing a 7-substituted imidazo[5,1-b]thiazol-2-yl group directly attached to the C-2 position of the carbapenem nucleus, was synthesized and evaluated for antibacterial activity. These compounds showed potent activities against Gram-positive bacteria, in particular methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP). They also exhibited potent activity against beta-lactamase-negative ampicillin-resistant Haemophilus influenzae (BLNAR).

A series of 1beta-methylcarbapenems bearing an (imidazo[5,1-b]thiazolium-6-yl)methyl moiety, a 5,5-fused heterobicycle, at the C-2 position was synthesized and evaluated for in vitro antibacterial activities. CP0569 (1r) and its analogues showed potent antibacterial activities against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and Gram-negative bacteria, including Pseudomonas aeruginosa. Moreover, CP0569 (1r) exhibited stronger antibacterial activity against MRSA and higher resistance to renal dehydropeptidase-1 (DHP-1) than any currently marketed carbapenems, that is, imipenem (IPM), panipenem (PAPM), and meropenem (MEPM).

A series of cephalosporins bearing a 5,5-fused ring system, an (imidazo[5,1-b]thiazolium-6-yl)methyl group, at the C-3 position were synthesized and evaluated for in vitro antibacterial activities. CP6679 (1s) and its analogues showed potent antibacterial activities against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. They were also highly active against methicillin-resistant Staphylococcus aureus (MRSA). CP6679 (1s) showed more potent antibacterial activity than ceftazidime (CAZ) or cefpirome (CPR) against Pseudomonas aeruginosa and MRSA.

A series of cephalosporin derivatives with a thiazolopyridinium group at the 3-position was synthesized and evaluated for antibacterial activity. Some of these cephalosporin derivatives having a (5-alkylthiazolo[4,5-c]pyridinium-2-yl)thiomethyl group at the 3-position showed strong activity against Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa. Among them, 5a showed a good antibacterial spectrum in vitro, and also showed a similar or slightly superior activity to that of ceftazidime in vivo against P. aeruginosa.

A series of cephalosporin derivatives with various bicyclic heterocycles at the C-3 position was synthesized and evaluated for antibacterial activity. Among them CP0467 (3a) showed excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) (MIC90 = 6.25 microg/mL), and extremely high affinity for the penicillin binding protein 2' of MRSA (I50 = 0.49 microg/mL). Furthermore, 3a showed a long-acting pharmacokinetic profile in mice (AUC(infinity) = 482.3 microg/h/mL and T(1/2) = 1.9 h).

A new 5-HT3 receptor ligand, CP2289, was synthesized and pharmacologically tested. Although CP2289 inhibited the Bezold-Jarisch reflex, it contracted the excised ileal muscle of mice, rats and guinea pigs. This response may reflect a partial agonist character of CP2289 in the gut. In vivo antiemetic and gastric emptying tests gave similar results.

Synthesis and antibacterial activity of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(3-(3-hydroxy-4-pyridon-1-y l)-3- carboxypropoxyimino)acetamido]-3-(1,2,3-thiadiazol-5-yl)thio methyl-3-cephem-4-carboxylic acid (12a) and its related compounds are described. Compound 12a exhibited excellent antibacterial activity against gram-negative bacteria, including Pseudomonas aeruginosa.

The synthesis and biological activity of a series of 3-[2-(5-hydroxy-4-pyridon-2-yl)ethenyl]cephalosporin derivatives are described. They showed very potent activity against Gram-negative bacteria, especially Pseudomonas aeruginosa. (6R, 7R)-7-[(Z)-2-(2-Aminothiazol-4-yl)-2 -(1-carboxy-1-methyl)-ethoxyiminoacetamido]-3-[(Z)-2-(1,5-dihydrox y-4- pyridon-2-yl)ethenyl]ceph-3-em-4-carboxylic acid, CP6162 (8e), was selected for further evaluation as antipseudomonal chemotherapeutic agent.

Substituted (cyclopentenopyridinium)thiomethyl groups were introduced as C-3 substituents of (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-oxyimino]acetami docephalosporins. Structure-activity relationships of this class of cephalosporins are discussed on the basis of their MIC. The selected compounds, 3a and 4a (ME1221), having an acidic substituent, showed excellent in vivo efficacy and low toxicity.

Synthesis and antibacterial activity of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxy-1-methyl)ethoxyimin oacetamido]- 3-(3-hydroxy-4-pyridon-1-yl)-3-cephem-4-carboxylic acid (12) and its related compounds are described. Compound 12 exhibited excellent antibacterial activity against gram-negative bacteria, and its anti-pseudomonal activity was ten to fifteen times greater than that of ceftazidime.

A practical synthetic method for large scale production of MT0703, (6R,7R)-7-[(RS)-2-(2-aminothiazol-4-yl)-2-(1,5-dihydroxy-4-pyridon e-2- carboxamido)acetamido]-3-[[1-(2-hydroxyethyl)pyridinium-4- yl]thiomethyl]ceph-3-em-4-carboxylate, was established. Its two diastereomers on configuration of the aminothiazolylglycyl moiety were synthesized using chemico-enzymatic method. The S-isomer of MT0703 was found to be more active against Gram-positive and Gram-negative bacteria including beta-lactamase-producing strains than the R-isomer.

A series of new aminothiazolylglycylcephalosporins with a mono- or dihydroxypyridonecarbonyl group at the alpha-amino group of the C-7 substituent have been prepared and antibacterial activity of these compounds was investigated. Among them, the compounds having a 1,5-dihydroxy-4-pyridone-2-carbonyl group showed excellent anti-pseudomonal activity. In particular, (6R,7R)-7-[(RS)-2-(2-aminothiazol-4-yl)-2-(1,5-dihydroxy-4- pyridone-2-carboxamido)- acetamido]-3-[[1-(2-hydroxyethyl)pyridinium-4-yl]thiomethyl]ceph-3 -em- 4-carboxylate (MT0703, 7g) was found to be a well balanced compound with respect to antibacterial activity.

The antibacterial activity of a novel aminothiazolylglycylcephalosporin, MT0703S, possessing a dihydroxypyridone moiety was compared in vitro with the activity of ceftazidime, cefoperazone, aztreonam and other beta-lactam antibiotics using seven bacterial species of a clinical origin. MT0703S showed the most potent activity against P. aeruginosa, including the ceftazidime-resistant strains, E. coli, K. pneumoniae and C. freundii. MT0703S was comparable to aztreonam but more active than ceftazidime and cefoperazone in its activity against K. oxytoca and E. cloacae, and comparable to ceftazidime against S. aureus and S. marcescens. MT0703S was more active than cefoperazone against S. marcescens but less active against S. aureus. The stability of MT0703S against various beta-lactamases appeared to be intermediate between the stability of ceftazidime and that of cefoperazone. The antimicrobial activity of MT0703S increased in a low-iron environment and decreased in a high ferric ion concentration.

By the use of HPLC technique after treatment with beta-lactamases, two novel cephamycins, SF-1623 and SF-1623B, were discovered and isolated from the fermentation broth of Streptomyces chartreusis SF-1623. The structures of SF-1623 and SF-1623B were determined to contain 3-sulfothiomethyl and 3-hydroxymethyl groups respectively, by chemical and enzymatic transformation reactions. Studies on the fermentation condition and process for the large scale preparation of antibiotic SF-1623 are also described.

The effect of chemical modification of the D-amino acid function, which represents the C-7 beta substituent of cephamycin MT-141 on in vitro antibacterial activity was examined. MT-141 was more active on Gram-negative organisms than Gram-positive ones. It showed strong bacteriolytic activity on Gram-negative organisms. Lysis of Escherichia coli K-12 strain JE1011 treated with a low concentration of this antibiotic was preceded by frequent formation of multiple bulges from the cells. Amidation or decarboxylation, removing the acidic function from the D-amino acid of MT-141, resulted in an increase in activity against Gram-positive bacteria, and a decrease against Gram-negative ones. Cells treated with the amide or the decarboxylate did not form multiple bulges but formed single bulges. N-Acetylation of the D-amino acid moiety removing the basic function, caused a marked drop in activity against both Gram-positive and Gram-negative bacteria. The bacteriolytic activity on E. coli was reduced, and cells treated with the N-acetate became filamentous. Conversion of the D-amino acid function of MT-141 to the L configuration caused a moderate drop in activity against both Gram-positive and Gram-negative organisms. Both bacteriolytic and bactericidal activities against E. coli were reduced in the L-congener. Cefoxitin, cefmetazole and latamoxef used as reference antibiotics were less active than MT-141 in the bactericidal activity against E. coli, and induced single bulge formation or filamentation of the cells around MIC levels. Cell-surface permeability, stability to beta-lactamases, and binding affinity to PBPs of E. coli did not differ between MT-141 and its derivatives.

Oligostatins C, D and E, three new antibiotics were found in the culture filtrate of Streptomyces myxogenes nov. sp. SF-1130. Their spectral and chemical properties suggested that oligostatins were basic oligosaccharide antibiotics. They exhibited not only antibacterial activity but also strong amylase inhibitory activity.

Treatment of 9-trichloroacetylmidecamycin with aqueous alkali gave an isomer of midecamycin (neoisomidecamycin), in which one double bond underwent allylic rearrangement. The formation of neoisomacrolides was dependent on the nature of protective groups and conditions of deprotective reaction. Treatment of 9-trichloroethoxycarbonylmidecamycin with Zn/acetic acid resulted in no allylic rearrangement.

Treatment of 9,2'-diacetylmidecamycin (2) with DMSO and acetic anhydride afforded 3''-methylthiomethyl derivative (3) preferably in the presence of pyridine. Reaction of midecamycin (1) with DMSO and acetic anhydride gave 2'-acetyl-9-dehydro-3''-methylthiomethyl derivative (9) indicating that the three hydroxyl groups reacted in a different way to the reagent. When compound 2 was reacted with DMSO and acetic anhydride in the presence of CCl4, 3''-acetoxymethyl derivative (13) was a major product, which was formed via 3 through the Pummerer rearrangement. The structures of 3, 9 and 13 were confirmed by examining NMR and mass spectra of these compounds and their deuterio analogue. They showed antimicrobial spectra similar to 1 but superior in vivo activity.