Asymmetric Total Synthesis of Fredericamycin A

Seventeen years after the isolation of the promising antitumor antibiotic fredericamycin A, the first asymmetric total synthesis of this compound has been accomplished and thereby its absolute configuration established. The key feature is the regiocontrolled [4+2] cycloaddition of 3 to 2 , which was obtained by the stereospecific rearrangement of 1 . Cp = (−)‐camphanoyl.     

Synthesis and biological evaluation of γ-fluoro-β,γ-unsaturated acids

Several γ-fluoro-β,γ-unsaturated acids, fluorine-containing analogues of N-acyl glycines, were synthesized via Julia-Lythgoe olefination. The antimicrobial activities of these compounds and synthetic intermediates were evaluated. Analogues with an octyl group showed in vitro antifungal activity agaist Penicillium chrysogenum IFO4626.     

Enantioselective total synthesis of a potent antitumor antibiotic, fredericamycin A.

The asymmetric total synthesis of both enantiomers of the potent antitumor antibiotic fredericamycin A (1) is detailed based on the protocol for the construction of its peri-hydroxy polyaromatic skeleton bearing the chirality at the spiro carbon via a strong base-induced cycloaddition of suitably substituted homophthalic anhydrides (AB-ring unit) with an optically active CDEF-ring unit. Particular attention has been given to the novel synthesis of the optically active spiro carbon center by a stereospecific rearrangement of optically active benzofuzed-trans-epoxy acylates leading to spirocyclopentane-1,1'-indane systems. This method is quite useful for the construction of an optically active spiro compound and was applied to the synthesis of the optically pure CDEF-ring unit of 1. Cycloaddition of the optically pure CDEF-ring unit to AB-ring units prepared via benzyne afforded two natural and unnatural-type hexacyclic compounds, which were converted to natural and unnatural enantiomers of synthetic 1, and the absolute configuration of natural 1 was determined as S.     

Kaonic nuclear state search via reaction at rest on He target

Very recently, we have performed a couple of experiments, KEK PS-E549/E570, for the detailed study of the strange tribaryon S⁰(3115) obtained in KEK PS-E471. In contrast to the previous proton spectrum, no narrow (20 MeV) peak structure was found either in the inclusive ⁴He(stopped K⁻, p) or in the semi-inclusive ⁴He(stopped K⁻, pX^±) reaction channel, which is equivalent to the previous E471 event trigger condition. Detailed analysis of the present data and simulation shows that the peak, corresponding to S⁰(3115), has been an experimental artifact. Present analysis does not exclude the possible existence of a much wider structure.     

Sensitivity and precision of the 13C-breath test

Sensitivity and precision of the 13C-breath test were assessed by examining a couple of limiting factors caused by the sensitivity of the instrument used for 13CO2 analysis, endogenous fluctuation of 13CO2 abundance, and the residual CO2 in sample storing tubes, vacutainers, etc. For 13CO2 analysis, a mass spectrometer equipped with a dual inlet, a dual collector, and an automated pressure matching system, was used. 15 ml vacutainers were used for sample storage. Endogenous fluctuation of 13CO2 abundance, however, was measured by putting the breath samples directly into the evacuated CO2 purification system, instead of using vacutainers. Endogenous fluctuation (S.D. = 0.202%) was the most significant limiting factor, compared with instrumental limitation (0.085%), or with influence of the residual CO2 (0.136%). Consequently, the sensitivity of the 13C-breath test was figured out to be 0.52%. This sensitivity is about 1,000 times lower than that of 14C-breath test. The precision was linearly dependent on 13C increase from basal 13C observed after administration of 13C enriched compounds, delta 13C, and was determined to be expressed as 1.94 delta 13C.     

Chiral ligand exchange micellar electrokinetic chromatography using borate anion as a central ion

Three compounds having 1,2-diol structure (1-phenyl-1,2-ethanediol, 3-phenoxy-1,2-propanediol, and 3-benzyloxy-1,2-propanediol) were enantioseparated by ligand exchange MEKC using (5S)-pinanediol (SPD) as a chiral selector and borate anion as a central ion together with SDS. When (S)-1,2-propanediol, (S)-1,2,4-butanetriol, or (S)-3-tert-butylamino-1,2-propanediol were used as the chiral ligand instead of SPD, these three compounds were not enantioseparated. When borate was replaced with 2-aminoethane-1-sulfonate or N-cyclohexyl-3-aminopropanesulfonate, no chiral separation was achieved. Therefore, the hydrophobic interaction between the chiral selector and the chiral analytes within the transient diastereomeric complex may play an important role in the enantioseparation achieved by the proposed method.     

SOL-detectability of liver SPECT--analysis by SOL detection model

The purpose of this study is to evaluate the clinical efficacy of liver SPECT (single photon emission computed tomography). Eleven hospitals which are in or near Tokyo are participating in this study. Planar liver images and SPECT images of 134 cases which were retrospectively confirmed for its final diagnosis were collected. At the first study, the planar images (PS) were read by 13 nuclear medicine physicians. The second, the image reading by the combination of the planar images and the SPECT images (PS + SPECT) were performed. The confidence level of diagnosis for SOL (space occupying lesion) obtained by the image reading of PS and PS + SPECT has been analyzed by using the SOL detection model. The SOL detectability of PS + SPECT was higher than that of PS only. However, these differences were not statistically significant.