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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Society of Synthetic Organic Chemistry, Japan  

DOI： 10.5059/yukigoseikyokaishi.80.766

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Pharmaceutical Society of Japan  

Habiterpenol is a G2 checkpoint inhibitor isolated from the culture broth of Phytohabitans sp. 3787_5. Here, we report the synthesis of new habiterpenol analogs through the total synthesis process of habiterpenol and evaluating the analogs for G2 checkpoint inhibitory activity. We investigated two different synthetic approaches for total synthesis, with intramolecular conjugate addition and Ti(III)-mediated radical cyclization as key reactions. Although the former was unsuccessful, the latter reaction facilitated stereoselective total synthesis and determination of the absolute configuration of habiterpenol. The extension of these chemistries to a structure-activity relationship (SAR) study gave new habiterpenol analogs, which could not be derived from natural habiterpenol and only be synthesized by applying the total synthesis. Therefore, this study provides important insights into SAR studies of habiterpenol.

DOI： 10.1248/cpb.c21-00993

PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

<title>Abstract</title><sec>
<title>Background</title>
In clinical practice, a mixed suspension of clopidogrel bisulfate and magnesium oxide (MgO) tablets is administered frequently via a feeding tube. However, there is no report on the changes occurring when suspensions of these two drugs are combined, including the effects or potential decrease in dose following tube administration. Thus, the purpose of our study was to investigate the (i) changes caused by mixing clopidogrel bisulfate (ion form) and MgO tablets and (ii) effects on the administered clopidogrel dose after passing through a feeding tube.


</sec><sec>
<title>Methods</title>
The molecular structure of clopidogrel generated in a mixture of clopidogrel bisulfate and a basic compound, such as sodium bicarbonate or MgO tablet, was determined by ¹H-NMR after extraction and purification. The suspension of clopidogrel bisulfate tablet alone and the mixed suspension of clopidogrel bisulfate tablet and MgO tablet were passed through a feeding tube. We compared the yield of the molecular form of clopidogrel from each passed fraction.


</sec><sec>
<title>Results</title>
The substance obtained from the mixture of clopidogrel bisulfate tablet and sodium bicarbonate or MgO tablet was identified as the molecular form of clopidogrel, and chemical degradation did not occur under these conditions. In the tube passage test, the yield of clopidogrel (molecular form) from the mixture of clopidogrel bisulfate and MgO tablets was lower than that from the suspension of clopidogrel bisulfate tablet alone.


</sec><sec>
<title>Conclusions</title>
The mixture of clopidogrel bisulfate and MgO tablets caused a considerable reduction in the administered dose passed through the feeding tube. Therefore, it is recommended to administer the suspensions of clopidogrel bisulfate and MgO tablets separately for safe and effective pharmacotherapy.


</sec>

DOI： 10.1186/s40780-021-00202-1

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Other Link： https://link.springer.com/article/10.1186/s40780-021-00202-1/fulltext.html

Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acs.orglett.1c00840

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society ({ACS})  

DOI： 10.1021/jacs.0c08231

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society ({ACS})  

<jats:p>Here we interrogate the structurally dense (1.63 mcbits/Å&lt;sup&gt;3&lt;/sup&gt;) GABA&lt;sub&gt;A&lt;/sub&gt; receptor antagonist bilobalide, intermediates en route to its synthesis and related mechanistic questions. &lt;sup&gt;13&lt;/sup&gt;C isotope labeling identified an unexpected bromine migration en route to an α-selective, catalytic asymmetric Reformatsky reaction, ruling out an asymmetric allylation pathway. Experiment and computation converge on the driving forces behind two surprising observations. First, an oxetane acetal is shown to persist in concentrated mineral acid (1.5 M DCl in THF-d&lt;sub&gt;8&lt;/sub&gt;/D&lt;sub&gt;2&lt;/sub&gt;O), and its longevity is correlated to destabilizing steric clashes between substituents. Second, a regioselective oxidation of &lt;i&gt;des&lt;/i&gt;-hydroxybilobalide is found to rely on lactone acidification through lone-pair delocalization, which leads to extremely rapid intermolecular enolate equilibration. In addition, we describe multiple pitfalls, puzzles and unexpected reactions that ultimately uncovered a concise total synthesis. These problems arose from the high information density of bilobalide that distinguishes it from other scaffolds and may characterize natural product (NP) space more generally. Therefore, we also include a Python script to quickly (&lt;i&gt;ca.&lt;/i&gt; 132,000 molecules/ minute) calculate information content (Böttcher scores), which may be helpful to identify important features of NP space.</jats:p>

DOI： 10.26434/chemrxiv.12132939.v1

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Language：English   Publishing type：Research paper (scientific journal)  

© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: We postulate that the deoxyguanosine analogue CNDAG [9-(2-C-cyano-2-deoxy-1-β-d-arabino-pentofuranosyl)guanine] likely causes a single-strand break after incorporation into DNA, similar to the action of its cytosine congener CNDAC, and that subsequent DNA replication across the unrepaired nick would generate a double-strand break. This study aimed at identifying cellular responses and repair mechanisms for CNDAG prodrugs, 2-amino-9-(2-C-cyano-2-deoxy-1-β-d-arabino-pentofuranosyl)-6-methoxy purine (6-OMe) and 9-(2-C-cyano-2-deoxy-1-β-d-arabino-pentofuranosyl)-2,6-diaminopurine (6-NH2). Each compound is a substrate for adenosine deaminase, the action of which generates CNDAG. Methods: Growth inhibition assay, clonogenic survival assay, immunoblotting, and cytogenetic analyses (chromosomal aberrations and sister chromatid exchanges) were used to investigate the impact of CNDAG on cell lines. Results: The 6-NH2 derivative was selectively potent in T cell malignant cell lines. Both prodrugs caused increased phosphorylation of ATM and its downstream substrates Chk1, Chk2, SMC1, NBS1, and H2AX, indicating activation of ATM-dependent DNA damage response pathways. In contrast, there was no increase in phosphorylation of DNA-PKcs, which participates in repair of double-strand breaks by non-homologous end-joining. Deficiency in ATM, RAD51D, XRCC3, BRCA2, and XPF, but not DNA-PK or p53, conferred significant clonogenic sensitivity to CNDAG or the prodrugs. Moreover, hamster cells lacking XPF acquired remarkably more chromosomal aberrations after incubation for two cell cycle times with CNDAG 6-NH2, compared to the wild type. Furthermore, CNDAG 6-NH2 induced greater levels of sister chromatid exchanges in wild-type cells exposed for two cycles than those for one cycle, consistent with increased double-strand breaks after a second S phase. Conclusion: CNDAG-induced double-strand breaks are repaired mainly through homologous recombination.

DOI： 10.1007/s00280-020-04035-x

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41586-019-1690-5

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PubMed

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

The total synthesis of simpotentin (1), a new potentiator of amphotericin B activity against Candida albicans, was achieved. Our research results enabled the access of all stereoisomers of 1 and the elucidation of the unknown absolute configuration of 1. Furthermore, one of the stereoisomers is a better amphotericin B potentiator than 1 and is an excellent lead compound for the development of a novel amphotericin B potentiator.

DOI： 10.1021/acs.orglett.9b01945

PubMed

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.tetlet.2019.03.026

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.tet.2019.02.050

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.bcp.2018.06.022

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Ltd  

Currently, pyripyropene A, which is isolated from the culture broth of Aspergillus fumigatus FO-1289, is the only compound known to strongly and selectively inhibit the isozyme sterol O-acyltransferase 2 (SOAT2). To aid in the development of new cholesterol-lowering or anti-atherosclerotic agents, new A-ring simplified pyripyropene A analogues have been designed and synthesized based on total synthesis, and the results of structure–activity relationship studies of pyripyropene A. Among the analogues, two A-ring simplified pyripyropene A analogues exhibited equally efficient SOAT2 inhibitory activity to that of natural pyripyropene A. These new analogues are the most potent and selective SOAT2 inhibitors to be used as synthetic compounds and attractive seed compounds for the development of drug for dyslipidemia, including atherosclerotic disease and steatosis.

DOI： 10.1002/cmdc.201700645

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Other Link： http://orcid.org/0000-0001-7129-012X

Language：English   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Three new compounds, designated scopranones A-C, were isolated from the culture broth of a soil isolate, Streptomyces sp. BYK-11038, and shown to be inhibitors of bone morphogenetic protein (BMP) induced alkaline phosphatase activity in a BMP receptor mutant cell line. The structures were elucidated using NMR and other spectral data. The scopranones have an unusual structure with two atypical scooplike moieties linked at the tails to form part of a unique 3-furanone ring.

DOI： 10.1021/acs.orglett.7b03003

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

We applied a desilylation procedure using SO3H silica gel, with the surface modified by alkylsulfonic acid groups, to silylated sugar, nucleoside, and alkaloid derivatives. The treatment with SO3H silica gel provided desilylated products in good to excellent yield. In the reactions of sugar and nucleoside derivatives, no silyl residue was detected in the crude products, but the crude products of the reaction of alkaloids contained small amounts of silyl residues. Even though the sugar and nucleoside derivatives had a labile glycosyl and C-N bond, respectively, these bonds tolerated the reaction conditions. These outcomes suggested that the desilylation procedure using SO3H silica gel would be applicable to the deprotection of a variety of types of compounds protected by silyl groups. In a gram scale experiment, the desilylation procedure successfully proceeded without the observation of any silyl residue in the crude product. (C) 2017 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2017.07.047

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

11-O-Debenzoyltashironin (1) is a member of the neurotrophic sesquiterpenes, trace plant metabolites that enhance neurite outgrowth in cultured neurons. We report its synthesis in six steps from a butenolide heterodimer via its likely biosynthetic precursor, 3,6-dideoxy-10-hydroxypseudoanisatin, here identified as the chain tautomer of 1. Access to the tashironin chemotype fills a gap in a comparison set of convulsive and neurotrophic sesquiterpenes, which we hypothesized to share a common target. Here we show that both classes mutually hyperexcite rat cortical neurons, consistent with antagonism of inhibitory channels and a mechanism of depolarization-induced neurite outgrowth.

DOI： 10.1021/jacs.7b04206

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN ANTIBIOTICS RESEARCH ASSOC  

Nafuredin-gamma, obtained from natural nafuredin, has demonstrated a potent and selective inhibitory activity against nematode complex I. However, nafuredin-gamma is unstable in air since its conjugated dienes are oxygen-labile. The instability in air was naturally solved by the synthesis of structure-simplified nafuredin-gamma analogs without conjugated dienes. However, these modified analogs showed lower complex I inhibitory activities. Therefore, new air-stable structure-simplified nafuredin-gamma analogs were designed and synthesized herein. Among all analogs synthesized, the one bearing a unique 1-azabicyclo[3.1.0] hexane scaffold showed the highest inhibitory activity (IC50 = 170 nM) while presenting high selectivity against nematode complex I.

DOI： 10.1038/ja.2017.16

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：PHARMACEUTICAL SOC JAPAN  

Cyslabdan was isolated from the culture broth of Streptoinyces sp. K04-0144 as a new potentiator of imipenem activity against methicillin-resistant Staphylococcus aureus. We accomplished the synthesis of cyslabdan according to a previously reported structure. However, we subsequently found that this structure was incorrect; our analysis of natural cyslabdan showed that it possessed R stereochemistry at the C8 position, not S, as had previously been reported. Thus, we completed the protecting-group-free synthesis of the correct structure of cyslabdan, which is described herein.

DOI： 10.1248/cpb.c16-00382

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

The targets of antifungal antibiotics in clinical use are more limited than those of antibacterial antibiotics. Therefore, new antifungal antibiotics with different mechanisms of action are desired. In the course of our screening for antifungal antibiotics of microbial origins, new antifungal antibiotics, simplifungin (1) and valsafungins A (2) and B (3), were isolated from cultures of the fungal strains Simplicillium minatense FKI-4981 and Valsaceae sp. FKH-53, respectively. The structures of 1 to 3 including their absolute stereochemistries were elucidated using various spectral analyses including NMR and collision-induced dissociation (CID)-MS/MS as well as chemical approaches including modifications to the Mosher's method. They were structurally related to myriocin. They inhibited the growth of yeast-like and zygomycetous fungi with MICs ranging between 0.125 and 8.0 mu g/mL. An examination of their mechanisms of action by the newly established assay using LC-MS revealed that 1 and 2 inhibited serine palmitoyltransferase activity, which is involved in sphingolipid biosynthesis, with IC50 values of 224 and 24 nM, respectively.

DOI： 10.1021/acs.joc.6b00952

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS  

Sterol O-acyltransferase 2 (SOAT2; also known as ACAT2) is considered as a new therapeutic target for the treatment or prevention of hypercholesterolemia and atherosclerosis. Fungal pyripyropene A (PPPA: 1,7,11-triacyl type), the first SOAT2-selective inhibitor, proved orally active in vivo using atherogenic mouse models. The purpose of the present study was to demonstrate that the PPPA derivatives (PRDs) prove more effective in the mouse models than PPPA. Among 196 semisynthetic PPPA derivatives, potent, SOAT2-selective, and stable PRDs were selected. In vivo antiatherosclerotic activity of selected PRDs was tested in apolipoprotein E knockout (Apoe(-/-)) mice or low-density lipoprotein receptor knockout (Ldlr(-/-)) mice fed a cholesterol-enriched diet (0.2% cholesterol and 21% fat) for 12 weeks. During the PRD treatments, no detrimental side effects were observed. Among three PRDs, Apoe(-/-) mice treated with PRD125 (1-,11-O-benzylidene type) at 1 mg/kg/day had significantly lower total plasma cholesterol concentration by 57.9 +/- 9.3%; further, the ratio of cholesteryl oleate to cholesteryl linoleate in low-density lipoprotein was lower by 55.6 +/- 7.5%, respectively. The hepatic cholesteryl ester levels and SOAT2 activity in the small intestines and livers of the PRD-treated mice were selectively lowered. The atherosclerotic lesion areas in the aortae of PRD125-treated mice were significantly lower at 62.2 +/- 13.1%, respectively. Furthermore, both PRDs were also orally active in atherogenic Ldlr(-/-) mice. Among the PRDs tested, PRD125 was the most potent in both mouse models. These results suggest that SOAT2-selective inhibitors such as PRD125 have a high potential as poststatin agents for treatment and/or prevention in patients with atherosclerosis and hypercholesterolemia.

DOI： 10.1124/jpet.115.227348

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Nafuredin-gamma (2), converted from nafuredin (1) under mild basic conditions, demonstrates potent and selective inhibitory activity against helminth complex I. However, 2 is unstable in air because the conjugated dienes are oxygen-labile. To address this, we designed and synthesized air-stable nafuredin-gamma analogs. Although the complex I inhibitory activities of all the new nafuredin-gamma analogs were lower than that of 2, all were in the high nM range (IC50: 300-820 nM). (C) 2015 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmc.2015.01.030

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

5-(4'-Methoxyphenyl)-oxazole (MPO), originally reported as a synthetic compound, was isolated from fungal culture broth as an inhibitor of hatch and growth of Caenorhabditis elegans. Nineteen MPO derivatives were chemically synthesized, but showed no effect on C. elegans hatch and growth. These findings strongly suggested that the whole structure of MPO is essential for anti-C. elegans activity. (C) 2014 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmcl.2014.11.042

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN ANTIBIOTICS RESEARCH ASSOC  

Pyripyropene A (PPPA, 1) of fungal origin, a selective inhibitor of acyl-CoA: cholesterol acyltransferase 2 (ACAT2), proved orally active in atherogenic mouse models. The in vitro metabolites of 1 in liver microsomes and plasma of human, rabbit, rat and mouse were analyzed by ultra fast liquid chromatography and liquid chromatography/tandem mass spectrometry. In the liver microsomes from all species, successive hydrolysis occurred at the 1-O-acetyl residue, then at the 11-O-acetyl residue of 1, while the 7-O-acetyl residue was resistant to hydrolysis. Furthermore, dehydrogenation of the newly generated 11-alcoholic hydroxyl residue occurred in human and mouse-liver microsomes, while oxidation of the pyridine ring occurred in human and rabbit liver microsomes. On the other hand, hydrolysis of the 7-O-acetyl residue proceeded only in the mouse plasma. These data indicated that the in vitro metabolic profiles of 1 have subtle differences among animal species. All of the PPPA metabolites observed in liver microsomes and plasma markedly decreased ACAT2 inhibitory activity. These findings will help us to synthesize new PPPA derivatives more effective in in vivo study than 1.

DOI： 10.1038/ja.2014.91

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.5059/yukigoseikyokaishi.71.830

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

Here we report a novel and efficient method for the regioselective mono-deprotection of di-tert-butylsilylene acetals derived from 1,3-diols consisting of primary and secondary alcohols. The ammonium fluoride-mediated reactions of pyripyropene A derivative, thymidine and uridine derivatives, methyl beta-D-glucofuranoside, and pyranoside derivatives each gave the corresponding primary alcohol with high regioselectivity.

DOI： 10.1246/bcsj.20130237

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Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：SOC SYNTHETIC ORGANIC CHEM JPN  

Fungal pyripyropene A (PPPA, 1), consisting of pyridine, a-pyrone, and sesquiterpene moieties, is the only potent and selective inhibitor of acyl-CoA: cholesterol acyl transferase 2 (ACAT2) isozyme. In an effort to develop potent and selective inhibitors toward ACAT2, structure-activity relationship studies were carried out using derivatives based on 1. We have successfully developed novel 1,11-O-o-substituted benzylidene-7-p-cyanobenzoyloxy PPPA derivatives that exhibit significantly more potent ACAT2 inhibitory activity and much higher isozyme selectivity than 1.
Furthermore, we have achieved a stereocontrolled total synthesis of 1. Key features of the synthetic strategy included an intramolecular Ti (III)-mediated radical cyclization for construction of the A-ring, stereoselective beta-epoxide formation/Peterson olefination for preparation of the functional groups on the B-ring, and stereoselective intramolecular cyclization through hetero-Michael addition for C-ring formation. Extension of this chemistry to the synthesis of an A-ring truncated PPPA analog for structure-activity relationship studies has also been achieved.

DOI： 10.5059/yukigoseikyokaishi.71.830

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

In an effort to develop potent and selective inhibitors toward ACAT2, structure-activity relationship studies were carried out using derivatives based on pyripyropene A (PPPA, 1). In particular, we investigated the possibility of introducing appropriate 1,11-O-benzylidene and 7-O-substituted benzoyl moieties into PPPA (1). The new o-substituted benzylidene derivatives showed higher selectivity for ACAT2 than PPPA (1). Among them, 1,11-O-o-methylbenzylidene-7-O-p-cyanobenzoyl PPPA derivative 7q and 1,11-O-o, o-dimethylbenzylidene-7-O-p-cyanobenzoyl PPPA derivative 7z proved to be potent ACAT2 inhibitors with unprecedented high isozyme selectivity. (C) 2013 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmcl.2013.04.075

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Synthesis and structure-activity relationships of 7-O-p-cyanobenzoyl pyripyropene A derivatives with modification at C1 and 11 are described. Regioselective mono-deprotection of di-tert-butylsilylene acetal was critical in their synthesis. (C) 2013 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmcl.2013.02.088

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

In an effort to develop potent and selective inhibitors toward ACAT2, structure-activity relationship studies were carried out using derivatives based on pyripyropene A (PPPA, 1). We have successfully developed novel PPPA derivatives with a 7-O-substituted benzoyl substituent that significantly exhibit more potent ACAT2 inhibitory activity and higher ACAT2 isozyme selectivity than 1. (c) 2013 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmcl.2012.12.099

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Publishing type：Research paper (scientific journal)   Publisher：Wiley-Blackwell  

DOI： 10.1002/chin.201247212

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：PHARMACEUTICAL SOC JAPAN  

The stereoselective total synthesis of atpenins A4 (2) and B (3), harzianopyridone (4), and NBRI23477 B (5) have been developed using a convergent approach involving the coupling reaction of a common iodopyridine with an aldehyde corresponding to the appropriate side chain of the desired compound. Furthermore, the absolute configurations of atpenin B (3), harzianopyridone (4), and NBRI23477 B (5) have been unambiguously determined.

DOI： 10.1248/cpb.c12-00266

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PHARMACEUTICAL SOC JAPAN  

Most cancer cells have mutations in genes at the Cl checkpoint and repair DNA only in the 62 phase; therefore, the 62 checkpoint is a potential target to develop novel therapy. In the course of screening, a known compound, pycnidione, was isolated from the fungal culture broth of Gloeotinia sp. FKI-3416. Pycnidione irreversibly abrogated bleomycin-induced G2 arrest in Jurkat cells and synergically potentiated the cytotoxicity of bleomycin. To elucidate the mechanism of action, the effect of pycnidione on the signal transduction of the 62 checkpoint was analyzed, showing that the increased phospho-cyclin dependent kinase-1 (CDK1) level caused by bleomycin was abrogated in the presence of pycnidione, indicating that cells did not arrest at the 62 phase. Moreover, under these conditions, Chk1 and Chk2 levels were markedly down-regulated. Thus, we concluded that pycnidione abrogated bleomycin-induced 62 arrest by decreasing Chk1 and Chk2.

DOI： 10.1248/bpb.35.18

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The total synthesis of pyripyropene A, a potent ACAT2 inhibitor with high isozyme selectivity, was completed. Key features of the synthetic strategy include Ti(III)-mediated radical cyclization and Peterson olefination for the construction of the AB ring segment and stereoselective dihydro-gamma-pyrone formation (C-ring). The total synthesis provided pyripyropene A in 5.3% overall yield over 17 steps. (C) 2011 Published by Elsevier Ltd.

DOI： 10.1016/j.tet.2011.06.084

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Publishing type：Research paper (scientific journal)   Publisher：Wiley-Blackwell  

DOI： 10.1002/chin.200945203

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN ANTIBIOTICS RESEARCH ASSOC  

Enantioselective total synthesis of atpenin A5, a potent mitochondrial complex II (succinate-ubiquinone oxidoreductase) inhibitor, has been achieved by a convergent approach through a coupling reaction between 5-iodo-2,3,4,6-tetraalkoxypyridine and a side-chain aldehyde. The two key segments were synthesized through ortho-metalation/boronation with (MeO)(3)B/oxidation with mCPBA, ortho-iodination, halogen dance reaction, Sharpless epoxidation and regioselective epoxide-opening reaction. This synthetic study resulted in the revision of the earlier reported (1)H-NMR data of the natural atpenin A5 and the confirmation of the stereochemical assignment. The Journal of Antibiotics (2009) 62, 289-294; doi:10.1038/ja.2009.29; published online 17 April 2009

DOI： 10.1038/ja.2009.29

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Several 9-(2-C-cyano-2-deoxy-l-beta-D-arabino-pentofuranosyl)purine derivatives were tested against Kaposi's sarcoma-associated herpesvirus (KSHV)-infected primary effusion lymphoma (PEL) cells. The guanine derivative (2, CNDAG) as well as the 2-amino-6-substituted-purine derivatives 3, 4 and 5 inhibited KSHV-positive cell growth but showed no cytotoxicity against KSHV-negative cells at >15 muM concentrations. Therefore, it was found that compounds 2, 3, 4 and 5 showed selective cytotoxicity against PEL cells infected with KSHV.

DOI： 10.1093/nass/nrp048

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN ANTIBIOTICS RESEARCH ASSOC  

Selectivity of 96 semisynthetic derivatives prepared from fungal pyripyropene A, originally isolated as a potent inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), toward ACAT1 and ACAT2 isozymes was investigated in the cell-based assay using ACAT1- and ACAT2-expressing CHO cells. Eighteen derivatives including PR-71 (7-O-isocaproyl derivative) showed much more potent ACAT2 inhibition (IC(50): 6.0 to 62 nM) than pyripyropene A (IC(50): 70 nM). Among them, however, natural pyripyropene A showed the highest selectivity toward ACAT2 with a selectivity index (SI) of &gt;1000, followed by PR-71 (SI, 667).

DOI： 10.1038/ja.2008.67

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Nafuredin (1) is converted to nafuredin-gamma (2) under mild basic conditions and both compounds exhibit the same inhibitory activity and selectivity against NADH-fumarate reductase (complex 1). The total synthesis of 2 was achieved by a convergent approach using Stille coupling. The structural elements required for inhibitory activity against NADH-fumarate reductase (complex I) were then investigated by evaluation of nafuredin-gamma (2) and its structural analogues. (C) 2008 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2008.06.066

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Several 9-(2-C-cyano-2-deoxy-l-beta-D-arabino-pentofuranosyl)purine derivatives were tested against Kaposi's sarcoma-associated herpesvirus (KSHV)-infected primary effusion lymphoma (PEL) cells. The guanine derivative (3, CNDAG), as well as the 2-amino-6-substituted-purine derivatives 4, 5, and 6, exhibited cell growth inhibitory activity against KSHV-infected cells, but showed no cytotoxicity against KSHV-negative cells at &gt; 15 mu M concentrations. Therefore, it was found that compounds 3, 4, 5, and 6 showed selective cytotoxicity against PEL cells infected with KSHV.

DOI： 10.1021/jm070032y

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Event date： 20 11 2023 - 23 11 2023

Language：English   Presentation type：Poster presentation  

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Presentation type：Oral presentation (invited, special)  

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Event date： 26 5 2023 - 27 5 2023

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Presentation type：Poster presentation  

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Language：Japanese   Presentation type：Poster presentation  

Venue：京都  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：京都  

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Language：Japanese   Presentation type：Poster presentation  

Venue：京都  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：岡山  

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Language：Japanese   Presentation type：Poster presentation  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：広島  

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Language：English   Presentation type：Oral presentation (general)  

Venue：San Diego, USA  

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Language：English   Presentation type：Poster presentation  

Venue：San Diego, USA  

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Language：English   Presentation type：Poster presentation  

Venue：San Diego, USA  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Oral presentation (keynote)  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：熊本  

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Language：Japanese   Presentation type：Poster presentation  

Venue：久留米  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京 帝京平成大学中野キャンパス  

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Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

Venue：東京  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪  

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Language：Japanese   Presentation type：Poster presentation  

Venue：金沢  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：金沢  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：相模原  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：相模原  

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Language：Japanese   Presentation type：Poster presentation  

Venue：相模原  

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Language：Japanese   Presentation type：Poster presentation  

Venue：名古屋  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：仙台  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：茨城  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：横浜  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：English   Presentation type：Poster presentation  

Venue：ホノルル  

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Language：Japanese   Presentation type：Poster presentation  

Venue：千葉県  

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Language：English   Presentation type：Poster presentation  

Venue：京都  

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Language：Japanese   Presentation type：Poster presentation  

Venue：大阪  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：神戸  

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Language：Japanese   Presentation type：Poster presentation  

Venue：神戸  

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Language：Japanese   Presentation type：Poster presentation  

Venue：神戸  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：神戸  

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Language：Japanese   Presentation type：Oral presentation (invited, special)  

Venue：神戸  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京都町田市  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京都町田市  

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Language：Japanese   Presentation type：Poster presentation  

Venue：熊本  

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Language：Japanese   Presentation type：Poster presentation  

Venue：熊本  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：神奈川  

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Language：Japanese   Presentation type：Poster presentation  

Venue：神奈川  

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Language：Japanese   Presentation type：Poster presentation  

Venue：神奈川  

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Language：Japanese   Presentation type：Poster presentation  

Venue：広島  

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Language：Japanese   Presentation type：Poster presentation  

Venue：広島  

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Language：Japanese   Presentation type：Poster presentation  

Venue：広島  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Poster presentation  

第30回白金シンポジウム講演要旨集 p.6

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Language：Japanese   Presentation type：Poster presentation  

第30回白金シンポジウム講演要旨集 p.7

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Language：English   Presentation type：Poster presentation  

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Language：Japanese   Presentation type：Poster presentation  

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Language：Japanese   Presentation type：Poster presentation  

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Language：English   Presentation type：Poster presentation  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：札幌  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：札幌  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Language：English   Presentation type：Poster presentation  

Venue：Tokyo  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：千葉  

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Language：Japanese   Presentation type：Poster presentation  

Venue：大阪  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Poster presentation  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Poster presentation  

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Language：Japanese  

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Language：Japanese  

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Language：Japanese  

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Language：Japanese  

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Language：Japanese  

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Language：Japanese  

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Language：Japanese  

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Language：Japanese  

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Language：Japanese  

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Language：Japanese  

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Language：Japanese  

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Language：Japanese  

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Language：Japanese  

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Applicant：学校法人北里研究所

Application no：特願2013-012868  Date applied：28 1 2013

Announcement no：特開2014-144922  Date announced：14 8 2014

J-GLOBAL

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Applicant：学校法人北里研究所

Application no：JP2011057336  Date applied：25 3 2011

Announcement no：WO2011-122468  Date announced：6 10 2011

J-GLOBAL

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Applicant：学校法人北里研究所

Application no：特願2012-508258  Date applied：25 3 2011

Patent/Registration no：特許第5592482号  Date issued：8 8 2014

J-GLOBAL

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Applicant：学校法人北里研究所

Application no：JP2010060461  Date applied：21 6 2010

Announcement no：WO2010-150739  Date announced：29 12 2010

J-GLOBAL

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Applicant：学校法人北里研究所

Application no：特願2011-519884  Date applied：21 6 2010

Patent/Registration no：特許第5554330号  Date issued：6 6 2014

J-GLOBAL

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