Shunsuke Sueki

A one-shot substitution of all hydrogens at the α,β-positions of saturated cyclic amines was achieved. The key feature of this reaction is the sequential involvement of intra- and intermolecular redox processes. When N,O-acetals obtained through an internal redox process were treated with a catalytic amount of Zn(OTf)2 and an excess amount of benzylidene barbiturates, three key transformations involving intermolecular redox process occurred successively to afford α,β-unsaturated lactams in moderate to good chemical yields.

<jats:title>Abstract</jats:title><jats:p>Ependymomas are rare and chemotherapy-resistant gliomas. One subclass of supratentorial ependymomas, ST-EPN-ZFTA, expresses a fusion protein consisting of a nuclear protein, zinc finger translocation associated (ZFTA), and<jats:italic>v-rel</jats:italic>reticuloendotheliosis viral oncogene homolog A (RELA), an effector transcription factor of the nuclear factor-κB (NF-κB) pathway (ZFTA-RELA). Constitutive localization of ZFTA-RELA to the nucleus hyperactivates the oncogenic NF-κB signaling pathway, thereby contributing to the pathogenesis of ST-EPN-ZFTA. To identify compounds that inhibit NF-κB activity induced by ZFTA-RELA, we established a high-throughput screening system using the NF-κB-responsive luciferase reporter cell line 6E8, which expresses ZFTA-RELA in a doxycycline-dependent manner. A chemical library of 9600 compounds selected for their structural diversity was screened, and a colchicine derivative was identified. Among colchicine and six of its derivatives, the IC<jats:sub>50</jats:sub>on ZFTA-RELA-dependent NF-κB-responsive luciferase activity in 6E8 cells was found to be the lowest for colchicine at 90 nM. Interestingly, microtubule polymerization inhibitors (colchicine and vinblastine) and dynein inhibitors (ciliobrevin D and dynarrestin) impaired ZFTA-RELA’s nuclear localization and NF-κB activity in 6E8 cells. These findings indicate that microtubule polymerization and dynein play pivotal roles in activating the NF-κB pathway in ST-EPN-ZFTA by promoting the nuclear localization of ZFTA-RELA. Consequently, inhibition of microtubule polymerization may be a therapeutic strategy for ST-EPN-ZFTA.</jats:p>

The new chalcogenylation of phosphines using nBu4N‧XCN (X=S, Se) is described. The reaction in 1,2-dichloroethane at 120°C provided the corresponding phosphine sulfides in good to high yields. The protocol could be extended to the synthesis of phosphinic acid derivatives as well as sulfurization of poly(styrene-co-4-styryldiphenylphosphine).

A concise and direct cyanation of secondary and tertiary benzylic and allylic alcohols catalyzed by Brønsted acid has been developed using trimethylsilyl cyanide (TMSCN) as a cyanide source and 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP) as a solvent. The present transition metal‐free catalytic process is operationally simple to perform under “open‐flask” conditions and it is applicable to the preparation of a number of α‐arylacetonitriles as well as late‐stage material transformations. The effectiveness of the present protocol was further demonstrated by the first enantioselective synthesis and determination of the absolute configuration of verimol F.