Biomedical subjects
Publications and source records attributed to Kyoko Nozaki.
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Nucleophilic, anionic boryl compounds are long-sought but elusive species. We report that reductive cleavage of the boron-bromine bond in N,N'-bis(2,6-diisopropylphenyl)-2-bromo-2,3-dihydro-1H-1,3,2-diazaborole by lithium naphthalenide afforded the corresponding boryllithium, which is isoelectronic with an N-heterocyclic carbene. The structure of the boryllithium determined by x-ray crystallography was consistent with sp(2) boron hybridization and revealed a boron-lithium bond length of 2.291 +/- 0.006 angstroms. The structural similarity between this compound and the calculated free boryl anion suggests that the boron atom has an anionic charge. The (11)B nuclear magnetic resonance spectrum also supports the boryl anion character. Moreover, the compound behaves as an efficient base and nucleophile in its reactions with electrophiles such as water, methyl trifluoromethanesulfonate, 1-chlorobutane, and benzaldehyde.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology. Tyrosine phosphorylation and protein expression of the T-cell receptor zeta chain (zeta) have been reported to be significantly decreased in SLE T cells. In addition, zeta mRNA with alternatively spliced 3' untranslated region (zetamRNA/as-3'UTR) is detected predominantly in SLE T cells, and aberrant zeta mRNA accompanied by the mutations in the open reading frame including zeta mRNA lacking exon7 (zetamRNA/exon7-) is observed in SLE T cells. These zeta mRNA splice variant forms exhibit a reduction in the expression of TCR/CD3 complex and zeta protein on their cell surface due to the instability of zeta mRNA splice variant forms as well as the reduction in interleukin (IL)-2 production after stimulating with anti-CD3 antibody. Data from cDNA microarray showed that 36 genes encoding cytokines and chemokines, including IL-2, IL-15, IL-18, and TGF-beta2, were down-regulated in the MA5.8 cells transfected with the zeta mRNA splice variant forms. Another 16 genes were up-regulated and included genes associated with membranous proteins and cell damage granules, including the genes encoding poliovirus-receptor-related 2, syndecan-1, and granzyme A.
Highly fluorinated epoxides were polymerized under mild conditions regioregularly, which gave easy access to isotactic polymers by using optically pure epoxides.
The palladium-catalyzed alternating copolymerization of fluoroalkenes, represented as CH(2)=CH-CH(2)-C(n)F(2n+1), with CO was performed using (R,S)-BINAPHOS (2e) as a ligand. The CH(2)-C(n)F(2n+1) group is the most electronegative substituent ever reported for the copolymerization (Taft's sigma value of 0.90 for CH(2)CF(3)). The copolymer obtained from CH(2)=CH-CH(2)-C(8)F(17) (1a) existed as a mixture of polyspiroketal and polyketone, while that from CH(2)=CH-CH(2)-C(4)F(9) (1b) was a pure polyspiroketal, as was revealed by infrared and (13)C-CP/MAS NMR spectroscopies. The terminal structure of the polymer from 1b was confirmed by MALDI-TOF MS spectrometry. Detailed NMR studies suggested that the much higher reactivity with (R,S)-BINAPHOS (2e) than that with the conventional ligand DPPP (2a) can be attributed to the unique 1,2-insertion of the fluoroalkene into acylpalladium species. The existence of an electronegative substituent on the alpha-carbon of the palladium center is successfully avoided in the 1,2-insertion mechanism.
We have reported that the TCRzeta mRNA with alternatively spliced 3' UTR (zeta mRNA/as-3'-untranslated region (UTR)) and zeta mRNA lacking exon 7 (zeta mRNA/exon 7-) observed in systemic lupus erythematosus patient T cells can lead to down-regulation of both zeta and TCR/CD3 complexes. To determine whether these T cells expressing decreased zeta exhibit differential transcription patterns, we transfected retrovirus vectors containing wild-type zeta cDNA, zeta cDNA/as-3' UTR, and zeta cDNA/exon 7- into murine T cell hybridoma MA5.8 cells which lack zeta expression to construct the MA5.8 mutants WT, AS3' UTR, and EX7-, respectively. FACS analyses demonstrated reduced cell surface expression of zeta and TCR/CD3 complexes on the AS3' UTR mutant and the EX7- mutant in comparison to that on the WT mutant. Total RNA was collected after stimulating the MA5.8 mutants with anti-CD3 Ab. Reverse-transcribed cDNA was applied to the mouse cDNA microarray containing 8691 genes, and the results were confirmed by real-time PCR. The results showed that 36 genes encoding cytokines and chemokines, including IL-2, IL-15, IL-18, and TGF-beta2, were down-regulated in both the AS3' UTR mutant and the EX7- mutant. Another 16 genes were up-regulated in both, and included genes associated with membranous proteins and cell damage granules, including the genes encoding poliovirus receptor-related 2, syndecan-1, and granzyme A. Increased protein expression of these genes was confirmed by Western blot and FACS analyses. Identification of these responsive genes in T cells in which the zeta and TCR/CD3 complexes were down-regulated may help to better understand the pathogenesis of systemic lupus erythematosus.
Reaction of diarylphosphinobenzene-2-sulfonic acids with tertially amines, followed by addition of [PdMeCl(cod)], provided anionic methylpalladium(II) complexes with bidentate phosphine-sulfonate ligands, which show high activity for copolymerization of ethylene with methyl acrylate.
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The integrin alpha(E)beta(7) is expressed on intestinal intraepithelial T lymphocytes and CD8(+) T lymphocytes in inflammatory lesions near epithelial cells. Adhesion between alpha(E)beta(7)(+) T and epithelial cells is mediated by the adhesive interaction of alpha(E)beta(7) and E-cadherin; this interaction plays a key role in the damage of target epithelia. To explore the structure-function relationship of the heterophilic adhesive interaction between E-cadherin and alpha(E)beta(7), we performed cell aggregation assays using L cells transfected with an extracellular domain-deletion mutant of E-cadherin. In homophilic adhesion assays, L cells transfected with wild-type or a domain 5-deficient mutant formed aggregates, whereas transfectants with domain 1-, 2-, 3-, or 4-deficient mutants did not. These results indicate that not only domain 1, but domains 2, 3, and 4 are involved in homophilic adhesion. When alpha(E)beta(7)(+) K562 cells were incubated with L cells expressing the wild type, 23% of the resulting cell aggregates consisted of alpha(E)beta(7)(+) K562 cells. In contrast, the binding of alpha(E)beta(7)(+) K562 cells to L cells expressing a domain 5-deficient mutant was significantly decreased, with alpha(E)beta(7)(+) K562 cells accounting for only 4% of the cell aggregates, while homophilic adhesion was completely preserved. These results suggest that domain 5 is involved in heterophilic adhesion with alpha(E)beta(7), but not in homophilic adhesion, leading to the hypothesis that the fifth domain of E-cadherin may play a critical role in the regulation of heterophilic adhesion to alpha(E)beta(7) and may be a potential target for treatments altering the adhesion of alpha(E)beta(7)(+) T cells to epithelial cells in inflammatory epithelial diseases.
Asymmetric amplification in the copolymerization of cyclohexene oxide and carbon dioxide was demonstrated using chiral zinc complexes, prepared from diethylzinc, diphenyl(pyrrolidin-2-yl)methanol, and ethanol.
The double N-arylation of primary amines with 2,2'-biphenylylene ditriflates was investigated for the synthesis of multisubstituted carbazoles. Palladium complexes supported by 2-dicyclohexylphosphino-2'-methylbiphenyl or Xantphos [4,5-bis(diphenylphosphino)-9,9-dimethylxanthene] were found to be efficient catalysts for the reaction. The catalysts allow the use of anilines with an electron-donating or electron-withdrawing substituent and multisubstituted 2,2'-biphenylylene ditriflates as substrates. Ammonia equivalents, such as O-tert-butyl carbamate, are also employable as a nitrogen source to give the N-protected carbazoles which can easily give the corresponding N-unsubstituted carbazoles after deprotection. By using this methodology, a carbazole alkaloid, mukonine, is synthesized in 40% yield for five steps, in comparable efficiency to the recent precedents.
Characteristic features of unsymmetric bidentate ligands, in which the two coordination atoms are not equivalent, are reviewed with a focus on their use in metal-catalyzed olefin carbonylations. High enantioselectivity for a variety of substrates was achieved using ligand 9 in Rh-catalyzed hydroformylation. Unsymmetric ligand 21e shows high productivity accompanied by high regio- and enantioselectivities in the Pd-catalyzed alternating copolymerization of 1-alkene with CO. The advantages of electronic unsymmetry are demonstrated especially in the spectroscopic observation of single steps involved in catalytic cycles.
[reaction: see text] A simultaneous hydroxylation-carboxylation of biphenyl occurred to give 4'-hydroxy-4-biphenylcarboxylic acid, which has wide potential application as a polyester monomer.
Using an (R,S)-BINAPHOS-Rh(I) catalyst that is covalently anchored to a highly cross-linked polystyrene support, asymmetric hydroformylation of olefins was performed in the absence of organic solvents. The reaction of cis-2-butene, a gaseous substrate, provided (S)-2-methylbutanal with 100% regioselectivity and 82% ee upon treatment with H(2) (12 atm) and CO (12 atm) in a batchwise reactor equipped with a fixed bed. The polymer-supported catalyst was applicable to a continuous vapor-flow column reactor, and thus, 3,3,3-trifluoropropene was converted into (S)-2-trifluoromethylpropanal with an iso/normal ratio of 95/5 and 90% ee. Less volatile olefins, such as styrene, vinyl acetate, 1-alkenes, and fluorinated alkenes, were successfully converted into the corresponding isoaldehydes with high ee values, when they were injected through a supercritical CO(2)-flow column reactor. Successive injection of a series of olefins realized the conversion of an olefin library into an optically active aldehyde library.
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Dimeric zinc complex 2a [ = Et(2)Zn(2)(1a)(2)] has been synthesized by the reaction of Et(2)Zn and (S)-diphenyl(pyrrolidin-2-yl)methanol (1a-H). X-ray crystallography revealed that the alkoxide ligand replaced one of the two ethyl groups of Et(2)Zn and formed a five-membered chelate ring through a Zn-N dative bond. Two zinc centers were bridged by oxygen atoms to form a Zn(2)O(2) four-membered ring with a syn relationship between the two ethyl groups on the zinc centers. Dimeric zinc complex 2a was an active catalyst for asymmetric alternating copolymerization of cyclohexene oxide and CO(2). An MALDI-TOF mass spectrum of the obtained copolymer showed that the copolymerization was initiated by the insertion of CO(2) into Zn-alkoxide to give [(S)-diphenyl(pyrroridin-2-ly)methoxy]-[C(=O)O-(1,2-cyclohexylene)-O](n)-H (copolymer I), including chiral ligand 1a as an initiating group. Complex 3a-OEt ( = EtZn(1a)(2)ZnOEt), in which an ethoxy group replaced one of the two ethyl groups in 2a, also polymerized cyclohexene oxide and CO(2) with higher catalytic activity and enantioselectivity than 2a and afforded EtO-[C(=O)O-(1,2-cyclohexylene)-O](n)-H ( = copolymer III), including an ethoxy group as an initiating group. Throughout the studies, dimeric zinc species are indicated to be the active species for the copolymerization. It is also depicted that the substituent on the aryl moiety in diaryl(pyrrolidin-2-yl)methanol 2b-e influenced the polymerization activity.
[reaction: see text] Palladium-catalyzed coupling reaction of N,N-dimethylformamide with aryl or alkenyl halides successfully proceeded in the presence of phosphoryl chloride to afford the corresponding tertiary amides in good yields.
A new class of polymer-supported (R,S)-BINAPHOS 1e in which the parent BINAPHOS has two alkoxy-substituents at the 3-positions of the phenyls, has been synthesised. Using its Rh(I) complex, asymmetric hydroformylation of olefins proceeded with higher enantioselectivity in some cases compared to the conventional polymer-supported 1c.