Kiyoshi Tanaka

Domino Heck–C–H activation reaction of unsymmetrically substituted [3]cumulene

The Heck reaction of an unsymmetrically substituted [3]cumulene has been investigated. Although a carbonyl conjugated alkene is present, the arylpalladium species selectively inserts into the C3-4 double bond, and a subsequent C-H activation reaction with a neighboring phenyl group gives the indene derivatives with a tetrasubstituted olefin moiety.

Inhibition of human parainfluenza virus type 1 sialidase by analogs of 2-deoxy-2,3-didehydro- N-acetylneuraminic acid

Eleven novel analogs of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en) modified at the C-4 and C-9 positions were designed and tested for their ability to inhibit sialidase of human parainfluenza virus type 1 (hPIV-1). The analogs modified by the cyanomethyl, amidinomethyl, and thiocarbamoylmethyl groups at the C-4 position exhibited potent inhibition against hPIV-1 sialidase compared with Neu5Ac2en. The most effective compound was thiocarbamoylmethyl analog (4-O-thiocarbamoylmethyl-Neu5Ac2en). The activity of 4-O-thiocarbamoylmethyl-Neu5Ac2en causing 50% enzyme inhibition at a concentration of approximately 1.0×10−5M was 30-fold larger than Neu5Ac2en. While, the analogs of Neu5Ac2en modified by the azido and N-acetyl groups at the C-9 showed a decrease in inhibition of sialidase compared with the 9-hydroxy analogs. In addition, 4-O-thiocarbamoylmethyl-Neu5Ac2en strongly inhibited hPIV-1 infections of Lewis lung carcinoma-monkey kidney cells in comparison with Neu5Ac2en. The present findings would provide useful information for the development of anti-human parainfluenza virus compounds.

Enantioselective synthesis of allenecarboxylates from phenyl acetates through CC bond forming reactions

Abstract A variety of optically active 4,4-disubstituted allenecarboxylic acid methyl esters were prepared from simple α,α-disubstituted phenyl acetate through base treatment of the esters to generate ketenes, followed by successive Horner–Wadsworth–Emmons reaction. The transformation was further developed as a one-pot procedure with satisfactory yields and high enantioselectivity.

Identification of a small-molecule inhibitor of the interaction between Survivin and Smac/DIABLO

The protein Survivin is selectively overexpressed in a variety of cancers, but not in normal tissues. It has been reported to be involved in cell survival and cell division. However, the molecular mechanisms involved in its function are not clear, although several binding partner proteins have been proposed to date. Here, we report the identification of a novel small molecule Survivin antagonist, which disrupts the Survivin-Smac/DIABLO interaction in cells. In order to identify Survivin-directed antagonists, we developed a high-throughput screening system based on AlphaScreen technology, which allows the identification of small molecules with the ability to inhibit the interaction of Survivin with Smac/DIABLO or INCENP in vitro. We screened chemical libraries, generated in-house, using this system and identified a 5-deazaflavin analog (compound 1) as a hit compound that selectively inhibited the interaction of Survivin with Smac/DIABLO but not INCENP. In cultured cells, compound 1 abrogated the formation of the complex between Survivin and Smac/DIABLO. In addition, this compound was able to sensitize cultured cells to doxorubicin-mediated DNA damage stress and synergistically enhance apoptotic cell death. Thus, the small-molecule inhibitor described here may serve as a proof-of-principle agent for discriminating between the multiple functions of Survivin.

Synthesis of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid analogues modified at the C-4 and C-9 positions and their behaviour towards sialidase from influenza virus and pig liver membrane

The synthesis of novel 2-deoxy-2,3-didehydro-N-acetylneuraminic acid analogues structurally varied at C-4 and C-9 by transformation from versatile key intermediates and their inhibitory activity against sialidase from influenza virus A and pig liver membrane are described.

Glycosylation of sialyl acetates with a novel catalyst combination: Bismuth triflate and BF3·OEt2 system

A combined system of bismuth triflate [Bi(OTf)(3)] and boron trifluoride etherate (BF(3).OEt(2)) in dichloromethane is an efficient promoter for the glycosylation of N-acetylneuraminic acid derivatives. The co-existence of two acid catalysts such as Bi(OTf)(3)-BF(3).OEt(2) or Bi(OTf)(3)-PPA is confirmed to be essential for obtaining high yields of glycosylation products with p-nitrobenzyl alcohol, which also turned to be superior to those reported previously.

Enantioselective oxidative coupling of 2-naphthol derivatives catalyzed by Camellia sinensis cell culture

Optically active 1,1′-binaphthyl-2,2′-diols were synthesized by oxidative coupling of 2-naphthols using Camellia sinensis cell culture as a catalytic system.

Asymmetric olefination of metallic arene or diene complexes to form planar chiral complexes

Abstract The chiral phosphonoacetate ( S )- 1 can discriminate between the enantiotopic dicarbonyls of η 6 -arene Cr and η 4 -diene Fe complexes to afford optically active olefins with planar chirality in high enantiomeric excess and good yield. An analogous reagent ( S )- 2 was used for kinetic resolution of a racemic mixture of the aldehyde of the Fe η 4 -diene, which resulted in formation of the corresponding olefin together with the recovered aldehyde in high enantiomeric excess. The absolute stereostructures of these adducts were determined by X-ray analysis with anomalous dispersion of metals.

Use of Phenyl 2-α-Selenoglycosides of N-Acetylneuraminic Acid as a Glycosyl Donor for the Glycosylation Reactions

Phenyl 2-alpha-selenoglycosides of Neu5Ac were successfully prepared from the corresponding peracetylated chloro derivative of Neu5Ac 1 and phenylselenol in the presence of N,N-di-isopropylethylamine in excellent yields. The reaction of with various alcohols was effectively catalyzed by NIS/TfOH or DMTST to produce a variety of glycosides in moderate yields. Selective activation of over phenyl 2-alpha-thioglycoside of Neu5Ac with AgOTf/K(2)CO(3) was also achieved.

Synthesis of optically active α-phenylpyridylmethanols by Camellia sinensis cell culture

(S)-(+)-α-phenyl-2-pyridylmethanol has analgetic and anticonvul sant activities; however, effective asymmetric synthesis by chemical or biological means has not been reported. We developed a method for producing (S)-(+)-α-phenyl-2-pyridylmethanol in 83% chemical yield with 86% optical yield by the repetitive use of immobilized Camellia sinensis cell culture. The C. sinensis cell culture showed similar capability for asymmetric bioreduction to that of Catharanthus roseus cell culture.