METHOD FOR PRODUCING OPTICALLY ACTIVE 2, 3-BISPHOSPHINOPYRAZINE DERIVATIVE AND METHOD FOR PRODUCING OPTICALLY ACTIVE PHOSPHINE TRANSITION METAL COMPLEX
申请人:NIPPON CHEMICAL INDUSTRIAL CO., LTD.
公开号:US20200087330A1
公开(公告)日:2020-03-19
In the method for producing an optically active 2,3-bisphosphinopyrazine derivative of the present invention, an optically active 2,3-bisphosphinopyrazine derivative represented by the following formula (3) is produced by the step of: preparing solution A containing 2,3-dihalogenopyrazine represented by the following formula (1)
and a carboxylic acid amide coordinating solvent, lithiating an optically active R- or S-isomer of a hydrogen-phosphine borane compound represented by the following formula (2)
to give a lithiated phosphine borane compound; adding solution B containing the lithiated phosphine borane compound to the solution A to perform an aromatic nucleophilic substitution reaction; and then performing a deboranation reaction.
(For symbols in the formulas, see the description.)
We found that Au(I) complexed with 2,3-bis(tert-butyl(methyl)phosphino) quinoxaline (10) was a potent anti-tumor agent (half-maximal growth inhibitory concentration, GI50 = 0.87 μM) with broad anti-tumor activity. In particular, the activity of complex 10 was high in tumor cell lines derived from the colon and ovary. Treatment with complex 10 resulted in the apoptosis of HL-60 cells. The ligand for