|Budget Amount *help
¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1997 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1996 : ¥1,800,000 (Direct Cost : ¥1,800,000)
Nicotinamide-adenine dinucleotide (NAD) is an important coenzyme involved in many oxidation and reduction reactions in biological system. Parapyridinophane derivatives having planar chirality was designed as model compounds of the coenzyme to investigate a highly stereoselective organic reactions. A synthesis and optical resolution of the pyridinophane and its use in asymmetric reduction of ethyl benzoylformate was examined in this study.
The synthesis of a parapyridinophane derivative, 8-ethoxycarbonylparacyclol (2,5)-pyridinophane, was started from a coupling reaction of 2,5-bis (bromomethyl)-3-ethoxy-carbonylpyridine and 1,4-bis-(mercaptomethyl) benzene. The corresponding dithiaphane was obtained in 51% yield and it was then oxidized to the corresponding disulfone in 94% yield with m-chloroperbanzoic acid. The flash vacuum pyrolysis of the disulfone afforded the desired parapyridinophane derivative in 53% yield after detailed study of the reaction conditions of the pyrolysis. T
hen the pyndinophane derivative was subjected to optical resolution and it was found that the resolution was achieved by HPLC using a chiral column to afford the desired optically active parapyridinophane, It was also separated as diastereomers after converting to amide with chiral 1-phenylethylamine. The parapyridinophanes were then derived to the coresponding dihydropyridine derivatives by N-methylation with methyl iodide followed by reduction with sodium dithionite. Reduction of ethyl benzoylformate was examined by using these dihydropyridine derivatives. However, the reaction did not proceeded and the starting material was recovered. To examine the reason that the reaction did not take place, a synthesis of another dihydropyridinophane with less strained structure was carried out. 8-Ethoxycarbonyl  paracyclo  (2,5)-pyridinophane was obtained in racemic form by using the similar reaction scheme. The optical resoluton and derivatization to the corresponding dihydropyridine derivative will be examined in due course.
Although the asymmetric reduction of ethyl benzoylformate has not yet been realized using NADH model compounds of parapyridinophane, the synthetic route for para-pyridinophane derivative was established by this study. The synthetic utility of these compounds will be reported in the future. Less