Saichi Matsumoto

Synthesis and activities of oxidative metabolites of the anti-arthritic drug candidate S-2474

We have synthesized and characterized some oxidative metabolites of S-2474. In this study, we discovered a novel skeleton, the 2,3-dihydrobenzofuran derivative, which inhibited PGE(2) production at a very low concentration and was effective in the anti-carrageenin footpad edema assay.

Studies on the alkaloids of menispermaceous plants. Part CCXLIX. Total synthesis of optically active natural isotetrandrine, phaeanthine, and tetrandrine

Natural phaeanthine (1a), isotetrandrine (lb), and tetrandrine (1c), belonging to the oxyacanthine–berbamine series of the bisbenzylisoquinoline alkaloids, have been synthesised by a stepwise route. One of the benzyliso-quinoline nuclei was constructed initially, and joined by the Ullmann method through ether linkages to protected phenethylamine and phenylacetic acid units. The phenylacetic acid portion was activated by formation of its nitrophenyl ester and condensed with the phenethylamine unit (protected by a t-butoxycarbonyl group) to form a macrocyclic amide. The latter was converted by Bischler-Napieralski cyclisation and reduction into the desired alkaloids without formation of any structural isomers.

Oxidation of α-Ketoaldehyde by Thiamine and Hydride Acceptor

An adduct of phenylglyoxal with thiamine was readily converted to phenylglyoxylate and thiamine by the action of organic hydride acceptors such as 2, 6-dichlorophenol indophenol, trityl cation, 2-methyl-3-benzylidene-indolenium salt and N-methylnicotinamide. Similar hydride transfer reaction was observed for the adduct of methylglyoxal with thiamine. Direct conversion of phenylglyoxal to phenylglyoxylate by 2, 6-dichlorophenol indophenol was found to occur in the presence of TPP and base. The results indicate a new catalytic role for thiamine in the conversion of α-ketoaldehyde to α-ketoacid.