Junki Katsube

Studies on the activity of l-THREO-3,4-dihydroxyphenylserine (l-DOPS) as a catecholamine precursor in the brain comparison with that of l-DOPA

L-Threo-3,4-dihydroxyphenylserine (L-DOPS) was compared with L-3,4-dihydroxyphenylalanine (L-DOPA) with respect to their activities as central amine precursors. The apparent Km value (the substrate affinity) of L-DOPS for aromatic L-amino acid decarboxylase was nearly equal to that of L-DOPA, whereas the vmax value (the rate of decarboxylation) of L-DOPS was much smaller than that of L-DOPA, the penetration of L-DOPS into the brain through the blood-brain barrier was found to be smaller (about one-fourth) than that of L-DOPA but, for an amine precursor, it was still substantial. Unlike L-DOPA, L-DOPS did not cause a marked accumulation of norepinephrine (NE), the corresponding catecholamine in the brain, but nialamide, a monoamine oxidase inhibitor significantly enhanced the L-DOPS-induced rise of NE. Moreover, the brain concentration of 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG), the principal end metabolite of NE, was increased markedly by L-DOPS. These results suggest that L-DOPS may act as an NE precursor in the brain and activate NE neurons by increasing the turnover rate of NE.

Studies on the central action of L-threo-3,4-dihydroxyphenyl-serine (L-threo-DOPS) in FLA-63-treated mice

In order to clarify the central action of L-threo-DOPS, the effect of benserazide on behavioral and biochemical changes by L-threo-DOPS in FLA-63-treated mice was studied. L-threo-DOPS in combination with nialamide markedly increased both the locomotor activity and the concentrations of the brain, heart and kidney norepinephrine (NE) in the FLA-63-treated mice. Benserazide at low doses did not alter either the rise of the brain NE level or the increase in locomotor activity, whereas it significantly inhibited the rise of the heart and kidney NE levels. Benserazide at a high dose significantly inhibited all of them. These results suggested that the increase in locomotor activity might be mediated via activation of the central noradrenergic neurons system by L-threo-DOPS.

Stereocontrolled approaches to 9(0)-methanoprostacyclin☆

Abstract A stable PGI2 analog (methanoprostacyclin 2 ) was synthesized starting from 5-norbornene-2,3-dicarboxylic anhydride.

Synthetic Studies on Cyclopentane Derivatives:Part II. Reactions of Enol Ethers of Cyclopentane-1, 3-dione Derivatives with Cyanide Ion

Reactions of enol ethers of cyclopentane-1,3-dione derivatives (I) with cyanide ion were investigated in order to develope new synthetic routes to 3-functionalized-2-cyclopenten-1-one derivatives from I.I could be converted to the 3-cyano-2-cyclopenten-1-one skeleton by several procedures for hydrocyanation, among which Nagata’s reagents (HCN-triethylaluminium, diethylaluminium cyanide) were proved to be potent ones.Reactions of enol ethers of 4-hydroxy-cyclopentane-1,3-dione derivatives were also investigated. From 4-hydroxy-3-methoxy-2-cyclopenten-1-one derivatives (V) 1,4-addition type products with the 4-hydroxy-3-cyano-2-cyclopenten-1-one skeleton (VIII) were obtained as sole isolatable products. NMR studies of some hydroxy-cyclopentenone derivatives were also described.