Kimio Hamamura

α-tocopherol affects the urinary and biliary excretion of 2,7,8-trimethyl-2(2′-carboxyethyl)-6-hydroxychroman, γ-tocopherol metabolite, in rats

In this study, we investigated a change in the excretory content of 2,7,8-trimethyl-2(2′-carboxyethyl)-6-hydroxychroman (γ-CEHC), a γ-tocopherol (γ-Toc) metabolite, in rat urine and bile by using a new high-performance liquid chromatography-elelectrochemical detection (HPLC-ECD) method. In this determination, CEHC [α- and γ-CEHC, where α-CEHC-2,5,7,8-tetramethyl-2(2′-carboxyethyl)-6-hydroxychioman] in the biological specimens were treated with 3 N methanolic HCl to hydrolyze conjugates and to promote esterification. The methylated samples were extracted by n-hexane/water (1∶2). The analyses of the methyl esters of α-CEHC and γ-CEHC were performed by an HPLC-ECD using an ODS-3 column at 35°C. The mobile phase was acetonitrile/water (45∶55, vol/vol) containing 50 mM sodium perchlorate. After rat urine and bile samples, respectively, were methylated as described above, methylated biliary metabolites were identified by liquid chromatography mass spectrometry as methyl esters of γ-CEHC. Furthermore, we examined the differences in the excretion of γ-CEHC between rat urine and bile after an oral administration of γ-Toc or α- +γ-Toc by the above HPLC method. In the γ-Toc group, each vitamin E-deficient rat was given 0.5 mL of a stripped corn oil preparation containing 10 mg of γ-Toc. In the α- +γ-Toc group, the rat was given 10 mg of α-Toc and 10 mg of γ-Toc. The content of γ-CEHC in rat urine from the α- +γ-Toc group was increased more in comparison to the γ-Toc group at 18–36 h after oral administration. Moreover, the content of γ-CEHC in rat bile in the α- +γ-Toc group was increased more in comparison to the γ-Toc group at 6–18 h after oral administration. Therefore, we have suggested that γ-CEHC was shifted mainly to urinary excretion after γ-CEHC had been excreted into the bile. Furthermore, we assume that α-Toc may affect the metabolism of γ-Toc to γ-CEHC in the body.

Large scale synthesis of N-benzyl-4-formylpiperidine through partial reduction of esters using aluminum hydride reagents modified with pyrrolidine

Abstract The modification of sodium bis(2-methoxyethoxy)aluminum hydride (SMEAH) with pyrrolidine provided a highly selective reducing agent to transform N -benzyl-4-ethoxycarbonylpiperidine into N -benzyl-4-formylpiperidine 1 under mild conditions. However, this simple modification led to a significant amount of N -benzyl-4-(pyrrolidin-1-ylmethyl)piperidine 4 due to overreduction of an intermediate. Our extensive research revealed that an alkaline base such as potassium tert -butoxide could suppress the formation of the by-product to give the desired aldehyde, enabling us to establish a viable synthetic process for a key intermediate of donepezil hydrochloride. The potential applications of this reagent are also described.

Synthesis of 2S,4′R,8′R‐α‐[5‐methyl‐14C]tocopheryl acetate

2-Ambo-γ-tocopheryl acetate 4 was synthesized starting from 2,3-dimethylhydroquinone monobenzoate 1 and natural phytol 2. 2S,4′R,8′R-enantiomer 6 was separated using preparative Chiralpack OP (+) column HPLC. Copyright