Takeaki Naito

Determination of β-carbolines in foodstuffs by high-performance liquid chromatography and high-performance liquid chromatography-mass spectrometry

Abstract A high-performance liquid chromatographic method combined with fluorimetric detection is described for the determination of β-carboline(norharman) and 1-methyl-β-carboline (harman). The analysis of foodstuffs for the identification of β-carbolines is facilitated by clean-up of samples using Bond Elut PRS cartridges. Recoveries were excellent. Further, a high-performance liquid chromatographic-mass spectrometric method was also developed for their identification. The concentration of β-carboline among the foodstuffs and alcoholic beverages varied greatly. Also, norharman and harman were observed in uncooked foodstuffs, whereas acetaldehyde was found in most fermented food. The toxicological implication of β-carbolines in foodstuffs is discussed.

Radical cyclizations of oxime ethers connected with aldehydes or ketones : A new entry to cyclic amino alcohols

Abstract Oxime ethers connected by a tether to aldehydes or ketones efficiently cyclize in a free radical cyclization which is mediated by tributyltin hydride and provide a new entry to the cyclic amino alcohols.

Asymmetric synthesis of (+)- and (-)-coniines and (-)-sedamine by diastereoselective alkylation reaction of ethoxypiperidinone

Diastereoselective alkylation reaction of the chiral 6-ethoxypiperidinones (4) and (5) has been developed and successfully applied to the asymmetric synthesis of piperidine alkaloids, (+)- and (-)-coniines (11) and (12), (-)-sedamine (21), and (-)-allosedamine (22)

Pseudodistomin B: Revised structure and first total synthesis

Abstract The structure of pseudodistomin B, novel antineoplastic piperidine alkaloid, has been revised to 1a on the bases of the degradation reaction and the first total synthesis of (±)-pseudodistomin B acetate ( 1b )

Asymmetric induction at two contiguous stereogenic centers by diastereoface differentiating nucleophilic addition reaction

Abstract Distereoface differentiating nucleophilic of thiophenol to olefins delivers a new concomitant asymmetric construction of two contiguous stereogenic centers and has been successfully applied to the asymmetric synthesis of (+)-diltiazem.

Effect of acetaldehyde on urinary salsolinol in healthy man after ethanol intake

The effect of acetaldehyde on urinary salsolinol (6, 7-dihydroxy-l-methyl-1,2,3,4-tetrahydroisoquinoline) after ethanol intake was investigated. Healthy Japanese male volunteers were divided into two groups, i.e., a normal aldehyde dehydrogenase (ALDH) group of 13 subjects with a low Km isozyme of ALDH and a deficient group of 12 subjects. The subjects were given 0.4 or 0.8 g/kg of ethanol. Blood ethanol and acetaldehyde levels, urinary excretions of salsolinol, norepinephrine, epinephrine and dopamine were determined. A significant elevation of salsolinol in urine was found after intake of 0.8 g/kg of ethanol in the two groups, but the increase in the deficient group was greater than that in the normal group, while 0.4 g/kg of ethanol did not affect the excretion of salsolinol in either group. Blood acetaldehyde was highly correlated with urinary salsolinol (r = 0.88, p less than 0.001) and the correlation coefficient was greater than that between blood ethanol and salsolinol.

Individual difference in urinary excretion of salsolinol in alcoholic patients

Urinary excretion of salsolinol (6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline) in 30 male alcoholic patients during the withdrawal period was determined. They were divided into two groups, i.e., Group A with 14 subjects had a high level of urinary salsolinol (51.9 +/- 40.8 ng/mg creatinine) on admission to a hospital, and Group B with 16 subjects showed a low level of the substance (3.9 +/- 1.9 ng/mg creatinine). Following a sustained drinking bout, urinary salsolinol in Group A declined to a normal level within a few days. We found that the subjects in Group A showed a greater excretion of urinary dopamine and norepinephrine than those in Group B. There were no differences between the two groups in levels of blood ethanol, serum GOT, GPT and gamma-GTP.

First total synthesis of pseudodistomin tetrahydroacetate

Abstract The first synthesis of tetrahydroacetate of pseudodistomin, a novel antineoplastic piperidine alkaloid, was achieved via the route involving the reductive photcyclization of enamide and α-acylamino radical allylation.

Identification of four metabolites of 3-(phenylamino)alanine,a constituent in L-tryptophan products implicated in eosinophilia-myalgia syndrome, in rats

Abstract3-(Phenylamino)alanine (PAA), a contaminant found in l-tryptophan tablets, has been discussed as a possible cause of eosinophilia-myalgia syndrome (EMS). We administered PAA (100 mg/kg) by gastric gavage to Wistar rats to determine its distribution and metabolism. We developed a purification procedure, using Bond Elut SCX cartridges followed by high performance liquid chromatography (HPLC) in order to determine levels of PAA. The level of PAA in blood was 4.22 μg/ml at 5 h and urinary excretion was 21.7 μg for 5 h and 84.6 μg between 5 and 24 h. The amount of PAA in the contents of the large intestine at 5 h was 0.76 μg, indicating poor transfer of PAA to the large intestine. However, the highest concentration of PAA was 12.3 μg/g in the brain, indicating the passage of PAA through the blood-brain barrier. In addition to detecting PAA in the blood and organs, we also detected four metabolites of PAA in urine. We used gas chromatography mass spectrometry to identify PAA in rat liver, as well as N-(hydroxyphenyl)glycine, N-phenylglycine, 3-(pheylamino)lactic acid, and 3-(hydroxyphenylamino)-lactic acid in rat urine. These results suggest that the degradation pathway of PAA is similar to that of phenylalanine.

Metabolism and distribution in the rat of peak E substance, a constituent in L-tryptophan product implicated in eosinophilia-myalgia syndrome

Peak E substance, 1,1′-ethylidenebis[tryptophan], a contaminant found inl-tryptophan tablets, has been suggested as a causative agent for eosinophilia-myalgia syndrome (EMS). Peak E substance (50 mg/kg) was administered perorally to Wistar rats to determine its metabolism and distribution. A purification procedure using Bond Elut C8 cartridges followed by HPLC was developed for the determination of peak E substance. The plasma concentration of peak E substance was 136 ng/ml at 1 h, and urinary excretion was 717 ng at 5 h and 10342 ng for 5–24 h, showing slow excretion of peak E substance into urine. The amount of peak E substance in the contents of the large intestine at 5 h, however, was 3136 Μg, much greater than urinary excretion for 24 h, indicating considerable transfer of peak E substance to large intestine without decomposition by gastric fluid in the stomach. We have detected for the first time not only the occurrence of peak E substance in plasma and urine, but also 1-methyl-tetrahydro-Β-carboline-3-carboxylic acid (MTCA) in blood and organs of rats treated with peak E substance, thereby suggesting MTCA as one of the the metabolites of peak E substance. The amount of MTCA in the contents of the large intestine as well as in urine of rats treated with peak E substance was significantly greater than inl-tryptophantreated rats (50 mg/kg p.o.), demonstrating that MTCA was more readily produced from peak E substance than froml-tryptophan. Finally, we propose acetaldehydeinduced production of MTCA from peak E substance.