Yoshio Toyomaki

The use of 13C-labelling to prove that creatinine is oxidized by mammals into creatol and 5-hydroxy-1-methylhydantoin

Creatinine 1 is not an end-metabolite but a precursor for three heterocycles, 2-amino-5-hydroxy-1-methyl-4(5H)-imidazolone (creatol)2,1-methylimidazolidine-2,4-dione 4 and its 5-hydroxy derivative 5; this is now proven directly by administration of [Me-13C]creatinine 1, to a uraemic rat and subsequent isolation of the corresponding labelled metabolites 2, 4 and 5 from its urine.

Syntheses and properties of optically active 2-substituted taurines

The synthesis of nine 2-substituted taurines (5a–i), including the marine natural product D-cysteinolic acid (5f), are described. These involve the successive conversion of N-t-butoxycarbonyl(Boc)-protected amino acid esters (1) into the N-Boc-2-aminoethanols (2), their O-mesylated derivatives (3), the deprotected 2-aminoethyl methanesulphonates (4), followed by the replacement of the mesyloxy group by a sulpho group to give the optically active taurines (5a–e,g–i). Hydrogenolysis of 2-benzyloxymethyltaurine (5e) gives D-cysteinolic acid (5f). The structure of another of the products, (5b), is also confirmed by an alternative synthesis from N-Boc-valine methyl ester (1b)via two β-bromoethylamine derivatives, (6b) and (7b).

Simple method for determination of A1c-type glycated hemoglobin(s) in rats using high performance liquid chromatography.

We have developed a new chromatographic method for the determination of rat glycated hemoglobins by cation exchange high-performance liquid chromatography. The hemoglobins were eluted by a two-step gradient, and the total assay time, including re-equilibration of the column, was 27 min. Two A1c type and one pre-A1c type rat glycated hemoglobins were separated and measured. The change in major HbA1c of rats, in which diabetes was induced by streptozotocin and which were subsequently treated with insulin, was monitored. In diabetic rats (n = 10, average blood glucose greater than 300 mg/dL), major HbA1c rose to 3.39 +/- 0.06% compared with controls (n = 10, 1.20 +/- 0.03%) during 5 wk. Insulin treatment decreased the HbA1c from 3.48 +/- 0.16% to 2.74 +/- 0.15% (p less than 0.01) in 6 wk. This method was also effective for the determination of mouse HbA1c.

The chemical conversion of C-terminal glycines in peptides into taurine

The first chemical conversion of C-glycine in dipeptides into taurine has been achieved using a general substitution of a sulpho group for a halogeno or mesyl group via the corresponding amino acid 2-halogenoethyl-or 2-methanesulphonyloxyethyl-amides, each of which was prepared from the ethanolamide obtained by LiBH4 reduction of a protected dipeptide containing a C-glycine ester.