Masanobu Yatagai

Structure determination of metabolites isolated from urine and bile after administration of AY4166, a novel d-phenylalanine-derivative hypoglycemic agent

Molecular structures of 10 metabolites, which were isolated from urine (M1-M8) or bile (M9 and M10) after administration of AY4166 (N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine), a novel amino acid derivative with hypoglycemic activity, have been elucidated by mass spectrometry and nuclear magnetic resonance. Four of these (M1, M2, M3 and M8) were determined to be hydroxyl derivatives of AY4166, two (M9 and M10) were carboxylate derivatives via oxidization of M2 and M3, three (M4, M5 and M6) were glucronic acid conjugates and the other (M7) was a dehydro derivative. The estimated structures for M1, M2, M3, M7, M8, M9 and M10 were confirmed by the coincidence of the retention time of HPLC, MS and 1H NMR spectra between the isolated metabolites and authentic synthesized substances. For three glucronic acid conjugates, M4, M5 and M6, structural confirmation was performed by a selective enzymatic digestion with beta-glucronidase. M1 and M2/3 were about 5-6 and 3 times less potent than AY4166, respectively, and M7 was almost as potent as AY4166.

One-Pot Conversion of Serine and α-Methylserine Derivatives to the Corresponding Cysteines and Selenocystines by Using Chalcogenophosphate Reagents

Abstract The one-pot reactions of N-acetylserine methyl ester and N-acetyl-α-methylserine methyl ester with Lawessons or Woollins’ reagent directly produced the corresponding cysteine or selenocysteine derivatives in moderate yields. The transformation would be initiated by phosphorylation of the hydroxy group, rather than chalcogenation of the amide group, and involve the oxazoline as a key intermediate. Supplemental materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. GRAPHICAL ABSTRACT

Efficient 1,4-asymmetric induction utilizing electrostatic interaction between ligand and substrate in the asymmetric hydrogenation of didehydrodipeptides

Electrostatic interaction between the amino group of the achiral 3-dimethylaminopropylidenebismethylenebis(diphenylphosphine)(1) and the carboxy group of the substrate enabled an effective 1,4-asymmetric induction in the RhI-catalysed hydrogenation of didehydrodipeptides, to give (S,S)- or (R,R)-products selectively. The selectivity reached up to 94% diastereoisomeric excess with acetyl didehydrodipeptides and 92% with benzyloxycarbonyl substrates.