Masaki Naito

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.

Radical deoxygenation and dehalogenation of nucleoside derivatives with hypophosphorous acid and dialkyl phosphites

Hypophosphorous acid and dialkyl phosphites are effective radical reducing agents for O-thiocarbonyl groups or halides at the sugar part of nucleoside derivatives and give the corresponding hydrocarbons in high yield.

Practical synthesis of 9-(2,3-dideoxy-2-fluoro-β-d-threo-pentofuranosyl)adenine (FddA) via a purine 3′-deoxynucleoside

Abstract A practical synthesis of 9-(2,3-dideoxy-2-fluoro-β- d - threo -pentofuranosyl)adenine ( 1 , FddA) via a 6-chloro-9-(3-deoxy-β- d - erythro -pentofuranosyl)-9 H -purine ( 6 ) is described. Fluorination at the C2′-β position of the purine 3′-deoxynucleoside was improved by the introduction of 6-chloro group, and proceeded in moderate yield. The total yield of FddA from readily available starting material 6 was 35%.

A Facile Synthetic Method for 3′-α-Fluoro- 2′,3′-dideoxyadenosine

Abstract A facile method for the synthesis of 3′-α-fluoro-2′,3′-dideoxyadenosine (5) has been developed using a novel rearrangement of 3′-β-bromine to the 2′-β position during 3′-α fluorination.