Tadaaki Ohgiya

Synthetic studies on new sugar oxetanose: Synthesis of D-erythrooxetanose and its reaction with silylated adenine derivative

Abstract Related to antiviral antibiotic oxetanocin, l.O-acetyl-β-D-erythrooxetanose was synthesized in two different methods, and coupling reaction with silylated adenine provided α- and β-L-threofuranozyl adenines via an unusual neighboring group participation.

Optimization of a novel series of potent and orally bioavailable GPR119 agonists

We describe the discovery and optimization of a novel series of furo[3,2-d]pyrimidines as G protein-coupled receptor 119 agonists. Agonistic activity of 4 (EC50=129nM) was improved by replacing the intramolecular hydrogen bond between the fluorine atom and the aniline hydrogen in the head moiety with a covalent C-C bond to enhance conformational restriction, which consequently gave a lead compound 12 (EC50=53nM). Optimized compound 26, which was identified by the further optimization of 12, exhibited potent activity (EC50=42nM) with improved clearance in liver microsomes and induced a 33% reduction in blood glucose area under the curve at a dose of 10mg/kg in an oral glucose tolerance test in C57BL/6N mice.

Oxetanocin—Oxetanose Chemistry: Lewis Acid Promoted Glycosidations of the D-Erythrooxetanose Derivatives

Abstract Upon treatment of 1-O-acetyl-D-erythrooxetanoses (17a,b and 26) with trimethylsilyl N-benzoyladenine or allyltrimethylsilane in the presence of SnCl4, the ring expanded products (18, 19 and 29) or the acyclic compounds (27 and 28) were obtained. The reaction mechanism involving a novel ring opening process is discussed.

A novel method for the synthesis of anomerically allylated C-glycofuranosides. An unusual Lewis acid-catalysed rearrangement of an oxetanosyl-N-glycoside to furanosyl-C-glycosides

An oxetanosyl-N-glycoside is converted into furanosyl-C-allylglycosides with allyltrimethylsilane in the presence of Lewis acid.