Toru Yamano

Enantioselective hydrogenation of β-keto esters catalyzed by P-chiral bis(dialkylphosphino)ethanes-Ru(II)

Abstract Asymmetric hydrogenation of keto esters using a BisP ∗ RuBr 2 catalyst is reported. High enantioselectivities up to 98% were achieved in the hydrogenation of β-keto esters.

Practical synthesis of (R)-(+)-6-(1,4-dimethoxy-3-methyl-2-naphthyl)-6-(4-hydroxyphenyl)hexanoic acid: a key intermediate for a therapeutic drug for neurodegenerative diseases

Abstract A practical method for the preparation of ( R )-(+)-6-(1,4-dimethoxy-3-methyl-2-naphthyl)-6-(4-hydroxyphenyl)hexanoic acid ( R )- 2 , a key intermediate for a therapeutic drug for neurodegenerative diseases, has been developed. rac -Methyl 6-(1,4-dimethoxy-3-methyl-2-naphthyl)-6-(4-(propionyloxy)phenyl) hexanoate rac - 9b was synthesized from 2-methylnaphthoquinone in seven steps. An optically active ester ( R )- 9b was readily obtained from the corresponding racemic ester by lipase-catalyzed resolution, followed by sulfation or phosphorylation. Sulfation by a sulfur trioxide pyridine complex or phosphorylation by phosphoryl chloride enabled facile isolation of the optically active ester simply by extraction. Optically active acid ( R )- 2 was synthesized in excellent enantiomeric excess by hydrolysis of ( R )- 9b followed by recrystallization. The present synthesis of ( R )- 2 was accomplished in 10 steps without requiring chromatographic purification.

Design, synthesis, and structure-activity relationships of spirolactones bearing 2-ureidobenzothiophene as acetyl-CoA carboxylases inhibitors.

The co-crystal structure of the human acetyl-coenzyme A 2 (ACC2) carboxyl transferase domain and the reported compound CP-640186 (1b) suggested that two carbonyl groups are essential for potent ACC2 inhibition. By focusing on enhancing the interactions between the two carbonyl groups and the amino acid residues Gly(2162) and Glu(2230), we used ligand- and structure-based drug design to discover spirolactones bearing a 2-ureidobenzothiophene moiety.

Synthesis of a key intermediate for D-biotin via 1,3-cycloaddition of a thiocarbonyl ylide and sila-Pummerer rearrangement

An efficient preparation of a d-biotin intermediate, (±)-(3aα,4α,6aα)-1,3-dibenzyl-3a,4,6,6a-tetrahydro-4-hydroxy-1H-thieno[3,4-d]imidazol-2(3H)-one was accomplished by use of 1,3-cycloaddition of a thiocarbonyl ylide, Curtius rearrangement and sila-Pummerer rearrangement. Addition of p-toluenesulfonic acid was found to be effective to promote sila-Pummerer rearrangement of sterically unfavorable anti-2-trimethylsilyl sulfoxide