Yoshio Ohara

A novel synthetic method of HMG-CoA reductase inhibitor NK-104 via a hydroboration-cross coupling sequence

Abstract The regioselective hydroboration of ethyl ( 3R, 5S )-3,5-isopropylidenedioxy-6-heptynoate, followed by the cross-coupling reaction with an aryl halide, provides ethyl ( 3R, 5S, 6E )-7-aryl-3,5-isopropylidenedioxy-6-heptenoate, a precursor of a highly potent HMG-CoA reductase inhibitor NK-104.

First systematic chiral syntheses of two pairs of enantiomers with 3,5-dihydroxyheptenoic acid chain, associated with a potent synthetic statin NK-104

First systematic chiral syntheses of two pairs of enantiomers with 3,5-dihydroxyheptenoic acid chain, associated with a potent synthetic statin NK-104 are reported. A pair of syn diol isomers (NK-104 and its enantiomer) was obtained efficiently by diastereomeric resolution. The synthesis of a pair of anti diol isomers (3-epimer and 5-epimer) was accomplished effectively by the asymmetric aldol reaction followed by anti stereoselective reduction as key steps. Their purity determinations were effected by chiral HPLC analysis.

Synthesis of corey lactone via highly stereoselective asymmetric Diels-Alder reaction

Abstract We have succeeded in a highly stereoselective asymmetric Diels-Alder reaction between a chiral acrylate 3a derived from commercially available D-pantolactone 2 and 5-benzyloxymethyl-cyclopentadiene 4 to give the adduct 5a in 94% d.e. and 79% yield for the synthesis of Corey lactone 1 .

A new synthetic route of corey lactone having ω-side chain

Corey lactone having ω-side chain 1a is an important intermediate for syntheses of prostaglandins. Now we have succeeded in developing a new synthetic route of 1a from methylenecyclopentanone having ω-side chain 2a. The new synthetic route has two crucial steps as follows. 1) Hydroxymethyl unit introduction by using organozinc reagent. 2) Oxidation of diol to lactone by using N-oxoammonium salt in combination with sodium bromite.