Yoshinobu Yanagawa

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.