Kinetic Resolution of Aryl Glycidyl Ethers: A Practical Synthesis of Optically Pure b-Blocker—S-Metoprolol

Abstract

Kinctic re>olution of ( = ) -q l glycidyl ethers using (R,R)-sden Co(lll)OAc and water orovlded enanriorn~'r~callv oure arvlelvcidvl ether and > -< 1-&lglycerol derivatices with high enanti~me&~excess.lickion ion of this approach to (9-metoprolol has been described.Chirality, in the context of biological activity, is an important phenomenon because great differences in activities are observed for enantiomers of a hioactive substance.For example, (9-isomer of all aryloxypropanolamine type p-blockers ( 1) is clinically useful, while the corresponding (R)-isomer has undesirable properties.1 Chiral glycidyl derivatives are perhaps one of the most versatile C3-chiral synthons with numerous applications for p-blockers, M A 0 inhibitors, alkyl glycerophospholipids and other pharmaceuticals as well