ABSOLUTE-CONFIGURATION OF GLYCEROL DERIVATIVES .5. OXPRENOLOL ENANTIOMERS

Synthesis of the optical isomers of oxprenolol [(2R)- and (2S)-1-(isopropylamino)-3-(o-allyloxyphenoxy)-2-propanol ((2R)- and (2S)-1)] was accomplished starting from (2R)- and (2S)-1-tosyloxypropane-2, 3-diol acetonide. Cupra A CD spectra are reported for the intermediate diols [(2R)- and (2S)-1-(o-allyloxyphenoxy)-2, 3-propanediol ((2R)- and (2S)-3)] and the oxprenolol isomers. These spectra were consistent with the previous results, allowing assignment of the absolute configuration based on transitions in the 285 nm region. The NMR spectra of the oxprenolol enantiomers (2R)- and (2S)-1 in the presence of a chiral shift reagent, Eu(hfbc)3, and of the amides formed from optically active α-methoxy-α-trifluoromethylphenacetyl chloride (Mosher reagent) were examined. The spectra of the diastereoisomeric amides showed upfield shifts of partial resonances for the isopropyl methyl groups, which result from shielding effects of the aromatic ring of the acyl fragment. The assignments were confirmed by use of specifically deuterated oxprenolol amides. © 1978, American Chemical Society. All rights reserved.