Abstract
A practical synthetic route to optically active [2R]- and [2S]-1-alkylamino-3-aryloxy-2-propanols (β-blockers) from [2R]-2, 3-O-isopropylideneglyceraldehyde ([R]-1) was developed. Synthesis of the [S]-isomers was carried out as follows. Borohydride reduction of [R]-1 in the presence of excess alkylamine followed by alkoxycarbonylation, acid hydrolysis, and cyclization under K2CO3 catalysis gave [5S]-3-alkyl-5-hydroxymethyl-1, 3-oxazolidin-2-ones, the tosylates of which were coupled with various phenols then hydrolyzed by alkali treatment to give [S]-(-)-β-blockers (e. g., propranolol, carteolol) in satisfactory yields. [R]-, [S]-, and rac-pindolol were synthesized from the corresponding 3-isopropyl-5-(2-methyl-3-nitrophenoxymethyl)-1, 3-oxazolidin-2-one by application of the Leimgruber-Batcho method.
