2'-Substituted alkaloids of the cinchona series, especially 2'-substituted quinine, quinidine, cinchonine, cinchonidine and their dihydro analogs, and their salts, are prepared by treating ar-N-oxides of the alkaloids with the corresponding organometallic reagent and, if desired, converting the free bases thus formed into pharmaceutically acceptable acid addition salts. The new compounds are pharmacologically active, especially anti-malarially and anti-arrhythmically.
This application is a divisional of application Ser. No. 27,119, entitled "2'-Substituted-Cinchona Alkaloids," filed Apr. 9, 1970 now U.S. Pat. No. 3,643,552, which in turn is a continuation-in-part of application Ser. No. 692,277, entitled "2'-Substituted-Cinchona Alkaloids," filed Dec. 21, 1967 now abandoned.
Optically active .alpha.-hydroxyethers are prepared from prochiral .alpha.-ketoethers by heterogeneous hydrogenation using platinum catalysts in the presence of a chiral nitrogen base in high chemical and optical yields, since this type of hydrogenation selectively hydrogenates only one diastereomer virtually to completion. The yields may be substantially increased by adding a solid, strong base which has a racemizing effect on the non-hydrogenatable diasteromer.
