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Metaraminol2 is a potent catecholamine deplete!' in heart tissue in a number of animal species.3"6 Shore, Busfield, and Alpers7 reported that ( -)metaraminol is rapidly taken up and retained by sympathetic nerve endings, generally with a stoichiometric exchange between metaraminol and norepinephrine. Grout8 demonstrated a significant fall in blood pressure with ( -)-metaraminol in four of six hypertensive patients. Besides an indirect action of norepinephrine release from tissue storage sites, ( -)-metaraminol has been shown to have direct, sympathomimetic action on the effector organ.9 A large variation in the relative direct and indirect vasopressor activity is seen among the four possible stereoisomers of ephedrine in the anesthetized dog with the (1X2/?) and (15,25) isomers exhibiting less direct activity than the (l/?,25) form.10 Thus, it was of interest to prepare the four optical isomers of metaraminol to determine whether any of these retained the potent indirect release-depletion action seen with ( -(-metaraminol (IR.2S) together with a. reduction of the direct sympathomimetic property.Since quantities of both ( -(-metaraminol and the mother liquors from its resolution11 were available to us. we chose to epimerize the benzylic hydroxyl rather than to synthesize and resolve the t It reo isomer. The route chosen (i.e., introduction of a benzylic group prior to hydrolysis, while longer than direct hydrolysis of the oxazoline, permitted the final product to be readily isolated and purified (Scheme I).Our results agree with those of Dirkx12 who assigned the (IR,2S) configuration to (-(-metaraminol on the basis of optical rotory dispersion and lend further support to the utility of coupling constants of the benzylic hydrogen to demonstrate the enjthro or ihreo configuraf 1 1 Deceased May 1908.(2.) a-( l-AminoethyO-m-hydroxvbenzyl alcohol. The ( -}-erythro isomer a< the í -b)-bitartrate is Pressonex® or Aramine*.

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Ausgehend von (‐)‐Metaraminol (I) und den Mutterlaugen der Gewinnung von optisch aktivem (I) wurden durch Benzoylierung zu (II), anschließende Umsetzung mit Thionylchloridzum Oxazolin (III) und saure Hydrolyse zu (IV) die verschiedenen vier isomeren Metaraminole dargestellt und auf ihre antihygertensive Wirksamkeit untersucht.