Hydantoin therapeutic agents

DETAILED DESCRIPTION OF THE INVENTION In accordance with the process employed for obtaining the novel dextrorotatory compounds of this invention, a corresponding racemic or dl-spiro-hydantoin having the same general structural formula as previously indicated for the optically-active compound is contacted with at least an equimolar amount of 1-brucine or a similarly optically-active alkaloid like cinchonidine in a suitable reaction-inert organic solvent preferably selected from the class consisting of lower alkanols.
The resulting diastereoisomeric salts are then separated by means of fractional crystallization and the less soluble salt is converted to the desired optically-active spiro-hydantoin by means of decomposition with acid in a conventional manner.
In accordance with a more detailed consideration of the aforementioned method of resolution of this invention, the first step leading to the production of the diastereoisomers is preferably carried out in a lower alkanol solvent of from one to three carbon atoms using 1-brucine as the resolving agent of choice.
In practice, it is usually preferable to employ equimolar amounts of racemic compound and resolving agent in order to minimize cost and to maximize purity of product, but a slight excess of alkaloid can be used without demonstrably affecting the outcome of the salt-formation step or the nature of the final product obtained.
Needless to say, time is not critical in this connection and is necessarily dependent upon the nature of the starting materials, their concentration in solution and the actual temperatures employed.
Upon completion of the salt-formation step, the desired diastereoisomer normally separates from the mixture by fractional crystallization and this usually requires a period of from about 2 to about 24 hours within a crystallization temperature range of from about -20.
degree.
C.
up to about 60.
degree.
C.
for the present purposes at hand.
The diastereoisomer is then further purified by means of recrystallization, preferably using the same type alkanol solvent earlier employed in the salt-formation step, until full optical purity is achieved, i