GB785013A - Acylated dl-proline salts and their use in obtaining d-and l-prolines separately - Google Patents

Abstract

The invention comprises the salt of N-3,5-dinitrobenzyl - L - proline with D - (-) - threo-1 - p - nitrophenyl - 2 - amino propane - 1,3-diol and the salt of N-3,5-dinitrobenzoyl-D-proline with L - (+) - threo - 1 - p - nitrophenyl-2 - amino propane - 1,3 - diol and the use of these salts and the corresponding enantiomorphs (enantiomorphic salts) in obtaining separately D- and L-proline. The salts are obtained by reacting L-(+)- or D-(-)-threo-1-p-nitro phenyl-2-amino propane-1,3-diol as resolution agent with N-3,5-dinitro benzoyl-DL-proline in an inert solvent in which only one of the two enantiomorphs gives a salt with the resolution agent, which is sparingly soluble in the solvent and separating the salts of the two enantiomorphs by means of the difference in their solubilities; the separated salts may be decomposed by treatment with a base followed by acidification to yield the dinitrobenzoyl D-and L-prolines which are saponified separately to D- and L-prolines. The inert solvent may be water or preferably an aliphatic alcohol, e.g. ethanol. The D-form of the resolution agent forms a sparingly soluble salt with only the N-3,5 - dinitro benzoyl - L - proline and the L-form of the resolution agents gives a sparingly soluble salt with the N-3,5-dinitrobenzoyl-D-proline, the other enantiomorphic salts formed being retained in solution. The method may be used in the resolution of DL-proline, the N-3,5-dinitrobenzoyl DL-proline being obtained by direct acylation of DL-proline or by reacting 3,5-dinitrobenzoyl chloride with an ester or like functional derivative of DL-proline and then regenerating the N-acylated amino acid. The resolution salt of the acylated L-proline may be converted to the free dinitrobenzoyl-L-proline or to L-proline, racemised and then returned to the resolution system. In this manner, naturally occurring L-proline may be substantially completely converted to D-proline; the reverse procedure may also be followed with naturally occurring D-proline. In examples: (1) N - 3,5 - dinitrobenzoyl - DL - proline is dissolved in water and the resolution agent in L-form is added; after stirring at 40 DEG C., the precipitated salt is filtered off and decomposed by aqueous caustic soda, the liberated resolution agent is removed, the aqueous residue is acidified and the resulting acylated D-proline is recovered, hydrolysed with aqueous HCl and D-proline is obtained from the hydrolysate; the filtrate remaining after removal of the resolved salt of the acylated D-proline contains the salt of the L-resolution agent with the acylated L-proline and is treated as above to recover crude acylated L-proline which is then hydrolysed to L-proline; (2) the crude acylated L-proline obtained as in (1) is treated in water with the D-form of the resolution agent whereby the salt of the D-resolution agent with acylated L-proline is recovered and treated as above to give a purer L-proline. Specification 745,097 is referred to.