Active amines resolve stereoisomers
Liquid membranes clean waste water
Commercial production of a growing number of biologically active com pounds hinges on the separation of optically active isomers. For example, L-dopa (L-3,4-dihydroxyphenylalanine), a drug used against Parkinson's dis ease, must be separated from a racemic mixture of D, L-dopa, since the D-isomer is not therapeutic and causes unwanted side effects. Mount ing interest in separation of stereoiso mers has prompted Hoffmann-La Roche, Inc., to offer a laboratory test kit with samples of six resolving agents. The Nutley, N.J., firm will make commercial quantities of the agents and expand its line later. The kit, which will sell for about $20, contains six ampules—each with 5 millimoles of an optically active amine. The amines are ( + ) - and (—)α-methylbenzylamine and the corres ponding iV-methyl and Af,N-dimethyl derivatives, as their free bases. A number of other firms offer opti cally active isomers for resolution. Japan's Ajinomoto, for example, has specialized in optically active amino acids. Norse Laboratories, Inc., Santa Barbara, Calif., has expanded its line of resolving agents from six in 1967 (C&EN, May 1,1967, page 14) to 600. Tedious. Separation of optically ac tive isomers is a tedious procedure that has been described as more black magic than science. The most com mon method involves conversion of a racemate to a mixture of diastereomers via salt formation. Common re solving agents for this purpose include alkaloids and semisynthetics such as dehydroabietylamine and D-camphorsulfonic acid. The salts are separated and purified by crystallization or chro matography and then regenerated to the original isomers. Enzymic and chromatographic methods have been developed for the direct separation of optically active isomers. Roche developed the manufacturing know-how to produce the six optically active amines in commercial quanti ties in its work on a commercial proc ess for the production of L-dopa. Roche finds that 2,3,4,6-diacetone-2keto-L-gulonic acid (an intermediate in the firm's ascorbic acid synthesis) will separate ( + ) -a-methylbenzylamine from its racemate, and tartaric acid will separate the (—)-isomer (Belgian patent 745,032). Although chemically identical, ste reoisomers differ markedly in such biological properties as taste, odor, and toxicity, and in pharmacology. In some cases, it is almost as if two dif-
Use of permeable liquid membranes for separation processes has moved successfully into a new area—waste water effluent treatment. According to Dr. Norman N. Li, of Esso Research and Engineering Co.'s laboratories in Linden, N.J., the membranes can be used to selectively remove contami nants from refinery effluents. The original membrane use was for hydro carbon separation in refinery process ing (C&EN, Oct. 5, 1970, page 36). Development of separation by liquid membranes resulted from the obser vation that saponin, a natural surfac tant, forms very strong films at oil/ water interfaces. The films are so strong that in a Du Nuoy ring experi ment the ring can actually lift and sus pend the film in the upper oil phase. By forming droplets surrounded by membranes and passing them through a solvent, contaminants in the drop lets are selectively removed. The problems of maintaining the mechanical integrity of the encapsu lated droplets have been overcome through improved emulsion tech niques, which produce droplets with diameters as low as ΙΟ-3 cm. The per meability of the membranes may also be controlled to some extent through chemical modification in situ. Emulsion. In adapting the separa tion technique to waste water treat ment, Dr. Li tells C&EN that the mem brane material is used to produce an emulsion of solvent droplets. The droplets are mixed in· a tower of waste water, where contaminants selectively permeate the film. The droplets con taining the contaminants are trans ferred to a regeneration unit, where the emulsion phase is de-emulsified and conditioned for re-use. The con taminants are then confined and the waste water is released. Actual waste treatment is accom plished through the intense mixing of the membrane encapsulated droplets with the waste water. Dr. Li notes that it is remarkable that the liquid membranes have sufficient strength to withstand the violent mixing. He believes that the strength is achieved by developing the very small droplets in the emulsification stage. The small droplets tend to agglom erate, and so intense mixing also of fers the advantage of countering this tendency. On the other hand, liquid membranes are more easily ruptured in the regeneration stage. This is an advantage not offered, at least to the extent of liquid membranes, by more conventional polymeric materials.
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C&EN JUNE 7, 1971
Chemist uses kit of resolving agents
ferent and structurally unrelated com pounds were involved. As a result of these biological differences, an increas ing number of drugs are being sep arated from their optical isomers. For example, L-dopa is now administered in large doses, of 2 to 5 grams per day. When only D, L-dopa was available, even larger doses were re quired for efficacy. However, patients generally could not tolerate higher doses because of the toxic properties of the D-isomer, and so the drug could not be used with them. In a number of other commercial processes, clean separation of optical isomers is also crucial, according to Hoffmann-La Roche. In the field of morphinans, for instance, levorphan is a powerful narcotic similar to mor phine, whereas its methylated stereo isomer, dextromethmorphan, is a nonaddicting antitussive (cough-pre venter). High optical purity of dex tromethmorphan is mandatory be cause any significant amount of L-isomer could give rise to the addictive levorphan through enzymic demethylation, a common metabolic pathway. Vitamins. Vitamins produced syn thetically, such as biotin and panto thenic acid, require a resolution step since only naturally occurring isomers possess biological activity. Except for glycine, all 20 common oj-amino acids contain at least one asymmetric car bon atom, and all have the same ab solute L-configuration. In other commercial processes for separation of stereoisomers, both a racemate and one of its optical iso mers may be produced and used in therapy. For example, chlorphenira mine, a racemic compound, and its Disomer are used as antihistamines. Racemic amphetamine and its D-iso mer are used as stimulants.
