Ephedrine, concepts

Starting from the Pt-cinchona modified system, more recently an interesting concept has been developed by Feast and coworkers [144], A chiral acidic zeolite was created by loading one molecule of iM,3-dithianc-l-oxide per supercage of zeolite Y, either during or after the zeolite synthesis. Other chiral zeolites were formed by adsorbing ephedrine as a modifier on zeolites X and Y for the Norrish-Yang reaction [145],... 

Enantioselective separation of ephedrine-t5qje alakaloids in herbal materials Cyclodex-P (30 x 0.250 x 0.250) x BP-20 (1x0.100x0.100) Cryogenic (Chromatography Concepts) [40]... 

This phase saw continuous advances in chemistry and medicine. Organic chemistry was now capable of the synthesis of relatively complex targets by multistep sequences. The concept of systematically preparing a compound series and testing it for a biological effect became common, as exemplified in Ehrlich s quest for antisyphilitic agents. More and more pure natural products were identified and their structures elucidated. Synthetic mimics became a reahty. For example, amphetamines were inspired by the natnral prodnct lead, ephedrine. 

With the first three chiral auxiliaries, 8a-c, low to medium e.e.s of 7 were obtained, far from values needed to make the process operate on a large scale. Somewhat higher enantioselectivities were obtained when the reaction was performed at —40°C with an N-para-methoxybenzoyl (PMB)-protected substrate 9 (Scheme 13.3). Even more important for the research concept than just enhancement of e.e.s were the observations made in these experiments. First, 2 mol of the acetylide and 2 mol of the chiral auxiliary were needed for complete ketone alkynylation. Second, pyrolidino-ephedrine 8d proved to be the best auxiliary amino-alcohol. With this auxiliary, an e.e. of over 98% was achieved, with complete conversion of the ketone, but only when the acetylide-alkoxide solution was first warmed to 0°C then cooled down to —40°C before addition of the ketone 9 (Scheme 13.3). 

Saccharin sodium produces qualitatively similar results yet is not known to be a surfactant ion [123]. At pH 7.4 NaLS has been found to increase the binding of ephedrine and quinine to rectal mucosal preparations by an unknown mechanism. It is presumed that Kakemi et al. [122] propose that the evidence of increased affinity for mucosal tissue signifies an increased concentration gradient of the drug at the interface but this is a concept that requires much more data and experimental evidence before being acceptable. The increased surface activities of the ion-pair may be a factor in increasing the interfacial concentration of the drug... 

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