Growth optical isomers

The cell growth inhibition data confirmed that, of the optically active (3-lactam, 66 and 58 were extremely active (obtained from two different pathways), and the activity of the other optical isomer 68 and 59 (obtained from two different pathways) was reduced compared to the racemic (3-lactam 1. 

A primary example is the resolution of optical isomers by continuous crystallization in fluid beds. Control of low supersaturation by control of the temperature difference between the continuous feed and the seed bed is critical to maintaining an essentially all-growth regime in which the individual isomers grow on their respective seeds in separate crystalfi-zers. The seed beds in both crystallizers are massive in relation to the amount of racemic solution passing through in order to present sufficient seed area to maintain low supersaturation. Uncrystallized isomers in the overhead streams are recycled to dissolve additional racemic feed. Crystal size is maintained by sonication. See Examples 7-6 and L1-6 for a discussion of resolution of optical isomers by continuous crystallization. 

Massive (the seed is the product in a continuous or semicontinuous operation), to provide maximum opportunity for aU growth. (See Examples 7-6 and 11-6 on resolution of optical isomers.)... 

The most effective seeding is achieved in semicontinuous and continuous crystallizations by the nature of the operations themselves, in which the seed is always present and in large quantity. Although common in large industrial operations, these techniques have found more limited application in the pharmaceutical industry. Exceptions to this are detailed in Examples 7-6 and 11-6, on the continuous resolution of optical isomers in fluid bed crystal-fizers, and in Example 10-1, which presents a semicontinuous method of utilizing seed heel recycle in reactive crystallization to achieve primarily growth. 

Bauer, C. D. and Berg, C. P., The amino acids required for growth in mice and the availability of their optical isomer, /. Nutr., 26, 51, 1943. 

A particularly interesting use of seeds is in the resolution of the isomers of methy l-dopa as practiced by Merck Co., Inc. In this process two fluidized beds operate in tandem, each of which is seeded with one of the optical isomers. Supersaturation is controlled to minimize nucleation so that growth of each isomer occurs on the existing crystals in their respective beds (see Section... 

The second important observation on stereoisomer separation also involved ammonium sodium tartrate. Thirty-four years after Pasteur s observation, Jungfleisch (1882) observed that carefully introducing crystals of the individual isomers into different areas of a supersaturated solution of ammonium sodium tartrate resulted in the growth of isomerically pure crystals. These two observations form the basis for most industrial scale crystallizations for the purification of enantiomers or diastereoi-somers. However, it is more common for a solute to crystallize with the thermodynamically stable crystal form being a compound of the two isomers. This is typically denoted as a racemic compound. Secor (1963) made the first systematic review of optical isomer separation by crystallization, based upon phase behavior. Collet, Brienne, and Jacques (1980) applied systematic thermodynamics to the phase behavior, and developed straightforward methods for correlating the solubilities of isomers. 

Many agents, which are biologically highly active but lack the molecular structure necessary for optical isomerism, display differences in activity between isomers once the possibility of isomerism is introduced. Thus the auxin types of plant-growth regulators usually lack an asymmetric carbon atom and hence are incapable of furnishing pairs of optical isomers. However, when an... 

This compound was first isolated from milk concentrates in two forms differing very significantly in their optical rotation. The dextrorotatory compound was found to be. a highly active growth factor for Saccharomyces cerevisiae (as active as biotin) whereas the levorotatory isomer showed hardly any activity ". The oxidation of biotin with one mole of hydrogen peroxide also yielded both forms which were separated by crystallization and were called [Pg.83]

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