Resolving agents enzymes

The initial concentration of the solution was 10.0 g of ( )-(62) in 50 g of acetone. In all runs, 10 mg of seed crystals were used. From the 10 runs highlighted in the 18.1, 21.0 g of /2-(-)-(62) of >92.0% ee and 21.4 g of (jS)-(+)-(62) of >90% ee are obtained from an input of 50.4 g of racemate. The table also nicely illustrates the continuous nature of the process, which coupled with the fact that no resolving agent, chiral auxiliary, enzyme, or catalyst is needed, underlines the economic advantages of this type of process. 

In this instance, the exact proportions of the resolving agent and 8 and the purity of the crystallisation solvent were important in getting good results.3 After one crystallisation, the ee of the salt was about 50% but this improved by 10-15% with each recrystallisation and reached >99% after five recrystallisations. By then the yield had dropped to 30% from a theoretical maximum of 50%. For the next stage in their synthesis, they really needed the Boc derivative (5)-(+)-10 so the salt was directly converted to 10 in >99% ee on a 50 g scale. You will see later in this chapter that an enzyme can be used to do the same resolution. 

Numerous racemates have been separated into their enantiomers since the first success in 1848 by Pasteur. The traditional method is to derivatize a racemate into a mixture of two diastereoisomers by means of so-called resolving agents, and then to separate the diastereoisomers by recrystallization or chromatography. Recent development of chiral stationary phases for chromatographic separation of the enantiomers made it possible to separate them even without derivatization. Another method of choice is to use enzymes for enantiomer separation. Examples in this chapter will illustrate the use of these methods. After enantiomer separation, the absolute configuration and the enantiomeric purity of the resulting enantiomers must be determined. 

Enzymes are also used as resolving agents because of their ability to catalyze a reaction of one enantiomer but not that of its mirror image. 

The resolutions described above are based on the formation of diaste-reomeric complexes with a column stationary phase or an enzyme. The more common alternative is to bond the enantiomers covalently to a chiral resolving agent to make stable diastereomeric molecules, separate those diastereomers by chromatography or recrystallization, and then disassemble each purified diastereomer to obtain the resolved enantiomers. 

A number of 1- and 2-aminophosphonates were resolved by a straight CAL-B-promoted acetylation of the amino group in the substrates rac-SS. Surprisingly, ethyl acetate had to be used as an acetylating agent, since the commonly applied vinyl acetate reacted with aminoalkanephosphonates even in the absence of an enzyme (Equation 30, Table 6). ... 

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Efficient kinetic resolution of chiral unsaturated secondary alcohols by irreversible enzyme-mediated acylation (with vinyl acetate as acylating agent, a crude preparation of Pseudomonas AK, and hexane as solvent) is possible, provided one relatively large and one small substituent are attached to the carbinol carbon. However, the method can be used to resolve substrates that are not amenable to asymmetric epoxidation (see examples 23, 25, 27, 29, where the double bond is either deactivated by an electron-withdrawing substituent, or is of the propargyl alcohol type). Acylation of the / -enantiomer consistently proceeds faster than that of the 5-enantiomer. An example of an allenic alcohol was also reported248. 

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