Synthesis enantiomers

Figure 4.6 Classical kinetic resolution with subsequent reracemization of unconverted enantiomer Synthesis of pantoic acid from pantolactone applying a stirred-tank reactor, extraction module and racemization step...

Single enantiomer synthesis is of increasing importance in pharmaceutical production. It is essential that practical and scalable procedures be developed for controlling the absolute configuration of new stereogenic centers as they are formed. Severally particularly important developments have recently been reported. 

With increasing emphasis on the single-enantiomer synthesis of pharmaceuticals, there is a need for efficient methods for the preparation of enantiomerically-enriched N and heterocycles. 

A. Vasella, Chiral building blocks in enantiomer synthesis -ex sugars, in Modem Synthetic Methods, R. Scheffold, ed., Otto Salle, Verlag, Frankfurt, 1980, p. 173. 

A racemic mixture contains equal amounts of the (+) enantiomer and the (-) enantiomer and has the designation (+/-). Racemic mixtures are not optically active, because the rotation of the dextrorotatory enantiomer cancels out the rotation of the levorotatory enantiomer. Synthesis or isolation of a single enantiomer in the laboratory is a challenging task, and most syntheses of chiral molecules result in a racemic mixture containing both enantiomers. The Food and Drug Administration (FDA) policy statement drafted in 1992 and updated in 20053 requires pharmaceutical companies to characterize the properties of single enantiomers, and this adds difficulty, time, and expense to development of new medicines. 

Asymmetric hydrogenations with transition metal catalysts have been applied to single enantiomer synthesis in the pharmaceutical industry with considerable success. ChiroTech and Pfizer developed an improved synthesis of glutarate derivative (139), an intermediate required for the synthesis of Candoxatril (140) (156). The drug, a neutral endopeptidase inhib-... 

Vasella, A, Chiral building blocks in enantiomer synthesis from sugars. In Modern Synthetic Methods, Vol. 2, Scheffold, R, Ed., Otto Salle Verlag, Frankfurt/Main, pp. 173-267, 1980. 

Vasella A (1980) Chiral building blocks in enantiomer synthesis. In Scheffold R (ed) Modem Synthetic Methods. Otto Salle Verlag GmbH Co., Frankfurt am Main, p 173... 

Table 9.3 Classification of routes for pure enantiomer synthesis... 

Prakash, Petasis and Olah used this approach to synthesize anti-a-(trifluo-romethyl)-P-amino alcohols (R = CFj) [50], and awti-o-(difluoromethyl)-P-amino alcohols (R = CF2H) (Scheme 7.9) [51, 52). An example application is the single enantiomer synthesis of anti-dif luorothreonine, which was readily obtained following N-deallylation and ozonolytic cleavage of the furan ring in the adduct 37 (R = 2-furyl,... 

Alexander, R.P., Morley, C., and Stephenson, G.R. (1988) Transition-metal mediated asymmetric synthesis. Part 6. OrganometaDic approaches to the enantiomer synthesis of tridachione a role for planar chirality in synthesis design. J. Chem. Soc. Perkin Trans. I, 2069-2074. 

Scheme 4. Enantiomer Synthesis Using Stereoselective Decarboxylation...

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