1,2-Amino alcohols from epoxides, with resolution

Coke and Richon have constructed the 8-lactone framework of n-hexadecalactone, the proposed pheromone isolated from Vespa orientalis, through lactonization of a hydroxy acid intermediate [39] (Scheme 3). The optically pure amino alcohol 22 obtained by resolution was converted to the optically active epoxide 23 by quatemization, followed by Hofmaim elimination. Addition of the dianion of propiolic acid to epoxide 23, and subsequent reduction of the resulting acetylenic hydroxy acid with hydrogen and palladium, provided the saturated hydroxy acid 25, which spontaneously cycUzed to afford 8-lactone 12. In a similar way, the enantiomer of amino alcohol 22 was also transformed into the antipode of lactone 12. Furthermore, using this method, any terminal epoxide can easily be converted to the corresponding saturated 8-lactone in two steps. 

In Chapter 7, we briefly mentioned that there were a number of biological methods for resolution of racemic mixtures of chiral compounds. Because enzymes, biological catalysts, are composed of chiral amino acids, they will generally accept only the natural enantiomer of a compound as their substrate. Some enzymes are very specific as to their substrate, but others can be used with whole classes of substrate, even where these are not very close in overall structure to their natural substrates. The simplest form of resolution involves a racemate, where one enantiomer is transformed by the enzyme and the other is not. This is called kinetic resolution, since it depends on the relative rates of enzymatic catalysis of the reactions of one enantiomer over the other. Our first example is shown in Figure 15.22. When the epoxide is opened by the Grignard reagent, only the tra s-product is formed, but this is a racemic mixture. The alcohol is converted to an ester, which is then hydrolyzed enzymatically using a lipase enzyme from Pseudomonas fluorescens. Notice the very mild conditions for... 

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