P-Adrenergic blocking agents synthesis

The advantages of the catalyzed version are particularly apparent in the case of allyl alcohol whose epoxide, glycidol (2), is unstable to the catalyst.2 It can be obtained by catalyzed epoxidation at 0° with cumene hydroperoxide instead of t-butyl hydroperoxide in 65% yield and 90% ee. However, for use in a synthesis of the P-adrenergic blocking agent (2S)-propranolol (5), the epoxide is not isolated but treated with sodium a-naphthoxide to furnish the diol 3. The synthesis of 5 is completed by conversion to an epoxide (4) and ring opening with isopropylamine. 

Figure 26 Synthesis of chiral synthon for P-adrenergic blocking agent Stereoselective enzymatic hydrolysis of racemic 87.

Besides Pseudomonas oleovorans numerous bacteria have been shown to epox-idize alkenes [1167, 1168]. As shown in Scheme 2.155, the optical purity of epoxides depends on the strain used, although the absolute configuration is usually R) [1169]. This concept has been recently applied to the synthesis of chiral alkyl and aryl gycidyl ethers [ 1170,1171], The latter are of interest for the preparation of enantiopure 3-substituted l-alkylamino-2-propanols, which are widely used as p-adrenergic receptor-blocking agents [1172],... 

Bufuralol is a nonselective (3-adrenoreceptor blocking agent of comparable potency to propranolol. It has proven to be effective in treating hypertension and is a potent nonselective p-adrenergic receptor antagonist. Similarly to the method described earlier in Scheme 57.9, an efficient chemoenzymatic synthesis of (/ )-bufuralol has been reported involving a DKR of the chlorohydrin key intermediate rac-44 (Scheme 57.10). ... 

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