Propranolol Synthesis using

The means used to prepare these agents can be illustrated by the following examples. Practolol (109) gives less clinical bronchoconstriction in some patients than propranolol because its receptor action is more selective. Serious occasional toxicity not related to p-blockade has led to its withdrawal from clinical use. A synthesis is available which relates the absolute configuration of the more potent... 

Martinez Lagos, F., Carballeira, J.D., Bermudez, J.L. et al. (2004) Highly stereoselective reduction of haloketones using three new yeasts application to the synthesis of (S)-adrenergic beta-blockers related to propranolol. Tetrahedron Asymmetry, 15 (5), 763-770. 

Using AD mix-a or AD mix-/ as the dihydroxylation agent, various olefins can be dihydroxylated with high ee.57,67b 72 As an example, in Scheme 4-33, aryl-allyl ethers undergo dihydroxylation yielding products with good ee. The procedure can be used as an alternative for the synthesis of (2S )-propranolol.73... 

H. Sasai, T. Suzuki, N. Itoh, M. Shibasaki, Catalytic Asymmetric Synthesis of Propranolol and Metoprolol Using La-Li-BINOL Complex, Appl. Organomet. Chem... 

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. 

Liquid fluorocarbon was used as continuous phase by Perez-Moral and Mayes [19] as well. They proposed a new method for rapid synthesis of MIP beads, in that they prepared 36 polymers imprinted for propranolol and morphine with different amounts of EDMA as a cross-linker and different functional monomers (MAA, acrylic acid, hydroxyethyl methacrylate, 4-vinylpyridine) directly in SPE cartridges. The properties of MIP microspheres prepared by this method were very similar in terms of size, morphology and extent of rebinding to microspheres prepared by conventional suspension polymerisation in perfluorocarbons as well as to bulk polymers prepared in the same solvent. The most notable advantages of this method are no waste production (no transfer of beads during washing steps) and possible direct use for a variety of screening, evaluation and optimisation experiments. 

Bompart et al. [125] reported the synthesis of composite nanoparticles of approximately 500 nm diameter consisting of a polymer core, a layer of gold nanoparticles attached to the core, and a few nanometers thick MIP outer layer (Fig. 13). These particles were used as individually addressable nanosensors, where surface-enhanced Raman spectroscopy was used to detect the binding of the target analyte, the beta-antagonist propranolol. A l,000x improved detection limit was... 

A similar approach to the hydrolytic methodology uses a chromium-salen complex to open an epoxide with trimethylsilyl azide, as illustrated by the synthesis of the antihypertensive agent, (S)-propranolol (10) (Scheme 9.15).118,119... 

The p-receptor blocker propranolol is still used as a racemate, although the S enantiomer is the active compound. Devise a synthesis for this enantiomer. 

Unfortunately, the obvious starting material, allyl alcohol itself, gives an epoxide which is hard to handle, so Sharpless, who carried out this synthesis of propranolol, used this silicon-substituted allylic alcohol instead. 

Sasai, H., Itoh, N., Suzuki, T., Shibasaki, M. Catalytic asymmetric nitroaldol reaction an efficient synthesis of (S)-propranolol using the lanthanum binaphthol complex. Tetrahedron Lett. 1993, 34, 855-858. 

We return to two compounds we made earlier by the AE reaction propranolol 7 and diltiazem 67. In both cases the synthesis is easier as we do not have to start with an allylic alcohol. The synthesis of propranolol41 uses the allyl ether 188 that gives the diol 189 with good ee in the AD reaction for a monosubstituted alkene. Transformation to the epoxide 190 shows no loss of ee. Reaction with /-Pi NIE was already known to give propranolol 7. This is a very short synthesis from easily made starting materials. 

Ipodate, which inhibits the conversion of thyroxine to triiodothyronine, is useful in reducing the intensity of thyroid storm. Sympathoplegic drugs are also useful, and propranolol is the most commonly used agent. Further release of hormone from the gland is blocked by intravenous administration of sodium iodide supplemented by oral potassium iodide. Synthesis is inhibited by oral or, if necessary, parenteral antithyroid drugs. Corticosteroids are sometimes used. 

As evidenced profusely in the literature most of the drug discoveries were more or less accidental. The same was the fate in the synthesis of propranolol, for whieh a-naphthol was used in the reaetion mixture instead of the P-naphthol, as the latter was not readily available in the laboratory to arrive at the predetermined target structure as illustrated below ... 

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