Propranolol synthesis

The products of a Sharpless epoxidation, such as epoxides 12, 16, or 22, are potentially unstable in base as the anion of the alcohol can attack the epoxide 24 in the Payne rearrangement. This is easily seen with the simplest compound 12. It doesn t and we have rather given the game away by the compound numbers. The OH groups in the right hand and in the left hand compounds 12 are homotopic. Sharpless made the definitive statement of this in his propranolol synthesis.6... 

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. 

Scheme 3-63 gives another example in which an asymmetric Henry reaction is involved in the synthesis of the /i-receptor-blocking drug (S )-propranolol. 

Scheme 4-33. Asymmetric dihydroxylation as a key step in the synthesis of (2S) -propranolol.

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... 

Progesterone, 164 Proglumide, 93 Propanidid, 79 Propenzolate, 75 Propizepine, 472 Propoxyphene, 57 Propranolol, 105, 107, 212 Proquazone, 386 Proquinolate, 368 Prorenone, 175 Prostalene, 5 Proxazole, 271 Purine synthesis, 467 Psilocybine, 342 Psychotomimetic activity, 71... 

Propranolol The synthesis of propranolol, l-isopropylamino-3-(l-napthyloxy)propan-2-ol (12.1.3) is described in Chapter 12. 

Propranolol Propranolol is l-(/xo-propylamino)-3-(l-naphthoxy)-2-propanol (12.1.2). The synthesis of this drug is described in Chapter 12. 

W. M. Mullett, P. Martin, and J. Pawliszyn, In-Tube Molecularly Imprinted Polymer Solid-Phase Microextraction for the Selective Determination of Propranolol, Anal. Chem. 2001, 73, 2383 N. Masque, R. M. Marce, F. Borrull, P. A. G. Cormack, and D. C. Sherrington, Synthesis and Evaluation of a Molecularly Imprinted Polymer for Solid-Phase Extraction of 4-Nitrophenol from Environmental Water, Anal. Chem. 2000, 72, 4122. 

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. 

---