Albuterol synthesis

Although very efficient, the broad application of the direct preparation is restricted due to the limited number of pure starting enantiomers. The design of a multistep process that includes asymmetric synthesis is cumbersome and the development costs may be quite high. This approach is likely best suited for the multi-ton scale production of commodity enantiomers such as the drugs ibuprofen, naproxen, atenolol, and albuterol. However, even the best asymmetric syntheses do not lead to products in an enantiomerically pure state (100 % enantiomeric excess). Typically, the product is enriched to a certain degree with one enantiomer. Therefore, an additional purification step may be needed to achieve the required enantiopurity. 

P. Chetoni, P. Crotti, M. F. Saettone, Albuterol Prodrugs for Ocular Administration Synthesis and Evaluation of the Physicochemical and IOP-Depressant Properties of Three Albuterol Triesters , Int. J. Pharm. 1994, 105, 147-155. 

SCHEME 2. Proposed new synthesis of ketoaldehyde hydrate for albuterol. 

The reaction of epoxide rings with nucleophiles is important for the synthesis of many biologically active compounds, including albuterol and salmeterol, two bronchodilators used in the treatment of asthma (Figure 9.10). 

Devise a synthesis of the bronchodilator albuterol from the given starting material. 

Figure 9-8. A synthesis of albuterol (Salbutamol). Adopted from several sources. Fries rearrangement with (-) p-ditoluyltartarric acid, -butylamine afforded poor results. ePh = phenyl.

SCHEME 25.8 Microwave-assisted total synthesis of Albuterol. 

Microwave dielectric heating was thus used for the total synthesis of albuterol in 62% overall isolated yield compared to 43% reported conventionally. The total synthesis time was also significantly reduced from the conventional 47 h to 40 min. 

Chemists have developed several syntheses for the antiasthmatic drug albuterol (Proventil). One of these syntheses starts with salicylic acid, the same acid that is the starting material for the synthesis of aspirin ... 

Following is a synthesis for albuterol (Proventil), currently one of the most widely used inhalation bronchodilators. 

Devise a synthesis of each compound from the given starting material(s). Albuterol is a bronchodilator and proparacaine is a local anesthetic. 

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