Phenethyl and Phenoxypropanolamines

The phenyl ethanol amine derivatives epinephrine (U and norepinephrine ( ) are intimately associated with the sympathetic nervous system. These two neurotransmitter hor- 

As noted above, g-adrenergic agonists such as epinephrine typically cause relaxation of smooth muscle. This agent 

Acylation of ami noketone 8 with the acid chloride from p-toluic acid affords the corresponding ester (10) catalytic hydrogenation leads to the bronchodilator bitolerol (11). An analogous scheme starting from the N-methyl ketone (12) and pivaloyl chloride gives ami noalcohol (14). This compound is then resolved to isolate the levorotatory isomer. There is thus obtained the drug dipivefrin. 

A variant on this theme contains mixed acyl groups. In the absence of a specific reference it may be speculated that the synthesis starts with the diacetyl derivative (15). Controlled hydrolysis would probably give the monoacetate (16) since the ester para to the ketone should be activated by that carbonyl function. Acylation with anisoyl chloride followed by reduction would then afford nisobuterol (18). 

Catecholamines are also intimately involved in cardiac function, with 3-sympathetic agonists having a generally stimulant action on the heart. Some effort has thus been devoted to the synthesis of agents that would act selectively on the heart. (Very roughly speaking, 3 -adrenergic 

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Chapter 2. Phenethyl and Phenoxypropanolamines 1. Phenyl ethanol amines References... 

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