Prenalterol

Prenalterol is a cardiac stimulant which acts as a β₁-adrenergic agonist.

Synthesis

Stereospecific

Prenalterol interestingly exhibits adrenergic agonist acitivity in spite of an interposed oxymethylene group. The stereospecific synthesis devised for this molecule relies on the fact that the side chain is very similar in oxidation state to that of a sugar.

Condensation of the monobenzyl ether of phenol 1 with the epoxide derived from α-D-Glucofuranose affords the glycosylated derivative (3). Hydrolytic removal of the acetonide protecting groups (cf. eg) followed by cleavage of the sugar with periodate gives aldehyde (4). This is reduced to the glycol by means of NaBH4 and the terminal alcohol is converted to the mesylate (5). Displacement of the leaving group with isopropylamine followed by hydrogenolytic removal of the O-benzyl ether affords the β₁-adrenergic selective adrenergic agonist prenalterol (6).

Racemic

Prepns of the racemic mixture: NL 6409883  corresp to H. Köppe et al., U.S. Patent 3,637,852 (1965, 1972 both to Boehringer Ingelheim); NL 301580  corresp to A. F. Crowther, L. H. Smith, U.S. Patent 3,501,769 (1965, 1970 both to ICI);