Prenalterol exhibits adrenergic agonist activity 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
monobenzone (2) with the epoxide derived from α-D-
glucofuranose[4] affords the glycosylated derivative (3). Hydrolytic removal of the
acetonide protecting groups[5] 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).
^DE 2503968, Jaeggi KA, Schröter H, Ostermayer F, "Optisch aktive Derivate des 1-Phenoxy-2-hydroxy-3-aminopropan und Verfahren zu ihrer Herstellung [Optically active derivatives of 1-phenoxy-2-hydroxy-3-aminopropane and the process for their production]", published 1975-08-14, assigned to
Ciba-Geigy AG Chem. Abstr. 84, 5322 (1976).