| dc.description.abstract | Beta blockers are medications used to reduce blood pressure. In commercial beta blockers, the active pharmaceutical ingredient (API) is always a chiral molecule, and is usually present as a racemic mixture. Usually, one enantiomer of the API, called the eutomer, has most of the beta-blocking properties, while the other can be responsible for unwanted side effects. This thesis concerns the chemo-enzymatic synthesis of enantiopure (R)-sotalol, (S)-penbutolol and (S)-bisoprolol, the eutomers of the beta-blockers sotalol, penbutolol and bisoprolol. The aim was to synthesize them and their precursors in an environmentally friendly and efficient way, and with an enantiomeric excess of at least 96%.
(R)-Sotalol precursor (R)-N-(4-(2-chloro-1-hydroxyethyl)phenyl)methanesulfonamide was synthesized from aniline in three steps with a combined yield of 53%. The product had an ee of 81%.
(S)-Penbutolol hydrochloride was obtained from 2-cyclopentylphenol in five steps with a combined yield of 20%. The product had an ee of 99%.
(S)-Bisoprolol hemifumarate was synthesized from 4-(hydroxymethyl)phenol in six steps with a combined yield of 19%. The product had an ee of more than 96%. | |
