In this report we set out to extend recent studies on
substituted PAC analogues produced by the fermentation of
aromatic aldehydes with Saccharomyces cerevisiae. The
medium selected contained glucose as a carbon source for
the biotransformation, and sodium pyruvate as an inhibitor
for alcohol dehydrogenase, the enzyme responsible for the
conversion of the carbinol to a benzyl alcohol derivatives.
An investigation of sodium cyanoborohydride for a selective
reductive amination was carried out on these carbinols to
produce the corresponding ephedrine analogues. Poor
selectivity was apparent for this reagent but when the
reduction products were converted to their hydrochloride
derivatives the optically pure compounds separated readily
by fractional crystallisation. Their pharmacological
activity was investigated using commercial ephedrine as a
reference compound. The synthesised (-) ephedrine had an
identical activity to the commercial compound, while the
substituted analogues all had a slightly lower activity,
with the exception of (-)-4-chloro ephedrine which showed
a stronger antispasmodic effect. The stereoselectivity of
the synthesis and the enantiomeric purity of the resolved
compounds were investigated by high field nuclear magnetic
resonance spectrometry employing chiral praseodymium shift
reagents .