The invention belongs to the technical field of
medicine, and discloses a preparation method of (3S,2'S), (3S,2'R), (3R,2'R) and (3R,2'S) four type chiral monomers of muscarine
receptor antagonist racemic
medicine glycopyrronium bromide. The method comprises the following steps: resolving racemic alpha-cyclopentylmandelic acid by a chemical resolution method by using L-
Tyrosine methyl ester and (R)-alpha-phenylethylamine as resolution reagents to respectively prepare (S)-alpha-cyclopentylmandelic acid and (R)-alpha-cyclopentylmandelic acid; and carrying out
esterification reaction to respectively obtain chiral intermediates (S) / (R)-alpha-cyclopentylmethyl mandelate. L / D-
malic acid used as the
raw material is subjected to four reaction steps, including condensation,
carbonyl reduction,
catalytic hydrogenation or
transfer hydrogenation reduction debenzylation, and reduction
alkylation or alkylogen
alkylation, in a chiral synthesis mode to obtain another important chiral intermediate (S) / (R)-N-methyl-3-hydroxypyrrolidine. The chiral intermediate is subjected to ester exchange and quaterisation to respectively obtain the four (3S,2'S), (3S,2'R), (3R,2'R) and (3R,2'S) type
glycopyrronium bromide chiral monomers. The result indicates that the (3R,2'S)-
glycopyrronium bromide has the strongest
cholinergic antagonistic action.