title: Preparation of novel meta- and para-substituted N-benzyl protected quinuclidine esters and their resolution with butyrylcholinesterase.
abstract: Since the optically active quinuclidin-3-ol is an important intermediate in the preparation of physiologically or pharmacologically active compounds, a new biocatalytic method for the production of chiral quinuclidin-3-ols was examined. Butyrylcholinesterase (BChE; EC 3.1.1.8) was chosen as a biocatalyst in a preparative kinetic resolution of enantiomers. A series of racemic, (R)- and (S)-esters of quinuclidin-3-ol and acetic, benzoic, phthalic and isonicotinic acids were synthesized, as well as their racemic quaternary N-benzyl, meta- and para-N-bromo and N-methylbenzyl derivatives. After the resolution, all N-benzyl protected groups were successfully removed by catalytic transfer hydrogenation with ammonium formate (10% Pd-C). Hydrolyses studies with BChE confirmed that (R)-enantiomers of the prepared esters are much better substrates for the enzyme than (S)-enantiomers. Introduction of bromine atom or methyl group in the meta or para position of the benzyl moiety resulted in a considerable improvement of the stereoselectivity compared to the non-substituted compounds. Optically pure quinuclidin-3-ols were prepared in high yields and enantiopurity by the usage of various N-benzyl protected groups and BChE as a biocatalyst.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102A, HR-10 000 Zagreb, Croatia. ines.primozic@chem.pmf.hr
authors.forename: Ines
authors.initials: I
authors.lastname: Primožič
authors.forename: Marijana
authors.initials: M
authors.lastname: Bolant
authors.forename: Alma
authors.initials: A
authors.lastname: Ramić
authors.forename: Srđanka
authors.initials: S
authors.lastname: Tomić
mesh_terms: D055162:Biocatalysis; D002091:Butyrylcholinesterase / Q000737:chemistry*; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D005561:Formates / Q000737:chemistry; D006865:Hydrogenation; D006868:Hydrolysis; D011812:Quinuclidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D013237:Stereoisomerism
chemical_list: D004952:Esters; D005561:Formates; D011812:Quinuclidines; C030544:formic acid; D002091:Butyrylcholinesterase