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Molecules 2012, 17(1), 786-795; doi:10.3390/molecules17010786
Article

Preparation of Novel meta- and para-Substituted N-Benzyl Protected Quinuclidine Esters and Their Resolution with Butyrylcholinesterase

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Received: 8 December 2011; in revised form: 5 January 2012 / Accepted: 11 January 2012 / Published: 16 January 2012
(This article belongs to the Special Issue ECSOC-15)
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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.
Keywords: quinuclidin-3-ol; esters, resolution; butyrylcholinesterase; N-benzyl protected groups quinuclidin-3-ol; esters, resolution; butyrylcholinesterase; N-benzyl protected groups
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Primožič, I.; Bolant, M.; Ramić, A.; Tomić, S. Preparation of Novel meta- and para-Substituted N-Benzyl Protected Quinuclidine Esters and Their Resolution with Butyrylcholinesterase. Molecules 2012, 17, 786-795.

AMA Style

Primožič I, Bolant M, Ramić A, Tomić S. Preparation of Novel meta- and para-Substituted N-Benzyl Protected Quinuclidine Esters and Their Resolution with Butyrylcholinesterase. Molecules. 2012; 17(1):786-795.

Chicago/Turabian Style

Primožič, Ines; Bolant, Marijana; Ramić, Alma; Tomić, Srđanka. 2012. "Preparation of Novel meta- and para-Substituted N-Benzyl Protected Quinuclidine Esters and Their Resolution with Butyrylcholinesterase." Molecules 17, no. 1: 786-795.



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