Preparation of novel meta- and para-substituted N-benzyl protected quinuclidine esters and their resolution with butyrylcholinesterase

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.     

On the centralizer and the commutator subgroup of an automorphism

Let φ be an automorphism of a group G. In this paper, we study the influence of its centralizer \({C_G(\varphi)}\) on its commutator subgroup \({[G,\varphi]}\) when G is polycyclic or metabelian. For instance, when G is metabelian and φ fixed-point-free of prime order p, we prove that \({[G,\varphi]}\) is nilpotent of class ≤ p. Also, when G is polycyclic and φ of order 2, we show that if \({C_G(\varphi)}\) is finite, then so are \({G/[G,\varphi]}\) and \({[G,\varphi]'}\) .