Synthesis of enantiomers of exo‐2‐norbornyl‐N‐n‐butylcarbamate and endo‐2‐norbornyl‐N‐n‐butylcarbamate for stereoselective inhibition of acetylcholinesterase

Abstract

The acetylcholinesterase inhibition by enantiomers of exo- and endo-2-norbornyl-N-n-butylcarbamates shows high stereoselelectivity. For the acetylcholinesterase inhibitions by (R)-(+)- and (S)-(-)-exo-2-norbornyl-N-n-butylcarbamates, the R-enantiomer is more potent than the S-enantiomer. But, for the acetylcholinesterase inhibitions by (R)-(+)- and (S)-(-)-endo-2-norbornyl-N-n-butylcarbamates, the S-enantiomer is more potent than the R-enantiomer. Optically pure (R)-(+)-exo-, (S)-(-)-exo-, (R)-(+)-endo-, and (S)-(-)-endo-2-norbornyl-N-n-butylcarbamates are synthesized from condensations of optically pure (R)-(+)-exo-, (S)-(-)-exo-, (R)-(+)-endo-, and (S)-(-)-endo-2-norborneols with n-butyl isocyanate, respectively. Optically pure norborneols are obtained from kinetic resolutions of their racemic esters by lipase catalysis in organic solvent.

Stereo‐specific inhibition of acetyl‐ and butyryl‐cholinesterases by enantiomers of cis,cis‐decahydro‐2‐naphthyl‐N‐n‐butylcarbamate

“…This stereopreference (R > S) is the same with that for the inhibition by enantiomers of exo-2-norbornyl-N-n-butylcarbamate but is opposite to that for the inhibition by enantiomers of endo-2-norbornyl-N-n-butylcarbamate [17].…”

“…(2S,4aR,8aS)-cis,cis-, (2R,4aS,8aR)-cis,cis-, racemic cis,cis-, and racemic trans,cis-decahydro-2-naphthyl-Nn-butylcarbamates (Figure 1) are all characterized as pseudosubstrate inhibitors of AChE and BChE (Eq. (1), Figure 2, Tables 2 and 3) [8][9][10][11][12][13][14][15]17,19,[27][28][29][30].…”

“…The stereospecificity of AChE plays an important role in many Alzheimer's disease drug such as Rivastigmine, Physostigmine, and Huperzine-A ( Figure 1). We have reported that AChE has shown stereo-specific inhibition for stereoisomers of 1,1 -bi-2-naphthyl-di-N-n-butylcarbamate [16] and exo-and endo-2-norbornyl-N-n-butylcarbamates [17]. BChE has also shown stereo-specific inhibition by enantiomers of isomalathion [18], exoand endo-2-norbornyl-N-n-butylcarbamates [19].…”

Synthesis and Evaluation of Two Coumarin‐Type Derivatization Reagents for Fluorescence Detection of Chiral Amines and Chiral Carboxylic Acids

“…An amine functionality for the derivatization has been also used in luminarin 4, a achiral coumarin labeling reagent for carboxylic acids . Compound 4 can be considered as a candidate for further investigation on enantioselective inhibition of cholinesterases …”

“…14 Compound 4 can be considered as a candidate for further investigation on enantioselective inhibition of cholinesterases. 28 For the design of the other reagent, lactate was chosen as the chiral recognition site to be introduced into the coumarin core. A similar strategy was followed to construct chiral derivatizing agents for 1 H NMR inspection.…”