Enantiopure synthesis of 7-(1-pyrindanyl)propargyl ethers as rasagiline analogues via chemical or enzymatic resolution of 1-pyrindan-7-ol?

RSC Advances Pub Date: 2015-12-07 DOI: 10.1039/C5RA24868J

Abstract

In this work, the enantiopure synthesis of 7-(1-pyrindanyl)propargyl ethers – rasagiline analogues – via chemical and/or enzymatic resolution of the racemic precursor 1-pyrindan-7-ol is described. (R)-Methoxyphenylacetic acid – (R)-MPAA – and (S)-methoxyphenylacetic acid – (S)-MPAA were used as chemical resolution agents, whereas Candida antarctica lipase B (CALB) was employed as kinetic resolution catalyst. The enzymatic resolution was successfully achieved by two different approaches: (1) transesterification of racemic 1-pyrindan-7-ol, which was found to selectively acylate the (R)-enantiomer with high efficiency; (2) hydrolysis of the racemic 7-(1-pyrindanyl)acetate, which was also highly selective to the (R)-enantiomer. The enzymatic hydrolysis was performed in a non-aqueous solvent using a lipase with significant absorbed water content. The configuration of the two enantiomers of 1-pyrindan-7-ol (and consequently of the 7-(1-pyrindanyl)propargyl ethers) were unequivocally determined by X-ray crystallography and/or specific optical rotation.

Graphical abstract: Enantiopure synthesis of 7-(1-pyrindanyl)propargyl ethers as rasagiline analogues via chemical or enzymatic resolution of 1-pyrindan-7-ol
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