Asymmetric synthesis of azolium-based 1,2,3,4-tetrahydronaphthalen-2-ols through lipase-catalyzed resolutions

Abstract

Abstract-A series of racemic trans-1,2,3,4-tetrahydronaphthalen-2-ols bearing an azole nucleus in the C-2 position has been synthesized by ring opening reaction of the corresponding epoxides using imidazole or 1,2,4-triazole. The kinetic resolution of these racemates was undertaken through transesterification processes, finding good levels of activities and high to excellent enantiodiscrimination values for the Pseudomonas cepacia lipase immobilized on a ceramic carrier. Investigations of the optimum reaction conditions were carried out by consideration of different organic solvents, temperatures, enzyme loadings and reaction times. With the best conditions on hand, the experiments were later carried out towards the resolution of the related racemic cis-alcohols, which were previously obtained through a Mitsunobu and deprotection chemical sequence from the trans-stereoisomers.--- Corresponding author.

Recent Advances in Lipase-Mediated Preparation of Pharmaceuticals and Their Intermediates

“…The experiments were performed using THF as the solvent and vinyl acetate as the acyl donor, at 30 °C and 48 h. The reaction with the rac - trans - isomer provided the trans -(2 R ,3 R )-acetate with 99% ee and trans -(2 S ,3 S )-alcohol with 93% ee , c 48% and E > 200. In the case of the rac - cis -isomer, it was obtained from the cis -(2 R ,3 S )-acetate with >99% ee and cis -(2 S ,3 R )-alcohol with 29% ee , c 23% and E > 200 ( Scheme 41 b and Table 5 ) [ 62 ]. Tetrahydronaphthylazoles are known to exhibit antileishmanial properties, which has inspired the authors [ 62 ] to resolve the racemate of trans - and cis -1-(1 H -imidazol-1-yl)-1,2,3,4-tetrahydronaphthalen-2-ols ( rac - trans - and rac - cis -1-imidazol THN) using the same aforementioned enzymatic methodology.…”

“…In the case of the rac - cis -isomer, it was obtained from the cis -(2 R ,3 S )-acetate with >99% ee and cis -(2 S ,3 R )-alcohol with 29% ee , c 23% and E > 200 ( Scheme 41 b and Table 5 ) [ 62 ]. Tetrahydronaphthylazoles are known to exhibit antileishmanial properties, which has inspired the authors [ 62 ] to resolve the racemate of trans - and cis -1-(1 H -imidazol-1-yl)-1,2,3,4-tetrahydronaphthalen-2-ols ( rac - trans - and rac - cis -1-imidazol THN) using the same aforementioned enzymatic methodology. The kinetic resolutions of these isomers were conducted in THF as a solvent and vinyl acetate as an acyl donor, at 30 °C and for 48 h. The lipases CAL-B and PSL-C I were tested and the latter led to the best results.…”

“… Enzymatic kinetic resolution of the racemic trans - and cis -3-imidazol THN ( a ); racemic trans - and cis -3-triazol THN ( b ) and racemic trans - and cis -1-imidazol THN ( c ) [ 62 ]. …”