Enzymatic deracemization of halogenated dihydroindenols and dihydroindenediols substituted in benzene ring

Abstract

The optically active halodihydroindenols and dihydroindenediols are components of many biologically active natural compounds. They attract close attention as synthetic blocks for the construction of important pharmaceutical preparations, peptide nucleic acids, and bioregulators. For example, indinavir is an oral drug used to treat human immunodeficiency virus infection [1]. This protease inhibitor, a highly active antiretroviral therapy product, is used to treat HIV infection and AIDS. Cis-and trans-indanediols are the key chiral synthones in the synthesis of indinavir 1 (Scheme 1) [2-4]. Therefore, the chiral derivatives of indanes attract great interest of many chemists, and various approaches to their preparation were developed. Some chiral de rivatives of indanes are produced in industry. For example, in the industrial method for producing the chiral synthetic block indinavir-(1S,2R)-cis-aminoindanol, the bacterial cells of Rhodocco

Сonvergent method for the determination of the absolute configurations of 2,3-dihydro-1H-inden-1-ols

“…Thus, in accordance with the structure of active center, the orientation of the secondary alcohol occurs during the esterification and hydrolysis of corresponding esters. 14,15,16 Resolution of halo-2,3-dihydroinden-1-ols into enantiomers was carried out by acylation with vinyl acetate under kinetic control conditions in the presence of Burkholderia cepacia lipase. The reaction was brought to 50% conversion, then the reaction was stopped by filtration of the biocatalyst.…”

“…Under optimal conditions, the treatment of acetates 3a-16a with Novozyme 435® in dibutyl ether for 30 hours at 40 °C led to the conversion of (rac)-acetate to (R)-halo-2,3-dihydro-1H-inden-1-ol 3-16 in yield 49% and with 92% ee, respectively. 16 OAc CALB/pH 7.2…”