Lipase catalyzed kinetic resolution of rac-2-phenylpropan-1-ol derivatives as building block for phenolic sesquiterpenes

Highly enantioselective and enantiospecific resolution processes were developed for 2-(3-methoxy-4-methyl-phenyl)-propan-1-ol (VI), 2-(2-methoxy-5-methyl-phenyl)-propan-1-ol (VII), 2-(3,4,5-trimethoxy-phenyl)-propan-1-ol (VIII) and 2-(3-hydroxy-4-methyl-phenyl)-propan-1-ol (XII) via lipase-catalyzed transesterification and hydrolysis using vinyl propionate as acylating agent. The general procedure for synthesis and kinetic resolution of 2-phenylpropan-1-ol derivatives would be beneficial for getting chiral building block of bisabolane types of natural and unnatural sesquiterpenes. Gallic acid moiety was diversified with a chiral center at the benzylic position and subsequent resolution process gave resolved isomers with higher enantiopurity. Both isomers were separated with ee of at least 95%. Enantioselectivity, E was even higher up to 316 during the process. These resolved chiral intermediates will facilitate the commercial synthesis of bio-active natural and unnatural xanthorrhizol, elvirol and gallate derivatives.

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► The study covers the synthesis and resolution process of phenolic esters and alcohols containing a chiral center at the benzylic position.
► The resolved alcohols are essential building block of natural and unnatural synthetic sesquiterpenes and sesquiterpenoides.
► Among several lipases, CAL-B showed higher enantioselectivity up to (E = 316).
► The diversified chiral gallic acid moiety will open the opportunity to get optimized biological active compounds for food and pharmaceutical industry.