The control of Novozym® 435 chemoselectivity and specificity by the solvents in acylation reactions of amino-alcohols

Florian Le Joubioux (1) , Nicolas Bridiau (1) , Yesmine Ben Henda (1) , Oussama Achour (1) , Marianne Graber (1) , Thierry Maugard (1)

1 LIENSs - LIttoral ENvironnement et Sociétés

The current work describes the differential behaviour of Novozym® 435 (immobilized Candida antarctica lipase B) in O-acylation and N-acylation catalysis of bifunctional amino-alcohols acyl acceptors. We performed acylation experiments on three amino-alcohols (alaninol, 4-amino-1-pentanol and 6-amino- 1-hexanol) using myristic acid as an acyl donor. Two organic solvents (tert-amyl alcohol and n-hexane) and one ionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate: Bmim [PF6]) were used to determine the effect of the solvent. The influence of the amino-alcohol carbon chain length between the alcohol and amino groups on chemoselectivity C (kcat,app O-acylation/kcat,app N-acylation) was highlighted. N-acylation is improved using alaninol, a short chain amino-alcohol (no mono-O-acylation in tert-amyl alcohol and C = 0.12 in n-hexane) whereas O-acylation is improved using 4-amino-1-pentanol and 6- amino-1-hexanol which are amino-alcohols with longer chain (C = 10.5 in tert-amyl alcohol and C = 539 in n-hexane). On the other hand, the production of the acylated amino-alcohols after 96 h of reaction was shown to be strongly affected by the solvent nature and the amino-alcohol structure: starting from alaninol as an acyl acceptor, the yield of amide synthesis reaches up to 98% in tert-amyl alcohol using 0.7 equivalents of myristic acid while the yield of amido-ester synthesis reaches up to 88% in Bmim [PF6] using 1.75 equivalents of myristic acid.

Domaines: Biotechnologies; Biotechnologie

Florian Le Joubioux, Nicolas Bridiau, Yesmine Ben Henda, Oussama Achour, Marianne Graber, et al.. The control of Novozym® 435 chemoselectivity and specificity by the solvents in acylation reactions of amino-alcohols. Journal of Molecular Catalysis B: Enzymatic, 2013, 95, pp.99-110. ⟨10.1016/j.molcatb.2013.06.002⟩. ⟨hal-01070399⟩