The effect of substrate structure on the chemoselectivity of Candida 1 antarctica lipase B - catalyzed acylation of amino - alcohols 2

12 The selective acylation of multifunctional compounds exhibiting both alcohol and amino 13 groups gives interesting products with many applications in food, cosmetic and 14 pharmaceutical industries, but it is real challenge. The current work describes the different 15 behavior shown by Candida antarctica lipase B (Novozym 435) when catalyzing the O-16 acylation and N-acylation of bifunctional acyl acceptors. The acylation of three amino-17 alcohols (alaninol, 4-amino-1-pentanol and 6-amino-1-hexanol) was studied using myristic 18 acid as an acyl donor. To achieve this, a structure-reactivity study was performed in tert-amyl 19 alcohol as a solvent, comparing the three amino-alcohols as acyl acceptors and a series of 20 structurally related amines, namely (R)-sec-butylamine, 1-methoxy-2-propylamine and 1,2-21 diaminopropane. These substrates were designed to investigate the effect of the group located 22 in β-position of the amino group on the acyl acceptor: the more nucleophilic the group, the 23 more the apparent maximal velocity (V max,app) of N-acylation increases. Moreover, the crucial 24 role of the carbon chain length between the alcohol and amino groups on the chemoselectivity 25 was also demonstrated. The chemoselectivity for the N-acylation was improved when the 26 carbon chain included two carbons (alaninol) whereas the chemoselectivity for the O-27 acylation was improved when the carbon chain included four carbons or more (4-amino-1-28 pentanol and 6-amino-1-hexanol). 29 These results provided new insights for the selective synthesis of amides or esters produced 30 from the acylation of bifunctional substrates.