Ester ammoniolysis: a new enzymatic reaction

Abstract

A new enzymatic reaction of carboxylic esters and ammonia (ammoniolysis) provides a synthetically useful and mild procedure for the enantioselective synthesis of amides.

Lipase and esterase-catalyzed acylation of hetero-substituted nitrogen nucleophiles in water and organic solvents

“…In nearly anhydrous medium (using NH 2 OH и HCl and triethyl amine, data not shown) no reaction was observed at all with any of the enzymes apart from a small amount of hydrolysis. The inability to acylate hydroxylamine in the absence of water is rather surprising because, e.g., C. antarctica lipase B (Novozym 435) is known to be active at very low water activity in ammoniolysis (De Zoete et al, 1993, 1994a, 1995 as well as in transesterification (Woudenberg-van Oosterom et al, 1996). The initial reaction rate, using C. antarctica lipase B and 0.5 M hydroxylamine, increased with the water concentration and peaked at 1.75 M water (data not shown).…”

“…The initial experiments were performed with ethyl octanoate and hydroxylamine in tert-butyl alcohol, which was known to be a good solvent for enzymatic ester ammoniolysis (De Zoete et al, 1993, 1994. The lipases that had previously shown activity in the ammoniolysis reaction were also active in the hydroxylaminolysis reaction provided that a small amount of water was present.…”

“…For example, carbohydrates (Woudenberg, et al, 1996), alkyl amines (Quiros et al, 1993;Zaks and Klibanov, 1985), ammonia (De Zoete et al, 1993, 1994a, 1995a,b, 1996Garcia et al, 1993), and hydrogen peroxide (Björkling et al, 1990(Björkling et al, , 1992 have been successfully used as acyl acceptors.…”

Fully Enzymatic Resolution of Chiral Amines: Acylation and Deacylation in the Presence of Candida antarctica Lipase B

“…Presumably, improved hydrolysis rates could result from appropriate mutagenesis. [26] Hydrolysis of racemic 5b in the presence of CaLB showed negligible enantiodiscrimination, which indicates that the rate-determining steps in synthesis and hydrolysis are different, [27] and the issue was not pursued any further. Enantiomerically pure (R)-1 and (R)-2 were obtained, nevertheless, on account of the good enantioselectivities in the acylations.…”

6.11 N-Acylation Reactions of Amines

“…136 Representative examples, where this lipase has been used for amide synthesis, include its use for the ammonolysis of triacylglycerols (Figure 31(a)), 137 synthesis of a hindered pyrrole-amide as a drug intermediate (Figure 31(b)), 138 and for the regioselective amidation of diester substrates to selectively afford monoamide esters (Figure 31(c)). 139 …”