Francisca Rebolledo

Enzymatic aminolysis and transamidation reactions

Abstract Chiral amides obtained from (±)-2-chloropropionate esters and a wide range of amines when the reaction is catalysed by Candida cylidracea lipase. The enantioselection of the enzyme in this aminolysis reaction depends on the substrate and nucleophile structure and reaction conditions. This lipase can catalyze a transamidation reaction if N-trifluoroethyl-2-chloropropionamide is used as substrate. In this way, amides are obtained in high-moderate enantiomeric excesses. The aminolysis of ethyl (±)-2-methylbutyrate with aliphatic amines is achieved using CC and PS lipases as catalysts.

CANDIDA ANTARCTICA LIPASE CATALYZED RESOLUTION OF ETHYL ()-3-AMINOBUTYRATE

Abstract Candida antarctica lipase efficiently catalyzes acetylation and hydrolysis of ethyl (±)-3-aminobutyrate.

CAL-B-catalyzed resolution of some pharmacologically interesting β-substituted isopropylamines

Abstract Some pharmacologically active amines such as amphetamine, the isomeric o-, m- and p-methoxyamphetamines, 4-phenylbutan-2-amine and mexiletine, as well as their corresponding acetamides, have been prepared in high yields and with very high enantiomeric excesses. The method consists of the Candida antarctica lipase B (CAL-B)-mediated enantioselective acetylation of racemic amines using ethyl acetate as solvent and acyl donor. The enzyme follows Kazlauskas’ rule with all amines, (R)-amides being obtained as the major enantiomer in all cases. From the conversion values measured for both enantiomers, it can be deduced that the size of the substituents attached to the stereocenter is responsible for the enantioselectivity and rate of some of these reactions.

Regioselective enzymatic acylation of complex natural products: expanding molecular diversity

Enzymatic catalysis has become a common tool in both academia and industrial chemistry. The efforts of chemists over recent decades have led to the rationalization of the mechanism of action of biocatalysts, which have been routinely incorporated into many synthetic sequences. Nowadays, a further step consists in expanding the application of enzymes to the modification of complex molecular scaffolds common to many pharmaceutical leads isolated from nature. Regioselective enzymatic acylation is a process which has been profitably applied for this purpose in recent times, leading to new drugs with improved activity, stability and pharmacokinetic properties. This tutorial review provides an overview of this subject employing two classes of enzymes, hydrolases and acyltransferases, in the recently concluded decade although some representative older studies are commented upon, if required. We shall place special emphasis on those examples in which the novel acylated derivatives have improved the activity or properties of the parental molecules.

Optically active dioxatetraazamacrocycles: chemoenzymatic syntheses and applications in chiral anion recognition

Two new C2 and D2 symmetrical dioxatetraaza 18-membered macrocycles [(R,R)-1 and (S,S,S,S)-2] are efficiently synthesized in enantiomerically pure forms by a chemoenzymatic method starting from (+/-)-trans-cyclohexane-1,2-diamine. The protonation constants and the binding constants with different chiral dicarboxylates are determined in aqueous solution by means of pH-metric titrations. The triprotonated form of (S,S,S,S)-2 shows moderate enantioselectivity with malate and tartrate anions (deltadeltaG=0.62 and 0.66 kcal mol(-1), respectively), being the strongest binding observed in both cases with the L enantiomer. Good enantiomeric discrimination is obtained with tetraprotonated (R,R)-1 and N-acetyl aspartate, the complex with the D-enantiomer being 0.92 kcalmol(-1) more stable than its diastereomeric counterpart. Despite the lack of enantioselectivity of tri- and tetraprotonated (R,R)-1 for the tartrate anion, a very good diastereopreference for meso-tartrate is found. All these experimental results allow us to propose a model for the host-guest structure based on coulombic interactions and hydrogen bonds.

Candida antarctica B lipase catalysed resolution of (±)-1-(heteroaryl)ethylamines

Abstract Candida antarctica B lipase is an efficient catalyst for the enantioselective acetylation of (±)-1-(heteroaryl)ethylamines (±)- 1a-c .

Lipase-catalyzed synthesis of optically active amides in organic media

Abstract Lipases from Candida cylindracea and Candida antarctica catalyze the aminolysis of activated and nonactivated esters respectively. The degree of enantioselectivity depends on the amine.

Sequential biocatalytic resolution of (±)-trans-cyclohexane-1,2-diamine. Chemoenzymatic synthesis of an optically active polyamine

Candida antarctica lipase-catalysed double monoaminolysis of dimethyl malonate by (±)-trans-cyclohexane-1,2-diamine allows the sequential resolution of the latter compound, affording an enantiopure bis(amidoester), (R,R)-3, which is subsequently transformed into an optically active polyamine, (R,R)-9.

Practical enzymatic route to optically active 3-hydroxyamides. Synthesis of 1,3-aminoalcohols

Abstract Candida antarctica lipase (CAL) is a very efficient catalyst for the enantioselective aminolysis of different racemic 3-hydroxyesters with aliphatic amines. The degree of enantioselectivity exhibited by the lipase depends on the substrate and nucleophile, but in the most cases, the E values obtained are very satisfactory. CAL also catalyzes the aminolysis of ethyl (±)-3,4-epoxybutyrate and the epoxyamide was achieved with high e.e. The chemical reduction of the 3-hydroxyamides obtained by enzymatic aminolysis yields the corresponding 1,3-aminoalcohols.

Lipase-catalyzed aminolysis and ammonolysis of β-ketoesters. Synthesis of optically active β-ketoamides.

Abstract Aminolysis and ammonolysis reactions of β-ketoesters catalysed by Candida antarctica lipase are very efficient methods for the preparation of β—ketoamides. When racemic amines are used in these processes, the corresponding optically active β—ketoamides are obtained with moderate-high enantiomeric excesses.