Synthesis of chiral α-hydroxy amides by two sequential enzymatic catalyzed reactions

Abstract

Enantiomerically pure alpha-hydroxy amides have been prepared from the corresponding alpha-oxo esters by the use of a double sequence reaction involving in a first step the highly enantioselective Saccharomyces cerevisiae bioreduction and then in a second step, the resulting alpha-hydroxy esters followed a non-enantiospecific lipase catalyzed aminolysis with n-butylamine reaction. In the first non-organic solvent process, the moistened baker's yeast reduced seven alpha-oxo esters with high conversions degree (93% for one substrate and >99% for the others) and high enantioselectivities [>99% for all the substrates except for ketopantoyl lactone, which gave 88% of enantiomeric excess (ee)]. At the same way, the isolated resulting chiral alpha-hydroxy esters were subjected to the second Candida antarctica lipase fraction B (CAL-B) catalyzed aminolysis in dioxane conducting to the corresponding chiral alpha-hydroxy amides with high conversions degree, between 88 and 99%. Both processes were carried out at 28-30 degrees C.

Biocatalytic Construction of Quaternary Centers by Aldol Addition of 3,3-Disubstituted 2-Oxoacid Derivatives to Aldehydes

“…Otherwise, an additional extraction with aqueous buffer at neutral pH removed the remaining starting 2-oxoacid 1 , which was the main impurity present. The 2-oxo group can be reduced, affording α-hydroxy-γ-butyrolactones (e.g., ( R )- or ( S )-pantolactone and analogues), chiral auxiliaries, and important precursors for the synthesis of naturally occurring and synthetic biologically active compounds . Elaborated chemical transformations on the carboxylate group such as oxidative decarboxylation followed by esterification lead to different 3-hydroxyesters ( 5a – i and amide 5j , Scheme B) with application as building blocks in the synthesis of pharmaceutical compounds and polymers, coating oligomers, and dendrimers, e.g., 2,2-bis­(hydroxymethyl) propionic acid derivative 5g …”

Yeast‐Mediated Stereoselective Synthesis

“…baker's yeast gave the corresponding α-hydroxy esters. The esters were transformed by a nonenantiospecific lipase-catalyzed aminolysis to yield butylamides [241]. Numerous examples have been reported for the reduction of acyclic β-keto esters, and their results were explained by applying Prelog's rule [95,97,[242][243][244][245][246].…”

Enzymatic Reduction of 9-Methoxytariacuripyrone by Saccharomyces cerevisiae and Its Antimycobacterial Activity

“…It is well known that BY contains enzymes that carry out several chemical reactions, such as: asymmetrical reduction of the carbonyl group to an alcohol group with high yields; carbonyl compounds with several substituents (Me, Et, n -Pr, n -Bu, Bz) are also reduced [ 4 ], and some aldehydes, oxo esters, and α-oxo esters are also reduced by BY [ 7 ]. Thus, BY is widely utilized as a bio-reagent in chemical synthesis [ 8 ].…”