Neuere Entwicklungen in der katalytischen asymmetrischen Synthese von α‐ und β‐Aminosäuren

Abstract

Zur stereoselektiven Synthese von Aminosäuren, die von zentraler Bedeutung für den Aufbau chiraler Naturstoffe und Pharmazeutika ist, wird neben Enzymen ein breites Sortiment von chiralen Reagentien, Auxiliaren und Katalysatoren eingesetzt. Effiziente Methoden zur Synthese von chiralen proteinogenen und nichtproteinogenen Aminosäuren beruhen häufig auf asymmetrischen Reaktionen unter Verwendung katalytischer Mengen chiraler Verbindungen. Dieser Kurzaufsatz fasst neuere Entwicklungen zur katalytischen Synthese von α‐ und β‐Aminosäuren zusammen.

Highly Enantioselective Decarboxylative Mannich Reaction of Malonic Acid Half Oxyesters with Cyclic Trifluoromethyl Ketimines: Synthesis of β‐Amino Esters and Anti‐HIV Drug DPC 083

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Optically active b-amino esters are an important class of molecules in biological systems and organic synthesis. [1] Direct asymmetric Mannich reaction [2] of simple esters with imines provides an ideal approach toward the construction of these useful building-blocks. However, such transformation remains a great challenge due to the high pK a value of the a-proton in carboxylic acid derivatives.

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Kinetic Resolution of Aliphatic β‐Amino Acid Amides by β‐Aminopeptidases

“…Promising enzymatic approaches that provide access to enantiopure aromatic b 3 -amino acids include the kinetic resolution of N-terminally modified b 3 -amino acids by porcine kidney acylase [4] and by penicillin G amidase. [5] Furthermore, b 3 -and b 2,3 -amino acid esters of high enantiopurity were prepared in organic solvents with the lipases CAL-A and CAL-B from Candida antarctica.…”

“…[1] Besides well-established chemical methods for the synthesis of enantiopure b-amino acids, [2] enzyme-catalyzed resolutions are an interesting alternative. Unlike kinetic resolution approaches to chiral a-amino acids, [3] the biocatalytic synthesis of enantiopure b-amino acids is generally limited by the availability of suitable enzymes that are able to catalyze reactions with b-amino acid containing compounds.…”

Kinetic Resolution of Oxazinones: An Organocatalytic Approach to Enantiomerically Pure β‐Amino Acids

“…[1][2][3][4] Owing to their unique pharmacological properties in the free form, [5] as cyclized b-lactams, [6] and as structural elements of naturally occurring compounds such as taxol [7] and the dolastatins, [8] there is a high demand in both academia and industry for enantiopure b-amino acids. [9] Besides chiral-auxiliary-based strategies [4] and catalytic asymmetric synthesis [1,[10][11][12][13] the kinetic resolution of racemates is a well-established method for obtaining b-amino acids with high enantiomeric purity. The latter methodology is divided into "classical" chemical resolution processes, in which chiral resolving agents are used in stoichiometric amounts, [14] and enzymatic resolutions, which require acylases, amidases, or lipases.…”