Efficient access to enantiomerically pure cyclic α-amino esters through a lipase-catalyzed kinetic resolution

Abstract

A series of α-amino acid derivatives containing the 2,3-dihydroindole or octahydroindole core have been chemoenzymatically synthesized in good overall yields and high enantiomeric purity under mild reaction conditions using lipases for the introduction of chirality. Candida antarctica lipase type A has shown excellent activity and high enantiodiscrimination ability towards the two cyclic amino esters used as substrates. The selectivity of the process proved to be greatly dependent on the alkoxycarbonylating agent. Thus, the enzymatic kinetic resolution of methyl indoline-2-carboxylate has been successfully achieved using 3-methoxyphenyl allyl carbonate, whereas (2R,3aR,7aR)-benzyl octahydroindole-2-carboxylate required the less reactive diallyl carbonate.

Hydrolases in the Stereoselective Synthesis of N-Heterocyclic Amines and Amino Acid Derivatives

“…84 The appropriate choice of the alkoxycarbonylating agent allowed the isolation in enantiopure form of (S)-methyl-(N-allyloxycarbonyl)indoline-2-carboxylate 94 when using 3-methoxyphenyl allyl carbonate or (2S,3aS,7aS)-benzyl(N-allyloxycarbonyl)octahydroindole-2-carboxylate (96) with diallyl carbonate (Scheme 35). Very recently, our research group has tested the enzymatic alkoxycarbonylation of methyl-3-indoline carboxylate (97) using CAL-B as biocatalyst.…”

Access to the cis‐Fused Stereoisomers of Proline Analogues Containing an Octahydroindole Core

“…[34] In particular, (R)-and (S)-indoline-2-carboxylic acids have been prepared by chemical resolution with diverse crystallizing agents, [19a,19c,20a,35] chemical synthesis through catalytic asymmetric hydrogenation of indoles, [36] intramolecular aryl aminations, [37] asymmetric deprotonation of N-Boc-indoline followed by carbonylation, [38] and by enzymatic methods. [39] Moreover, both (R)-and (S)-28 have become commercially available.…”

Gene cloning and molecular characterization of the Talaromyces thermophilus lipase Catalyzed efficient hydrolysis and synthesis of esters

“…Apart from their hydrolysis properties in aqueous medium, lipases in nonaqueous medium are efficient catalysts in the kinetic resolution of chiral compounds, synthesis of esters and peptides, and preparation of biodiesel by trans-esterification (Alatorre-Santamarίa et al, 2009;Yang et al, 2009). Lipases are also extensively used in detergents formulations and food processing (Pandey et al, 1999) as well as in biological degradation of fatty waste (Hansan et al, 2006).…”