Conversion of γ‐ and δ‐Keto Esters into Optically Active Lactams. Transaminases in Cascade Processes

Abstract

A one-pot two-step enzymatic strategy has been designed for the production of optically active gand d-lactams in aqueous medium under mild conditions. The approach is based on the biotransamination of ethyl or methyl keto esters bearing different alkyl or aryl substitution patterns at a-position to the ketone functionality. In this manner, the keto esters were transformed into the corresponding amino esters with excellent conversions, which underwent spontaneous cyclisation in the reaction medium without addition of external reagents. Depending on the transaminase selectivity, both lactam enantiomers can be obtained, so initial enzyme screenings were performed using commercially available and made in house enzymes. Reaction conditions were optimised focusing on the substrate concentration, temperature and ratio of amine donor vs acceptor. Thus, ten g-and d-lactams were obtained in good to high isolated yields (70-90%) and excellent selectivities (94-99%) after one or two days at 30 or 45 8C.

Glutamate as an Efficient Amine Donor for the Synthesis of Chiral β‐ and γ‐Amino Acids Using Transaminase

“…In the case of β‐amino acids, additional enzyme i. e. lipase needs to be added for the hydrolysis of ester substrates . As, ATAs used in this study do not show reactivity towards β‐keto esters, β‐keto acids were used as substrates for the synthesis of corresponding β‐amino acids.…”

The Impact of Recent Developments in Technologies which Enable the Increased Use of Biocatalysts

“…Gotor‐Fernández et al reported a related transamination, using γ ‐ and δ ‐keto esters. The ketone is reduced by a transaminase (Scheme ) and the cyclization of the resulting amino esters result in γ ‐ and δ ‐ lactams . The use of amino alcohols has been recently reported in the synthesis of β ‐, γ ‐ or δ ‐lactams, in a bienzymatic cascade …”

“…the cyclization of the resulting amino esters result in γand δlactams. [14] The use of amino alcohols has been recently reported in the synthesis of -, γor δ-lactams, in a bienzymatic cascade. [15] Scheme 9.…”

Stereoselective Synthesis of 1‐Arylpropan‐2‐amines from Allylbenzenes through a Wacker‐Tsuji Oxidation‐Biotransamination Sequential Process

“…The use of organic cosolvents improves the substrate solubilisation in ATA-catalysed transformations, favouring higher reaction conversion values as the enzyme activity is usually completely maintained at low volumes of organic solvent (typically DMSO, DMF or MeCN) [33] and, besides, showed a beneficial effect on the Wacker-Tsuji step. For this reason, MeCN (2.5-10% v/v) was selected for further optimisation of the biotransamination experiments over ketone 2 a (Table 4).…”