An efficient single-enzymatic cascade for asymmetric synthesis of chiral amines catalyzed by ω-transaminase

Abstract

An efficient single-enzymatic cascade approach for the asymmetric synthesis of chiral amines has been developed, which applies the amino donor 3-aminocyclohexa-1,5-dienecarboxylic acid spontaneously tautomerizing to reach reaction completion with excellent ee values.

But‐2‐ene‐1,4‐diamine and But‐2‐ene‐1,4‐diol as Donors for Thermodynamically Favored Transaminase‐ and Alcohol Dehydrogenase‐Catalyzed Processes

“…[d] Amine donor described by Berglund and co-workers (see Scheme 1b). [10] [e] Amine donor described by Turner and co-workers (see Scheme 1b). [11] Likewise, diol cis-1, previously tried as synthetic precursor of diamine cis-2, was envisioned as suitable cosubstrate for ADH-mediated bioreductions in a similar way as shown by Hollmann and co-workers with the saturated derivatives.…”

“…Finally, we have compared the conventional methodology using an excess of isopropylamine, with thermodynamically favored strategies employed for TA-catalyzed reactions, calculating the theoretical value of waste generated according to the reaction equation. [19] To perform this, we have used the EATOS program, [20] assuming a cosubstrate molar excess as described by the corresponding authors, [10,11] and a quantitative conversion of a model ketone (6a, Table 2). As can be seen, our methodology (entry 4) was perfectly comparable to similar previously described strategies (entries 2 and 3), while greatly improving the standard conditions using isopropylamine (entry 1).…”

“…Based on previously described protocols that make use of designed cosubstrates to favor TA-mediated processes, [10,11] we envisaged that simple 1,4-diamines could be used for this purpose. Once the ω-aminoaldehyde intermediates were formed, they could intramolecularly cyclize, thus providing the driving force that could transform quantitatively the carbonylic compound of interest.…”

“…This is due to the thermodynamically favored ring closure of the ω-hydroxyaldehyde intermediate, thus forming the corresponding hemiacetal, which in a subsequent oxidative step renders the final lactone co-product (Scheme 1a). On the other hand, a cyclic amine [10] or a diamine [11] have been described as amine donors that can highly displace the equilibria in TA-catalyzed protocols due to ring aromatization (Scheme 1b). However, the high cost of these tailored amines and difficulties on separating the excess of the donors from the products make interesting the study of other alternatives.…”

Transaminases and their Applications

“…A novel single enzyme reaction with an ω-transaminase from Chromobacterium violaceum and 3-aminocyclohexa-1,5-dienecarboxylic acid as the amino donor was examined [65]. As shown in Scheme 29.5, a prochiral ketone (a) and the chosen amino donor (b) were leading to chiral amines.…”