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

Abstract

Abstract. cis-and trans-But-2-ene-1,4-diamine have been prepared and efficiently applied as sacrificial cosubstrates in enzymatic transamination reactions. The best results were obtained with the cis-diamine. The thermodynamic equilibrium of the stereoselective transamination process is shifted to the amine formation due to tautomerization of 5H-pyrrole into 1H-pyrrole, achieving high conversions (78-99%) and enantiomeric excess (up to >99%) by using a small excess of the amine donor. Furthermore, when the reaction proceeded, a strong coloration was observed due to polymerization of 1H-pyrrole.A structurally related compound, cis-but-2-ene-1,4-diol, has been utilized as cosubstrate in different alcohol dehydrogenase (ADH)-mediated bioreductions. In this case high conversions (91-99%) were observed due to a lactonization process. Both strategies are convenient from both synthetic and atom economy points of view in the production of valuable optically active products.

Isopropylamine as Amine Donor in Transaminase‐Catalyzed Reactions: Better Acceptance through Reaction and Enzyme Engineering

“…The downside of this strategy is a very often unfavorable reaction equilibrium, which makes strategies for equilibrium shifting necessary. Therefore several equilibrium displacement techniques were established, for instance involving enzymatic cascades in order to remove co‐products,, utilization of ‘smart‐donors’ which are converted into sacrificial co‐substrates after transamination or application of the amine donor in large excess . In fact, IPA is the industrially favored amine donor for asymmetric syntheses since it is cheap, achiral – so the enantioselectivity of the ATA has not to be considered – and the by‐product acetone is supposed to have a drastic lower reactivity in the back reaction .…”

Asymmetric Synthesis of Chiral Halogenated Amines using Amine Transaminases

“…For this purpose, pyruvate decarboxylase, alanine dehydrogenase, or, most commonly, a combination of lactate dehydrogenase and glucose dehydrogenase (LDH/GDH system) are applied to drive the desired transamination reaction to completeness. More recently, aliphatic diamines were reported as effective amine donors …”

“…reported the synthesis of ( S )‐1‐(5‐fluoropyrimidin‐2‐yl)ethylamine. Gomm et al., Green et al., and Martínez‐Monteroet al . subjected 4‐fluorophenylacetone to the asymmetric synthesis of the corresponding amine.…”

A Photo-Enzymatic Cascade to Transform Racemic Alcohols into Enantiomerically Pure Amines

“…On the other hand, the use of alternative amine donors provides a more favorable thermodynamic equilibrium. However, these molecules are either prohibitively expensive [39] or generate a co-product during the transamination that tends to polymerize, thus complicating product isolation and lowering product yield [40,41]. Therefore, it is not surprising that isopropylamine (IPA) has been used as the preferred amine donor, especially on an industrial scale.…”