Preparation of chiral prim-, and sec-amines employing biocatalysts

Preparation of chiral prim-, and sec-amines employing biocatalysts

Kroutil, Wolfgang; Simon, Robert C.; Busto, Eduardo; Richter, Nina; Tauber, Katharina; Fuchs, Christine S.; Pressnitz, Desiree; Fischereder, Eva-Maria; Lechner, Horst; Zepeck, Ferdinand

Abstract:

Optically pure α-chiral primary amines can be prepared by reductive amination employing metal-, ogano- or biocatalysis. Using biocatalysts such a ψ-transaminases , α-chiral primary amines were prepared with e.e. up to 99% at a substrate concentration of 50 mM (Scheme 1). The formal asymmetric reductive amination of ketones was achieved giving access to the (S)-as well as the (R)-enantiomer. By this methodology various building blocks for bioactive compounds were prepared in aqueous buffer. Using appropriate conditions it was shown that the amination can also be performed in organic solvents, thereby simplifying workup of the amine compared to reactions in aqueous phase. Furthermore, it was demonstrated, that the biocatalyst can perfectly differentiate between different keto groups within a single molecule; for instance, when transforming 1,5-diketones only the keto moiety in (ψ-1)-position was aminated avoiding thereby sophisticated protection strategies. The obtained mono-aminated intermediate underwent spontaneous cyclization giving access to secondary amines after chemical diastereoselective reduction. The amination of primary alcohols represents a challenging task for chemistry. Nature has not foreseen this reaction to be performed by a single enzyme in one step. Consequently, we designed an artificial biocatalytic pathway transforming prim- alcohol to the corresponding amine via oxidation followed by reductive amination. The pathway was set up in that way that the hydride abstracted in the oxidation step is reused in the reductive amination. By employing such an enzyme cascade alcohols were successfully as demonstrated for the preparation of 1, ψ-alkyldiamines as building blocks for polymers (Figure 1).

Optically pure α-chiral primary amines can be prepared by reductive amination employing metal-, ogano- or biocatalysis. Using biocatalysts such a ψ-transaminases , α-chiral primary amines were prepared with e.e. up to 99% at a substrate concentration of 50 mM (Scheme 1). The formal asymmetric reductive amination of ketones was achieved giving access to the (S)-as well as the (R)-enantiomer. By this methodology various building blocks for bioactive compounds were prepared in aqueous buffer. Using appropriate conditions it was shown that the amination can also be performed in organic solvents, thereby simplifying workup of the amine compared to reactions in aqueous phase. Furthermore, it was demonstrated, that the biocatalyst can perfectly differentiate between different keto groups within a single molecule; for instance, when transforming 1,5-diketones only the keto moiety in (ψ-1)-position was aminated avoiding thereby sophisticated protection strategies. The obtained mono-aminated intermediate underwent spontaneous cyclization giving access to secondary amines after chemical diastereoselective reduction. The amination of primary alcohols represents a challenging task for chemistry. Nature has not foreseen this reaction to be performed by a single enzyme in one step. Consequently, we designed an artificial biocatalytic pathway transforming prim- alcohol to the corresponding amine via oxidation followed by reductive amination. The pathway was set up in that way that the hydride abstracted in the oxidation step is reused in the reductive amination. By employing such an enzyme cascade alcohols were successfully as demonstrated for the preparation of 1, ψ-alkyldiamines as building blocks for polymers (Figure 1).

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DOI: 10.5151/chempro-15bmos-4-final-abstract-Kroutil

Referências bibliográficas

• [1] 1 Koszelewski, D.; Tauber, K.; Faber, K.; Kroutil, W. Trends Biotechnol. 2010, 28, 324-332.
• [2] 2 Kroutil, W.; Fischereder, E.-M.; Fuchs, C. S.; Lechner, H.; Mutti, F. G.; Pressnitz, D.; Rajagopalan, A.; Sattler, J. H.; Simon, R. C.; Siirola, E. Org. Process Res. Dev. 2013, 17, 751-759.
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• [5] 5 Simon, R. C.; Grischek, B.; Zepeck, F.; Steinreiber, A.; Belaj, F.; Kroutil, W. Angew. Chem. Int. Ed. 2012, 51, 6713-6716.
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• [7] 7 Sattler, J. H.; Fuchs, M.; Tauber, K.; Mutti, F. G.; Faber, K.; Pfeffer, J.; Haas, T.; Kroutil, W. Angew. Chem. Int. Ed. 2012, 51, 9156-9159.

Como citar:

Kroutil, Wolfgang; Simon, Robert C.; Busto, Eduardo; Richter, Nina; Tauber, Katharina; Fuchs, Christine S.; Pressnitz, Desiree; Fischereder, Eva-Maria; Lechner, Horst; Zepeck, Ferdinand; "Preparation of chiral prim-, and sec-amines employing biocatalysts", p-319-319. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 2, Dezembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-15bmos-4-final-abstract-Kroutil