Carbonyl Amination Followed by Spontaneous Ring Closure

Carbonyl Amination Followed by Spontaneous Ring Closure 

An extension of this method was described recently (using 1,5-diketone with R= CgHjg) in order to access also both enantiomers of the alkaloid isosolenopsin, a secreted fire venom alkaloid with multiple biological activities. Despite the 

Just by the choice and the order of the m-TAs employed, deracemization can be used to access the (R)- as well as the (S)-enantiomer with enantiomeric excess of up to 99% at excellent conversions of up to 99% (Table 4.4). While in first studies stoichiometric amounts of pyruvate were added in the KR, in the optimized 

Cascade Reactions ofco-TAs with Lyases and C-C Hydroiases/Lipases 

In order to establish the two-step strategy, both en2ymatic steps were evaluated separately this included the engineering of the TK to accept the non-natural substrate propanal, and use of a bioinformatic-based strategy to identify a suitable co-TA with the ability to accept the ligation product. The final reaction was performed in two sequential steps, because preliminary experiments indicated that the co-TA also aminates the TK substrates in the presence of an amine donor. Notably, for the reductive amination (second step), cheap and achiral 2-PrNH2 could be used successfully as an alternative amine source. The final product was isolated after the two enzymatic steps, with a calculated overall isolated yield of 18% under nonoptimized conditions. However, while the TK-catalyzed C-C bond formation already displayed suitable conversions (23%), the cb-TA was identified to be the bottleneck of the cascade reaction further optimization, especially with respect to the reductive amination, should facilitate a more efficient process. 

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