451503-29-0Relevant articles and documents
Identification of (S)-selective transaminases for the asymmetric synthesis of bulky chiral amines
Pavlidis, Ioannis V.,Wei?, Martin S.,Genz, Maika,Spurr, Paul,Hanlon, Steven P.,Wirz, Beat,Iding, Hans,Bornscheuer, Uwe T.
, p. 1076 - 1082 (2016/11/02)
The use of transaminases to access pharmaceutically relevant chiral amines is an attractive alternative to transition-metal-catalysed asymmetric chemical synthesis. However, one major challenge is their limited substrate scope. Here we report the creation of highly active and stereoselective transaminases starting from fold class I. The transaminases were developed by extensive protein engineering followed by optimization of the identified motif. The resulting enzymes exhibited up to 8,900-fold higher activity than the starting scaffold and are highly stereoselective (up to >99.9% enantiomeric excess) in the asymmetric synthesis of a set of chiral amines bearing bulky substituents. These enzymes should therefore be suitable for use in the synthesis of a wide array of potential intermediates for pharmaceuticals. We also show that the motif can be engineered into other protein scaffolds with sequence identities as low as 70%, and as such should have a broad impact in the field of biocatalytic synthesis and enzyme engineering.
Synthesis of diarylmethylamines via palladium-catalyzed regioselective arylation of 1,1,3-triaryl-2-azaallyl anions
Li, Minyan,Yuecel, Baris,Adrio, Javier,Bellomo, Ana,Walsh, Patrick J.
, p. 2383 - 2391 (2014/05/20)
Diarylmethylamines are of great interest due to their prevalence in pharmaceutical chemistry. As a result, new methods for their synthesis are in demand. Herein, we report a versatile protocol for the synthesis of diarylmethylamine derivatives involving palladium-catalyzed arylation of in situ generated 2-azaallyl anion intermediates. The 2-azaallyl anions are generated by reversible deprotonation of readily available aldimine and ketimine precursors. Importantly, the arylated aldimine and ketimine products do not undergo isomerization under the reaction conditions. Scale-up of the arylation and hydrolysis of the resulting products to furnish diarylmethylamines were also successfully performed. This journal is the Partner Organisations 2014.
A room-temperature protocol for the rhodium(I)-catalyzed addition of arylboron compounds to sulfinimines
Bolshan, Yuri,Batey, Robert A.
, p. 1481 - 1484 (2007/10/03)
(Chemical Equation Presented) The addition of organoboronic acids to chiral sulfinimines proceeds under mild conditions at room temperature, using Rh(I) catalysis in the absence of external phosphine ligands. Clean reaction only occurs in the presence of
Diastereoselective and enantioselective Rh(I)-catalyzed additions of arylboronic acids to N-tert-butanesulfinyl and N-diphenylphosphinoyl aldimines
Weix, Daniel J.,Shi, Yili,Ellman, Jonathan A.
, p. 1092 - 1093 (2007/10/03)
Two new Rh(I)-catalyzed methods for the synthesis of chiral α-branched amines via addition of arylboronic acids to N-tert-butanesulfinyl and N-diphenylphosphinoyl imines have been developed. The syntheses are more functional group tolerant than alternativ
Asymmetric synthesis of diarylmethylamines by diastereoselective addition of organometallic reagents to chiral N-tert-butanesulfinimines: Switchover of diastereofacial selectivity
Plobeck, Niklas,Powell, David
, p. 303 - 310 (2007/10/03)
Diastereoselective addition of organometallic reagents to chiral N-tert-butanesulfinimines gave alkylated adducts in high yields and diastereoselectivities. Cleavage of the chiral auxiliary under mildly acidic conditions gave diarylmethylamines in high yi
