Preliminary investigation of the yeast-mediated reduction of β-keto amides derived from cyclic amines as potential resolution methodology

Benefits of Unconventional Methods in the Total Synthesis of Natural Products

“…The reductions were also conducted with ketoamides, as shown in Figure . The level of resolution was found to depend somewhat on the steric bulk of the substituents at the chiral center. , Finally, the reduction protocol was applied to the ketoester 131 containing the azidodiene functionality, as shown in Figure …”

“…The level of resolution was found to depend somewhat on the steric bulk of the substituents at the chiral center. 57,58 Finally, the reduction protocol was applied to the ketoester 131 containing the azidodiene functionality, as shown in Figure 15. 59 Reasonable levels of resolution were attained in the intermediates 132 and 133, which furnished, after separation and hydrolysis, the enantiomerically enriched alcohols 134 and 135.…”

Yeast‐Mediated Stereoselective Synthesis

“…The yields, however, remained low [285] as for many other β-keto esters possessing a substituent in the α-position [155,264,[286][287][288][289][290][291][292]. In addition, several racemic β-keto amides have been reduced [293], and the substrate acceptance and the enantioselectivity of the yeast reductases have been assessed [294]. Similarly, the bioreduction of α-keto β-lactams allowed the synthesis of precursors of novel paclitaxel analogues [295][296][297].…”

Novel (S)-Selective Hydrolase from Arthrobacter sp. K5 for Kinetic Resolution of Cyclic Amines

“…Optically active amines can be prepared from racemic amine by diastereomeric salt formation using chiral carboxylic acids [17] or by stereoselective bioconversion of racemic N-acyl amine using enzymes [18][19][20]. Several studies on chiral cyclic amines' preparation via chemical or enzymatic resolution have been reported (Scheme 1) [21][22][23][24][25][26][27][28][29][30][31][32][33]. In the enzy- Optically active amines can be prepared from racemic amine by diastereomeric salt formation using chiral carboxylic acids [17] or by stereoselective bioconversion of racemic N-acyl amine using enzymes [18][19][20].…”

“…Until now, the existing hydrolases described above have been used to synthesize chiral secondary amines; however, their variation was limited. Other enzymatic processes need cyclic amines with functional groups, such as 2-hydroxymethylpiperidine, to yield products with low enantioselectivity in many cases due to the low chirality-recognition ability of the enzyme [31][32][33]. Interestingly, there is no approach to directly obtain chiral 2-substituted piperidines from racemic N-acyl derivatives by kinetic resolution using a hydrolase.…”