Resolution lactams, enzymatic

In a similar manner, enantiopure l-f-Boc-3-TIPSO-4-CF3-P-lactam 14 was synthesized from benzyloxyacetyl chloride/triethylamine and (V-PMP-CF3-aldimine through [2+2] ketene-imine cycloaddition, enzymatic optical resolution (PS Amano lipase at... 

A classic example of a typical enzymatic resolution on an industrial scale is the acylase-mediated production of L-methionine. This method has also been applied for the production of L-phenylalanine and L-valine. In addition to acylases, amidases, hydantoinases, and /i-lactam hydrolases represent versatile biocatalysts for the production of optically active L-amino acids. A schematic overview of the different type of enzymatic resolutions for the synthesis of L-amino acids is given in Fig. 2. 

In summary, a broad range of large-scale applicable biocatalytic methodologies have been developed for the production of L-amino acids in technical quantities. Among these industrially feasible routes, enzymatic resolutions play an important role. In particular, L-aminoacylases, L-amidases, L-hydantoinases in combination with L-carbamoylases, and /l-lactam hydrolases are efficient and technically suitable biocatalysts. In addition, attractive manufacturing processes for L-amino acids by means of asymmetric (bio-)catalytic routes has been realized. Successful examples are reductive amination, transamination, and addition of ammonia to rx,/fun-saturated carbonyl compounds, respectively. 

Enzymatic hydrolytic resolution of racemic cis /3-lactams provided an alternative to the use of chiral auxiliaries for the synthesis of enantiomerically pure /3-lactam side chain. Sih and his collaborators found that P-30 specifically hydrolyzed the undesired 3-acetate group of the /3-lactam, affording the acetate of the desired enantiomer in 99.5% enantiomeric excess and 47% yield. Manipulations using known chemistry proceeded smoothly to give optically active taxol side chain (245). 

Scheme 2.19 Enzymatic resolution of bicyclic P- and y-lactams via the lactamase method...

Chemoenzymatic methods were recently appHed for the synthesis of a-alkyhdene-y-lactams by Felluga et al. (Scheme 4.53) [85]. Kinetic enzymatic resolution... 

A number of research groups have been interested in die synthesis of aminodiol 22. This compound is believed to mimic the transition state for the renin-catalyzed hydrolysis of the peptide angiotensinogen and therefore can be useful as a potential antihypertensive drug. The enzymatic resolution of the 3-acetoxy-P-lactam 23 (Fig. 6) by lipase PS-30 has been demonstrated by Spero et al. [37]. A new approach to the BOC-protected aminodiol 24 via opening of 3,4-cis-disubstituted j3-lactam has been demonstrated. 

For the synthesis of p-lactam antibiotics, the presence of asymmetrical carbon at the 3 and 4 positions is critical to prepare optically active -lactams [197]. Nagai et al. [198] developed enzymatic synthesis of optically active p-lactams by lipase-catalyzed kinetic resolution using the enantioselective hydrolysis of iV-acyloxymethyl p-lactams 108 in an organic solvent (isopropyl ether saturated with water) and the transesterification of N-hydroxymethyl P-lactam 109 in organic solvent (metiiylene chloride) in tiie presence of vinyl acetate as acyl donor (Fig. 37). The reaction yield of 35-50% and e.e. s of 93 to more than 99% were obtained depending on the specific substrate used in the reaction mixture, Lipase B from Pseudomonas fragi and lipase PS-30 from Pseudomonas sp. were used in the reaction mixture. 

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