Chemoenzymatic approaches

Stereoinversion Stereoinversion can be achieved either using a chemoenzymatic approach or a purely biocatalytic method. As an example of the former case, deracemization of secondary alcohols via enzymatic hydrolysis of their acetates may be mentioned. Thus, after the first step, kinetic resolution of a racemate, the enantiomeric alcohol resulting from hydrolysis of the fast reacting enantiomer of the substrate is chemically transformed into an activated ester, for example, by mesylation. The mixture of both esters is then subjected to basic hydrolysis. Each hydrolysis proceeds with different stereochemistry - the acetate is hydrolyzed with retention of configuration due to the attack of the hydroxy anion on the carbonyl carbon, and the mesylate - with inversion as a result of the attack of the hydroxy anion on the stereogenic carbon atom. As a result, a single enantiomer of the secondary alcohol is obtained (Scheme 5.12) [8, 50a]. 

Purkarthofer, T., Pabst, T., van den Broek, C. et al. (2006) Large-scale synthesis of (/ )-2-amino-l-(2-furyl) ethanol via a chemoenzymatic approach. Organic Process Research Development, 10, 618-621. 

Several approaches to statin side-chain intermediates have so far been discussed. Whereas these chemoenzymatic approaches provide clear benefits over the chemical processes, they do not harness the tme potential of biocatalysis as the biotransformations have simply been inserted into the existing chemical route. Wong and co-workers have developed a more biosynthetic-hke approach by using a mutant 2-deoxyiibose-5-phosphate aldolase (DERA)... 

Cabrele et have used a chemoenzymatic approach in the preparation of the four different optically pure forms of 3-carboxycyclopentylglycine. Chemical synthesis delivered a mixture of epimeric cyclopentylgly-... 

P-Adrenergic-blocking agents, such as propranolol, have been synthesized by different chemoenzymatic methods where the key step to introduce the chirality is an enzymatic acylation or a hydrolysis process. The main reason to prepare these amino alcohols in optically pure form is due to the fact that the activity of these pharmaceuticals resides in the (S)-enantiomer. In Scheme 10.1 we have represented a chemoenzymatic approach that has been carried out for the preparation of this dmg where the key step is the resolution of the key intermediate 1-chloro-... 

Hydrolases in Polymer Chemistry Chemoenzymatic Approaches to Polymeric Materials... 

Various a-methylenemacrolides were enzymatically polymerized to polyesters having polymerizable methacrylic methylene groups in the main chain (Fig. 3, left). The free-radical polymerization of these materials produced crosslinked polymer gels [10, 12]. A different chemoenzymatic approach to crosslinked polymers was recently introduced by van der Meulen et al. for novel biomedical materials [11]. Unsaturated macrolactones like globalide and ambrettolide were polymerized by enzymatic ROP. The clear advantage of the enzymatic process is that polymerizations of macrolactones occur very fast as compared to the chemically catalyzed reactions [13]. Thermal crosslinking of the unsaturated polymers in the melt yielded insoluble and fully amorphous materials (Fig. 3, right). 

Kokas OJ, Banwell MG, Willis AC (2008) Chemoenzymatic Approaches to the Montanine Alkaloids A Total Synthesis of (+)-Nangustine. Tetrahedron 64 6444... 

Since neither the chemical nor the enzymatic synthesis alone can assist in the rational design of a new generation of therapeutic carbohydrate target structures, the chemoenzymatic approaches have been successfully utilized [40-42]. 

Carbohydrate postglycosylation modifications, including methylations, acylations, and attachment of complex chromophores, are also used for glycodiversification of NPs in chemoenzymatic approaches. 

Bonini, C. Chiummiento, L. Funicello, M. Marconi, L. Righi, G. Chiral polypropionate subunit by a chemoenzymatic approach. Tetrahedron Asymmetry 1998, 9, 2559-2561. 

Another impetus is to use the chemoenzymatic approach to synthesize structurally defined oligosaccharides. Early attempts targeted a single product from a specialized... 

TABLE 9.1 Summary of HS/Heparin Oligosaccharides Prepared by the Chemoenzymatic Approach... 

Chemoenzymatic approach served as an alternative method for the synthesis of complex carbohydrate-containing molecules. The use of biosynthetic enzymes not only provides high regioselectivity and stereoselectivity for the formation of glycosidic bonds but also solves the problems of protection and deprotection steps required by chemical synthesis. The discovery of bacterial counterparts and the advance in bioengineering technology led to breakthroughs in complex carbohydrate synthesis. 

In this chapter we summarize our synthesis of positionally labeled symmetrically structured TAGs of the MLM-type constituting pure homogeneous MCFA and EPA or DHA by a chemoenzymatic approach. The synthesis of similarly structured enantiopure ELs of the l-O-alkyl-xn-glycerol type will also be briefly discussed. The main emphasis will be put on describing the synthesis of asymmetrically structured MLM type TAGs. 

The two-step chemoenzymatic approach starting from glycerol to synthesize the symmetric MLM-type structured TAGs is illustrated in the scheme in Figure 24.2. In the first step lipase regioselectivity was exploited to synthesize symmetric 1,3-diacylglycerols (DAGs) of the MCFA. This was followed by chemical introduction of the PUFA into the mid-position. 

Figure 24.2. Synthesis of positionally labeled, symmetrically structured TAGs of the MLM-type constituting MCFA at the end-positions, and EPA or DHA at the midposition, by a chemoenzymatic approach based on immobilized Candida antarctica lipase (CAL).

Figure 24.4. Synthesis of enantiomerically pure, positionally labeled, structured ether lipids of the ALM type by chemoenzymatic approach, starting from enantiomerically pure chimyl (S-4), batyl (S-5) and selachyl (S-6) alcohols.

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