Chemoenzymatic synthesis strategy

Scheme 4.10 General strategy for the chemoenzymatic synthesis of iminocyclitols based in the use of aldolases and palladium-mediated reductive amination.

The second strategy for the chemoenzymatic synthesis of block copolymers from enzymatic macroinitiators employs an individual modification step of the enzymatic block with an initiator for the chemical polymerization (route B in Fig. 4). This strategy has the advantage that it does not depend on a high incorporation rate of the dual initiator. On the other hand, quantitative end-functionalization becomes more... 

Figure 2 One-pot three-enzyme chemoenzymatic synthesis of sialosides containing sialic acid modifications. In this strategy, mannose or ManNAc derivatives are chemically or enzymatically synthesized. These compounds are then used by a recombinant coli K-12 sialic acid aldolase to obtain sialic acids and their derivatives followed by an N. meningitidis CMP-sialic acid synthetase for the formation of CMP-sialic acids. From which, sialic acids can be transferred to lactose, LacNAc, galactose, GalNAc, or their derivatives by a multifunctional P. muitocida sialyltransferase (PmSTl) or a P, damseia a2,6-sialyltransferase (Pd2,6ST) to form a2,3- or a2,6-linked sialosides in one pot without the isolation of intermediates.

The second strategy for the chemoenzymatic synthesis of block copolymers from enzymatic macroinitiators employs an individual modification step of the... 

Interaction between the glycoprotein E-selectin (expressed on the surface of endothelial cells) and the sialyl Lewis 1 ligand structures on the surface of neutrophils is a major event in inflammation, infection, and metastasis. Both chemical and enzymatic syntheses have been described for the synthesis of the sialyl Lewisx structure. A summary of the general strategy used in chemoenzymatic synthesis is shown here. Extensive in situ regenerations of the sugar nucleotides are not shown in the scheme.97... 

Fig. 10) [165], The Cytel corporation in San Diego has been able to scale-up this process for the routine production of kilogram quantities in each run of reactions [144]. The sialyl Le tetrasaccharide and its analogs are of pharmaceutical interest in the context of new treatments for chronic inflammatory diseases (psoriasis, rheumatoid arthritis), tumors, and tissue injuries following a heart attack, stroke, or organ transplant. Sialyl Lex and its analogs are therefore enthusiastically pursued by several pharmaceutical companies. Strategies for the solid-phase chemoenzymatic synthesis of glycopeptides (and glycolipids) containing sialyl Lex have also been designed and reported [144,156, and references therein].

Alkyl-4-oxy-3,4-dihydroisocoumarins are enantioselectively prepared by oxylactonization ofo-(alk-l-enyl)benzoates promoted by the in situ-generated chiral lactate-based hypervalent iodine(III) catalysts (13EJ07128). Chemoenzymatic synthesis of 3,4-dialkyl-3,4-dihydroisocoumarins involves one-pot dynamic kinetic reductive resolution processes catalyzed by E. co/i/alcohol desidrogenase. This strategy consists in the bioreduction of various racemic ketones to the corresponding enantiopure alcohols followed by intramolecular acidic cyclization (Scheme 71) (130L3872). 

A related approach was also described for the chemoenzymatic synthesis of 4-phenylpyrrolidin-2-one, a cyclic analog of the pharmaceutically relevant y-aminobutyric acid (GABA). The strategy involved a m-TA-catalyzed dynamic KR, followed by an intramolecular lactamization cascade (Scheme 4.12) [45]. 

A strategy of chemoenzymatic synthesis of C8-modified sialic acid analogues was recently reported by Withers and co-workers (Scheme 3) [83], The C8-modified sialic acid precursors 8-11 were synthesized from compounds 5-7, and each was converted to its CMP donor using a bacterial CMP-sialic acid synthetase. The Cst-1, an a 2,3-sialylatransferase from Campylobacter jejuni, was then selected and successfully used for the synthesis of sialyl thiolactoside 12-15. Notably, Cst-1 was shown to be more desirable for the synthesis of C8-modified sialyl lactose in comparison with another sialyltransferase PM0188h, which exhibited more hydrolysis activity toward natural substrates. 

L. Werner, A. Machara, B. Sullivan, 1. Carrera, M. Moser, D.R. Adams, T. Hudlicky, 1. Andraos, Several generations of chemoenzymatic synthesis of oseltamivir (tamiflu) evolution of strategy, quest for a process-quality synthesis, and evaluation of efficiency metrics, 1. Org. Chem. 76 (2011) 10050-10067. 

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