High substrate loading

Pathway A employed a reductive cyclization [21] to form 3-carboxy-4-alkyl-pyrrolidin-2-one (17), which could then be converted to pregabalin under acidic conditions pathway B employed a hydro lysis/reduction/decarboxylation analogous to the one used in the first-generahon route via intermediate 18 [7], and pathway C involving a heat-mediated decarboxylation to intermediate 19 followed by a hydrolysis/reduchon sequence to yield pregabalin. In pathway A, the hydro-genahon of 13 was performed in predominantly aqueous medium at neutral pH, with catalyhc amounts of Raney nickel, and afforded 17 in >95% isolated yield. The reduction could be performed at relatively high substrate loads (0.5-1.OM),... 

A Comparison of Simple Rheological Parameters and Simulation Data for Zymomonas mobilis Fermentation Broths with High Substrate Loading in a 3-L Bioreactor... 

In this context we might point out that both the rat hepato-cyte and mouse liver systems were bathed In media containing high substrate loads, 28 alanine and 20 ethanol for the hepatocytes and 8 alanine and 20 ethanol for the mouse liver. These high loads might Induce an enhanced differential activity of certain metabolic pathways in the two systems. 

Um BH, Hanley TR. (2008). A comparison of simple rheological parameters and simulation data for Zymomonas mobilis fermentation broths with high substrate loading in a 3-1 hioreactoT. Appl Biochem Biotechnol, 145(1-3), 29-38. 

Table 9.1 Asymmetric reduction of keto esters at high substrate loadings in aqueous media.

It should be mentioned that the efficient reduction processes at extremely high substrate loading in aqueous media are achieved under the precondition of an available reductase with exceptionally high activity and substrate tolerance. Within these extraordinary cases, the hardly water-soluble substrate, in fact, serves as a second phase [5], as the solubility limit is exceeded. One problem associated with the large amount of substrate in aqueous media is the tendency to form emulsions in the workup, requiring tedious product separation and decrease in isolated yields. 

High substrate loading, however, can be also achieved in the absence of an organic solvent even when hydrophobic compounds with low water solubility are used. The resulting emulsions (in case of liquid substrates) or slurry systems (in case of solid substrates) represent suitable reaction media under the prerequisite that mass transfer from the organic phase of the emulsion or slurry into the... 

The use of a recombinant whole-cell catalyst based on an ADH and a GDH also turned out to be a valuable approach for the synthesis of the a-hydroxy ester (R)-35, which serves as a key intermediate for clopidogrel (Scheme 23.17) [98]. To this end, Ema and Sakai et al. designed E. coli cells overexpressing an ADH from S. cerevisiae and a GDH for in situ cofactor recycling. This reduction runs at a high substrate loading of 198 g/1 and leads to (R)-35 with 86% conversion, in 82% yield and with... 

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