L Scale

The immobilized bacterium was used for producing (S)-DCP. Investigations as well as production trials were performed on a 100 L and 5000 L scale. 

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To obtain reproducible antibiotic production by fermentation, it is necessary to obtain a pure culture of the producing organism. Pure cultures are isolated from mixed soil sample populations by various streaking and isolation techniques on nutrient media. Once a pure culture has been found that produces a new antibiotic typically on a mg/L scale, improvement in antibiotic yield is accompHshed by modification of the fermentation medium or strain selection and mutation of the producing organism. Production of g/L quantities may take years to accomplish. 

Tests were carried out as designated in ASTM Method D-925-83 related to staining of surfaces by contact, migration, or by diffusion. Hunter color values were measured on the L-scale. On this scale 100 is white and 0 is black. 

In fact viscosity reduction of diene elastomer blends with QDI show an optimum based on mixer discharge temperature. Figure 16.13 shows the results of two experiments done on the 16 L scale. The viscosities represent the viscosity of the fourth stage of a multistage mixing experiment. These compounds were 60/40 blends of either BR or SBR with NR and contained 50 phr of N-234 carbon black. 

Procedure 3 Synthesis of 6-Hydroxy Fluvastatin with M. rammaniana DSM 62752 in a BioWave Bioreactor on 22 L Scale... 

The synthesis of 6-hydroxy fluvastatin with M. rammaniana DSM 62752 gave high conversion (>95 %) in shake flask culture on 400 mL scale with 0.1 g L of fluvastatin as well as on 22 L scale in a Wave bioreactor-fed batch process at a final substrate concentration of 0.4 g L Instead of the partial purification by a second solid-phase extraction described above, 6-hydroxy fluvastatin can be obtained in high purity ( 95 %) by, for example, preparative medium-pressure liquid chromatography (MPLC) on RP18 silica gel. ... 

The core of double membrane stirrer perfusion bioreactors is a stirrer on which two microporous hollow fiber membranes are mounted, one of them being hydrophobic and used for bubble-free aeration, the second of them being hydrophilic and used for cell-free medium exchange [15]. This system has been reported to provide viable cell densities of 20 million cells per miUiliter for more than two months [106]. Although Lehmann et al. [15] have described the scale-up of this system to the 20-L and 150-L scale, it has been most commonly employed at the bench-scale. 

A study of substrate solubility and phase-partitioning behavior in a wide range of solvent concentrations by Truppo et al. led to a fourfold decrease in enzyme charge with an increase in product enantiomeric excess. The process was successfully run at 400-L scale yielding the desired product with 99.73%ee at 50% conversion with the optimized conditions [86]. The DP receptor antagonist 42 is being evaluated in clinical trials for the treatment of allergic rhinitis. 

A new microwave reactor for batchwise organic synthesis is described in Ref. 712 (Fig. 3.5). Its use permits us to carry out synthetic works or kinetic studies on the 20 100 m L scale, with upper operating limits of 260°C and 10 MPa (100 atm). Microwave-assisted organic reactions can be conducted safely and conveniently, for lengthy periods when required, and in volatile organic solvents. The use of water as a solvent is also explored [712]. 

K. Hodgins, L. Scale-Up Evaluations and Simulations of Mobility Control Foams for Improved Oil Recovery in Surfactants, Fundamentals and Applications in the Petroleum Industry, Schramm, L.L. (Ed.), Cambridge University Press Cambridge, 2000, pp. 251— 292. 

Fed-batch fermentations in PDU scale were made with two different S. cerevisiae strains, CBS 8066 and TMB 3000. Batch fermentations in a 2.5-L scale were done to compare the performance of batch and fed-batch procedures. 

Tetralone has been reduced to (7 )-1-tetralol with 166 at the 200-L scale (Scheme 12.65). The hydrogen source was /-PrOH. Initially, the maximum concentration to achieve high conversion was 0.05m in a closed system, but the ee decreased near the latter conversions. The key discovery in process optimization was removal of acetone by-product during the reaction. The catalyst is not stable at higher than 40°C however, the reaction can be performed under a slight vacuum (10-50 mbar) to remove acetone. Fresh IPA is added to the reaction to maintain constant volume. Under these conditions coupled with efficient agitation, substrate concentrations of 0.5m are achieved with complete conversions (TOF = 500-2500 Ir1) and reproducible enantioselectivity.212... 

L scaled distance between two planar surfaces L, L2 energy per unit volume m geometry index... 

These examples underline the potential of organocatalytic reactions for commercial scale applications. The scale up of the corresponding reactions ranges from L-scale applications to applications on a (pilot) production scale. In the following, several types of these reactions are discussed. 

When the enantioselective reduction of ethyl 4-chloroacetoacetate was carried out with alcohol dehydrogenase from Candida parapsilosis, the other enantiomer was produced ethyl (P)-4-chloro-3-hydroxybutanoate [134]. This product is a key intermediate in a synthesis of (R)-carnitine. In this case a substrate coupled approach was chosen. The enzyme also has a strong oxidation activity for 2-propanol, which was therefore selected as the cosubstrate. The situation is depicted in Fig. 3.50. Under optimized conditions, the yield of (R)-ethyl-4-chloro-3-hydroxy-butanoate reached 36.6 g L-1 (> 99% ee, 95% yield) on a 30 L scale. 

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