Enzymatic manufacturing process

Scheme 7. Enzymatic manufacturing process for intermediate 24. Table 1. Green chemistry metrics for scale-up of 24.

Insulin was originally (since the 1930s) obtained from porcine and bovine extracts. Bovine insulin differs from human insulin by three amino acids, and it can elicit an antibody response that reduces its effectiveness. Porcine insulin, however, differs in only one amino acid. An enzymatic process can yield insulin identical to the human form. Currently, insulin is produced via the rDNA process it was the first recombinant biopharmaceutical approved by the FDA in 1982. The recombinant insulin removes the reliance on animal sources of insulin and ensures that reliable and consistent insulin is manufactured under controlled manufacturing processes. A description of diabetes meUitus and insulin is presented in Exhibit 4.13. 

Figure S. A diagrammatic illustration of the manufacturing processes fm LMWHs. Uniractionated hqrarin of pOTcine or bovine origin is depolymerized by chemical or enzymatic digestion in controlled ccmditimis. The degree of depolymerization is adjusted to obtain LMWH of varying weight...

Esterases, lipases, and proteases are widely used in enzymatic resolution processes of racemic carboxy acid ester substrates. Industrially relevant examples are the manufacture of D-)ff-acetylmercaptoisobutyric acid, the optically active side-chain of the ACE inhibitor captopril (43) [104] (Scheme 26), and synthesis... 

Complex flavours made by biotechnical manufacturing processes are borderline products between natural and nature-identical flavours. The declaration of complex biotechnical flavours is Flavour Preparations . For the manufacturing of those biotechnical steps (enzymatic and microbiological processes) are explicitly approved. There is still some uncertainty, however, with the declaration regarding the origin of the starting materials for the biotechnical reaction and the difficult analytical discemabil-ity between physically extracted and biotechnically produced flavours from plant and animal raw materials. 

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. 

Biocatalytic process Enzymes in production Enzymatic manufacture... 

The composition of tea-leaf varies with climate, season, horticultural practices, variety of the plant, and age of the leaf, i.e., the position of the leaf on the harvested shoot. Three main varieties of the commercial tea are available green (unfermented). Oolong (partially fermented), and black (fully fermented). Their composition varies according to the manufacturing process, which differs in the degree of enzymatic oxidation or... 

The protein contaminants in benzylpenicillin derive from the fermentation manufacturing processes used in production of the antibiotic. During the course of fermentation, proteins of the medium become penicilloylated and may be extracted in minute amounts into the final preparations. The semisynthetic penicillins are prepared from 6-APA, which in turn is obtained through either enzymatic or chemical removal of the side chain in benzylpenicillin (Carrington 1971). Penicil-... 

Surfactants containing perfluoroalkyl groups (fluo-rinated surfactants) play an important role in different manufacturing processes (metal working, the photo industry, etc.). They are generally considered as being very stable compounds because the enzymatic cleavage of the carbon-fluorine bond is very hard to achieve. This is confirmed by the behaviour of perfluorooctane... 

For small-scale chemistry, the practical value of the specificity and selectivity inherent in enzymatic catalysis is increasingly recognized. The topic is the subject of a number of recent books (see the Bibliography at the end of each chapter), and the current literature is full of examples. There may be some resistance to the large-scale use of enzymes, but there are now enough manufacturing processes in operation to demonstrate the effectiveness of the technology. 

Improved efficiency in the synthesis of 24 was ultimately achieved via an enzymatic desymmetrization approach (Scheme 7). In the key step of this route, an asymmetric oxidation of achiral amine 41 promoted by monoamine oxidase (MAON) under an oxygen atmosphere afforded intermediate 42. In this streamlined process, sodium bisulfite was included in the enzymatic oxidation mixture to effect direct conversion to sulfonate 44. Treatment of 44 with sodium cyanide provided the trans-nitrile 43 as a single diastereomer in approximately 90% yield from pyrrolidine 41. As in the second-generation synthesis, the nitrile is hydrolyzed to the methyl ester under Pinner conditions (HCI, methanol). In the manufacturing process, the product was converted to its free base using NaOH, then crystallized as the HCI salt from i-propanol and methyl t-... 

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