Analogues production

Kennedy, J., Murli, S. and Kealey, J.T. (2003) 6-Deoxyerythronolide B analogue production in Escherichia coli through metabolic pathway engineering. Biochemistry, 42, 14342. 

The compound 60 (C6S12) has been reported to be formed by reaction of the tetralithium salt 59 with sulfur monochloride at room temperature (Equation 4). In an alternative procedure, the tetrasodium salt was used. Similar procedures gave the CgSio and CgS analogues. Products were obtained as solvates and were not recrystallized <2005MCL575>. 

From an outsider s view of the pharmaceutical industry, this proliferation of products may be seen as an example of rampant commercialization. The analogue products are often regarded as me-too compounds - a term used pejoratively, notably by those who indulge in attacking the pharmaceutical industry, to suggest that because a pioneer medicine has proved to be commercially valuable, other companies want to share in the commercial success. Of course, companies must be commercially successful to stay in existence, as with any other business enterprise, but this cannot be the only basis for a new drug. As has been explained... 

In most processes, some expansion by puffing of the flow stream by water vapour pressure is required to achieve low-density expanded products. Bubble expansion has been comprehensively reviewed recently by Kokini and Moraru (2003). The extent and nature of expansion of the structures so formed are critical to their subsequent use and in-mouth texture. Highly expanded stmetures (0.1 g/ml), when eaten dry, give crisp textures, which melt in the mouth as plasticisation by saliva causes their cell walls to collapse. Hardness increases as bulk density increases, but many of the denser products are designed to be eaten in a rehydrated state as meat-like analogue products. Not surprisingly, the rate of stmeture collapse on hydration also increases as bulk density decreases, since these materials are both hydrophilic and porous. 

Figure 18.8. Meat analogue product from soya flour extrusion.

It is also possible to convert nonchiral readily available industrial organic chemicals into valuable chiral natural-analogue products. This is demonstrated by the conversion of achiral fumaric acid to L(-)-malic acid with fumarase as the active enzyme. The same compound is converted to the amino acid L(-h)-aspartic acid by Escherichia bacteria that contain the enzyme aspartase. If pseudomonas bacteria are added, another amino acid L-alanine is formed (Eq. 9.10). 

Fenthion, temephos and their degradation products were determined by HPLC-DAD and APCl-LC-MS in rice field water samples after SPE (Empore Cjg). Four fenthion transformation products could be identified in the positive or negative modes whereas the degradation of temephos resulted in six products. For both pesticides the oxo-analogue products predominate [366]. After rice fields had been treated with fenitrothion, crop waters were sampled and analysed by ELISA, LC-DAD and MS coupled by APCI interface. Eenitrothion, fenitrooxon, 3-methyl-4-nitrophenol and the s-Me isomer of fenitrothion were identified by LC-MS [367]. 

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