Microbial deracemization of 1-aryl and 1-heteroaryl secondary alcohols.
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Alcohol Oxidoreductases↗
Biomedical subjects
A J Carnell
Publications and source records attributed to A J Carnell.
Stereoinversions using microbial redox-reactions.
This paper aims to provide a summary of the recent literature on the use of redox enzymes to carry out stereoinversion reactions on chiral secondary alcohols. Emphasis has been placed on biotransformations which result in the deracemization of a racemic substrate to give high value synthetic intermediates in a theoretical 100% yield. Most of the biocatalysts which are competent to carry out such transformations are whole cell systems, which contain the necessary cofactor recycling machinery to facilitate this otherwise entropically disfavoured process. The first section deals with deracemization of compounds such as mandelic acid and pantoyl lactone using two microorganisms which display enantiocomplementary stereospecificity. The deracemization of chiral alcohols such as beta-hydroxyesters, aryl ethanols and terminal 1,2-diols with single microorganisms will then be discussed and the influence of growth and reaction conditions on the selectivity observed will be emphasised. Then the ability of several microorganisms to deracemize by double stereoinversion substrates with two stereocentres such as cyclohexan-1,2-diol, cis and trans indan-1,2-diol and pentan-2,4-diol will be presented and some mechanistic rationale proposed. Lastly enzymes known as epimerases which are important in sugar and deoxysugar biosynthesis will be discussed with reference to some recent work on the mechanism of UDP-glucose epimerase.
Bacteria↗
Enadoline, a selective kappa-opioid receptor agonist shows potent antihyperalgesic and antiallodynic actions in a rat model of surgical pain.
Enadoline is a highly selective and potent kappa-opioid receptor agonist. This report describes and compares the activities of enadoline and morphine in a rat model of postoperative pain. A 1 cm incision through the muscle and skin of the plantar surface of the right hind paw induced thermal hyperalgesia as well as static and dynamic allodynia lasting at least 2 days. Postoperative testing was carried out using the plantar test for thermal hyperalgesia, von Frey hairs for static allodynia and light stroking with a cotton bud for dynamic allodynia. A single i.v. dose of enadoline 15 min before surgery dose-dependently (1-100 microg/kg) blocked the development of thermal hyperalgesia as well as static and dynamic allodynia for over 24 h with respective MEDs of < or = 1, 10 and 10 microg/kg. The administration of enadoline (100 microg/kg, i.v.), 1 h after surgery, completely blocked the maintenance of the hyperalgesic and allodynic responses, but its duration of action was much shorter (2 h) than when administered before surgery. Previous studies have shown that administration of morphine (1-6 mg/kg, s.c.) 0.5 h before surgery can prevent the development of thermal hyperalgesia with a MED of < or =1 mg/kg, but it has little effect on static allodynia. In the present study similar administration of morphine (1-3 mg/kg), unlike enadoline, had no effect on the development of dynamic allodynia. Morphine dose-dependently (1-6 mg/kg, s.c.) potentiated isoflurane-induced sleeping time and respiratory depression in the rat. However, whilst enadoline also (1-1000 microg/kg, i.v.) potentiated isoflurane-induced sleeping time, it did not cause respiratory depression. It is suggested that enadoline may possess therapeutic potential as a pre-emptive antihyperalgesic and antiallodynic agent.
Anesthesia Recovery Period↗