Enzyme-Based Organic Synthesis. Cheanyeh Cheng

Enzyme-Based Organic Synthesis - Cheanyeh Cheng


Скачать книгу
the immobilized ADH were 7.5 and 35 °C, respectively. Under the optimum conditions, the immobilized enzyme retained 58% of the original activity after 32 hours of incubation. The conversion of substrate (EOB) and the enantiomeric excess value of (S)‐product reached 88 and 99.2%, respectively, within two hours. The immobilized ADH retained about 42% of the initial activity after eight cycles [160]. Also, although the yields and the enantioselectivity are low to moderate, the enantioselective bioreduction of ethyl benzoylacetate and their p‐nitro and p‐methoxy substituted derivatives to form corresponding chiral ethyl 3‐hydroxy‐3‐phenylpropionate and substituted derivatives (Scheme 2.38) has long been of interest in pharmaceutical industry for synthesizing the key chiral building blocks of many compounds such as fluoxetine [161], chloramphenicol [162], and diltiazem [163]. However, the coupling of simple screening procedures and reaction engineering strategy can increase the (S)‐enantioselectivity to 99% e.e. and shows a significant improvement in the yields to around 85%. In this way, yeasts Pichia kluyveri, Pichia stipites, and Candida utilis were screened and better yields and e.e.’s for ethyl benzoylacetate, p‐nitrobenzoylacetate, and p‐methoxybenzoylacetate can be achieved by the addition of glucose, α‐chloroacetophenone as inhibitor, and immobilization of the yeast in alginate beads, respectively. These processes can also be implemented on a preparative scale and still maintain the same yield and e.e. [164].

Chemical reaction depicting yeast mediated enantioselective reduction of ethyl benzoylacetate and substituted derivatives.

      The ADH obtained from Thermus sp. ATN1 (TADH) is an NAD(H)‐dependent enzyme, which shows a very broad substrate spectrum including aldehydes, aliphatic ketones, cyclic ketones, and double‐ring systems and produces exclusively the (S)‐enantiomer in high enantiomeric excess (>99%) for ketones. TADH can be used in the presence of 10% (v/v) water‐miscible solvents like 2‐propanol or acetone, which plays as sacrificial substrate in substrate‐coupled cofactor regeneration reactions. TADH retained 80% of its activity when water‐insoluble solvent like hexane or octane is used as cosolvent that forms an aqueous/organic biphasic reaction medium to allow the reaction of low‐water‐soluble substrates [169].

Chemical reaction depicting asymmetric reduction of ketones and polymerization of the optically pure monomers for application in material chemistry.

      2.2.2 Reduction of C═C Bonds


Скачать книгу