Synthesis enzymic reduction

Consonant with the present interest in chiral synthesis, two additional contributions can be cited. Sih al utilized a combined microbiological and organic chemical sequence in which key chirality establishing steps include the conversion of to chiral, but unstable, 18 by enzymic reduction using the fungus Diplodascus uninucleatus. Lower side-chain synthon was prepared by reduction of achiral with Pencillium decumbens. 

Enzyme reductions of carbonyl groups have important applications in the synthesis of chiral compounds (as described in Chapter 10). Dehydrogenases are enzymes that catalyse, for example, the reduction of carbonyl groups they require co-factors as their co-substrates. Dehydrogenase-catalysed transformations on a practical scale can be performed with purified enzymes or with whole cells, which avoid the use of added expensive co-factors. Bakers yeast is the whole cell system most often used for the reduction of aldehydes and ketones. Biocatalytic activity can also be used to reduce carbon carbon double bonds. Since the enzymes for this reduction are not commercially available, the majority of these experiments were performed with bakers yeast1 41. 

Proanthocyanidins and Procyanidins - In a classical study Bate-Smith ( ) used the patterns of distribution of the three principal classes of phenolic metabolites, which are found in the leaves of plants, as a basis for classification. The biosynthesis of these phenols - (i) proanthocyanidins (ii) glycosylated flavonols and (iii) hydroxycinnamoyl esters - is believed to be associated with the development in plants of the capacity to synthesise the structural polymer lignin by the diversion from protein synthesis of the amino-acids L-phenylalanine and L-tyro-sine. Vascular plants thus employ one or more of the p-hydroxy-cinnarayl alcohols (2,3, and 4), which are derived by enzymic reduction (NADH) of the coenzyme A esters of the corresponding hydroxycinnamic acids, as precursors to lignin. The same coenzyme A esters also form the points of biosynthetic departure for the three groups of phenolic metabolites (i, ii, iii), Figure 1. 

Tissue Cultures, Microbial Transformations.—Little success has rewarded the search for cell cultures that effectively biosynthesize monoterpenes de novo. The most impressive studies utilize cultures from a variety of Mentha spp. yields of oil were some 60 % (w/v) of those in the parent plants, but the monoterpene products were generally more oxidized (i.e. ketones extra C=C bonds predominated). In vitro, oxidation at C-3 of the menthane skeleton was also restricted, apparently owing to an inhibition of the enzymic reduction of the 4(8) double bond in the intermediates formed.925 926 Colchicine stimulated synthesis of essential oil by Mentha cultures.927 Iridoid glucosides have been produced by cultured cells of Gardenia spp.673 Menthone was biotransformed to neomenthol by Mentha suspension cultures,928 and Nicotiana lines oxidized linalool and its derivatives at C-10 to aldehydes and alcohols,929 and also foreign substrates such as a-terpineol (at C-6 and C-7) and /raw.s-/ -menthan-9-en-l-ol (at C-4 and C-10).930... 

Now it was possible to answer two further questions (a) which of C-18 or C-19 receives the hydride equivalent from NADPH and (b) from which face of NADPH 59 is the hydride delivered. The answer to (a) came from the synthesis of [4- H2]NADPH with 95 atom% H at C-4 59a, which was used for the enzymic reduction of precorrin-6A to yield H-labelled precorrin-6B. Analysis of this product by H-NMR and mass spectrometry then showed that the dl had been transferred solely to C-19 [94], Scheme 23. On mechanistic grounds, it seems certain that the transfer of the hydride ion occurs to the C-18 protonated form... 

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