Alcohols enzymatic transformations

Fermentation An anaerobic bioprocess. An enzymatic transformation of organic substrates, especially carbohydrates, generally accompanied by the evolution of gas as a byproduct. Fermentation is used in various industrial processes for the manufacture of products (e.g., alcohols, organic acids, solvents, and cheese) by the addition of yeasts, moulds, and bacteria. 

Enantioselective Enzymatic Transformations of Alcohols 153 - y NHCbz Lipase, VA AcO>> - " y< NHCbz... 

In this enzymatic transformation, three optically active compounds were prepared in one step. Besides the enantiomerically enriched hydroperoxide (5)-16/17a, also the opposite enantiomer of the corresponding alcohol (/f)-19/18a and enantiomerically enriched (S)-sulfoxide 23 could be isolated (equation 13). 

Together with fermentation, both the prefermentative and simultaneous maceration influences the supply of essential yeast nutrients and substrates for their enzymatic transformation. The release of nutrients from the pomace is also under the influence of heat and alcohol, generated by yeast metabolism. 

It is worth mentioning the emergence of sequential catalytic processes involving a ruthenium-catalyzed step followed by a catalytic enzymatic transformation. This strategy has been developed by the groups of J.E. Backvall, and M.-J. Kim and J. Park especially for the dynamic kinetic resolution of alcohols (Scheme 50) [107-109]. 

Surprisingly, the introduction of the pyridine ring not only influences the velocity of the enzymatic transformations, but also induces promising stereochemical effects (Table 1). For instance, at 40% conversion (R)-phenylethanol is obtained from the pyridyl acetate 25 with 73 % ee, whereas the value for the corresponding phenylacetate is only 28%. Also, the secondary alcohol liberated from the ester 26 displays 98% ee at 40% conversion, whereas the respective phenylacetate leads to 1-phenylpropanol with 94% ee but at a conversion rate of 12% only [19,20]. These results demonstrate that the stereoselecting properties of penicillin acylase may be enhanced by appropriate engineering of the substrate. This is of particular interest since this enzyme has already been used for the kinetic resolution of various chiral alcohols [21-24], e.g. furyl alkyl carbinols [24], which are valuable precursors for the de novo synthesis, with moderate to high ee values, of carbohydrates. 

Problem 15.5 The isopentyl and active amyl alcohols are formed by enzymatic transformation of the amino acids leucine and isoleucine, which come from hydrolysis of protdn material in the starch. 

The plasma membrane contains the phospholipid phosphatidyl inositol (Ptdlns), in which the phosphate group is esterified with a cyclic alcohol, myo-D-inositol (Fig. 6.4). Starting from Ptdlns, a series of enzymatic transformations lead to the generation of a diverse number of second messengers. Ptdlns is first phosphorylated by specific kinases at the 4 and 5 positions of the inositol residue, leading to the formation of phosphatidyl inositol-4,5-bisphosphate [PtdIns(4,5)P2]. 

Figure 16.4-4. Enzymatic transformation of (Z,Z)-n°na-2,4-dienal to the corresponding alcohol and acid catalyzed by an alcohol and an aldehyde dehydrogenase from yeast.

Enzymes are an increasingly available and important tool in the arsenal of the synthetic chemist. Enzymatic reductions are often straightforward and highly stereoselective. There are now many enzymatic transformations that are compatible with the use of organic solvents.6l5 Other solvents can be used as well, illustrated by the enzyme alcohol dehydrogenase from Geotrichum candidum, which is active in supercritical carbon dioxide.6i6 Prelog studied the reduction of ketones with several enzymatic systems. Reduction of... 

Enantiomerically pure 4-alkyl substituted derivatives of tryptophan required for the asymmetric syntheses of ergot alkaloids has been obtained [35]. The author used the method [36] to produce 4-alkyl substituted indoles and combined this organometallic reaction with an enantioselective enzymatic transformation. An efficient eight stage synthesis ofN-benzenesulphonyl-3-(3 -methoxyprop-2 -en-r-yl)-4-(r-hydroxy-2 -trimethylsilymethyl-prop-2 -en-r-yl)-indoles from 4-carbomethoxyindole has been described [37]. The use of these benzylic alcohols for intramolecular cation-olefine cycloadditions yielding either a tetracyclic or a tricyclic product was also demonstrated. 

Stereoinversion Stereoinversion can be achieved either using a chemoenzymatic approach or a purely biocatalytic method. As an example of the former case, deracemization of secondary alcohols via enzymatic hydrolysis of their acetates may be mentioned. Thus, after the first step, kinetic resolution of a racemate, the enantiomeric alcohol resulting from hydrolysis of the fast reacting enantiomer of the substrate is chemically transformed into an activated ester, for example, by mesylation. The mixture of both esters is then subjected to basic hydrolysis. Each hydrolysis proceeds with different stereochemistry - the acetate is hydrolyzed with retention of configuration due to the attack of the hydroxy anion on the carbonyl carbon, and the mesylate - with inversion as a result of the attack of the hydroxy anion on the stereogenic carbon atom. As a result, a single enantiomer of the secondary alcohol is obtained (Scheme 5.12) [8, 50a]. 

Interestingly, for the transformation of both the racemic 1-hydroxyalkanephosphonates 41 and 2-hydroxyalkanephosphonates 43 into almost enantiopure acetyl derivatives 42 and 44, respectively, a dynamic kinetic resolution procedure was applied. Pamies and BackvalP used the enzymatic kinetic resolution in combination with a ruthenium-catalysed alcohol racemization and obtained the appropriate O-acetyl derivatives in high yields and with almost full stereoselectivity (Equation 25, Table 5). It should be mentioned that lowering... 

During the past few years, increasing numbers of reports have been published on the subject of domino reactions initiated by oxidation or reduction processes. This was in stark contrast to the period before our first comprehensive review of this topic was published in 1993 [1], when the use of this type of transformation was indeed rare. The benefits of employing oxidation or reduction processes in domino sequences are clear, as they offer easy access to reactive functionalities such as nucleophiles (e. g., alcohols and amines) or electrophiles (e. g., aldehydes or ketones), with their ability to participate in further reactions. For that reason, apart from combinations with photochemically induced, transition metal-catalyzed and enzymatically induced processes, all other possible constellations have been embedded in the concept of domino synthesis. 

A classical approach to driving the unfavorable equilibrium of an enzymatic process is to couple it to another, irreversible enzymatic process. Griengl and coworkers have applied this concept to asymmetric synthesis of 1,2-amino alcohols with a threonine aldolase [24] (Figure 6.7). While the equilibrium in threonine aldolase reactions typically does not favor the synthetic direction, and the bond formation leads to nearly equal amounts of two diastereomers, coupling the aldolase reaction with a selective tyrosine decarboxylase leads to irreversible formation of aryl amino alcohols in reasonable enantiomeric excess via a dynamic kinetic asymmetric transformation. A one-pot, two-enzyme asymmetric synthesis of amino alcohols, including noradrenaline and octopamine, from readily available starting materials was developed [25]. 

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