Use in amino acid synthesis

The nucleophilic carbon centres of lithium enolates may also be pyrami-dalized, though there is little experimental evidence of this (Seebach et al., 1985, 1991). Silyl enol ethers are generally planar, but two (67 R = Ph and OMe] derived from an imidazolidinone used in amino acid synthesis show... 

N-Acetyl and N-benzoyl derivatives may be readily prepared from the corresponding acid chloride or, in the case of acetyl derivatives, acetic anhydride. General procedures are detailed in Sections 9.6.21, p. 1273, and 9.6.23, p. 1279, and the use of /V-acetyl derivatives in amino acid synthesis is to be found, for example, in Expts 5.183 and 5.184. 

The application of isolated enzymes to preparative organic synthesis on an industrial scale is a matter of active research worldwide. Since the late sixties, immobilized enzymes have been used in amino acid production in continuous processes on a large scaled 2. In the late seventies, the use of soluble enzymes, especially in membrane reactors, broadened the scope of enzyme technology13, 41 and opened the way to simultaneous use of more than one enzyme for complex conversions -especially coenzyme-dependent biotransformations[5-7. In the early 1980s the use of enzymes was extended further to involve organic solvents[8, 9 ... 

Overall, in a transamination reaction, an amino group from one amino acid becomes the amino group of a second amino acid. Because these reactions are readily reversible, they can be used to remove nitrogen from amino acids or to transfer nitrogen to a-keto acids to form amino acids. Thus, they are involved both in amino acid degradation and in amino acid synthesis. 

The specific rotation of amino acids in aqueous solution is strongly influenced by pH. It passes through a minimum in the neutral pH range and rises after addition of acids or bases (Table 1.3). There are various possible methods of separating the racemates which generally occur in amino acid synthesis (cf. 1.2.5). Selective crystallization of an over-saturated solution of racemate after seeding with an enantiomer is used, as is the fractioned crystallization of diastereomeric salts or other derivatives,... 

The overall schematic representation of these reactions is shown in Figure 17. Acetyl-CoA mixes with the acetyl-CoA derived from other metabolic pathways, such as the oxidative decarboxylation of pyruvate or from amino-acid metabolism. However, it seems that acetyl-CoA derived from fatty acid oxidation is not used in fatty acid synthesis since fatty acyl derivatives of CoASH may act as feed-back regulators of fatty acid synthesis. 

The use of transition-metal complexes to activate haloarenes for S Ar reactions has been used as a strategy for important skeletal bond formation steps in a number of syntheses. An example of carbon-carbon bond formation in this way can be found in amino acid synthesis. The Shiffs base nucleophile (Me02C)(Ph2C=N)CH displaces fluorine from (fluorotoluene)Cr(CO)3 [316]. This type of substitution reaction has been applied in a model study for the diaryl ether section of SK F L-94901 (68) using a cationic cyclohexadienyliron complex (see Scheme 14.16)... 

Miscellaneous Reactions. Sodium bisulfite adds to acetaldehyde to form a white crystalline addition compound, insoluble in ethyl alcohol and ether. This bisulfite addition compound is frequendy used to isolate and purify acetaldehyde, which may be regenerated with dilute acid. Hydrocyanic acid adds to acetaldehyde in the presence of an alkaU catalyst to form cyanohydrin the cyanohydrin may also be prepared from sodium cyanide and the bisulfite addition compound. Acrylonittile [107-13-1] (qv) can be made from acetaldehyde and hydrocyanic acid by heating the cyanohydrin that is formed to 600—700°C (77). Alanine [302-72-7] can be prepared by the reaction of an ammonium salt and an alkaU metal cyanide with acetaldehyde this is a general method for the preparation of a-amino acids called the Strecker amino acids synthesis. Grignard reagents add readily to acetaldehyde, the final product being a secondary alcohol. Thioacetaldehyde [2765-04-0] is formed by reaction of acetaldehyde with hydrogen sulfide thioacetaldehyde polymerizes readily to the trimer. 

These two methods ate popular for a-amino acid synthesis, and used in the industrial production of some amino acids since taw materials are readily available. 

The synthesis of an a-amino acid from an achiral precursor by any of the methods described in the previous section yields a racemic mixture, with equal amounts of S and R enantiomers. To use an amino acid in the laboratory synthesis of a naturally occurring protein, however, the pure S enantiomer must be obtained. 

Compounds of special interest whose preparation is described include 1,2,3-benzothiadiazole 1,1-dioxide (a benzyne precursor under exceptionally mild conditions), bis(l,3-diphenylimida-zolidinylidene-2) (whose chemistry is quite remarkable), 6- di-melhylamino)julvene (a useful intermediate for fused-ring non-benzenoid aromatic compounds), dipkenylcyclopropenone (the synthesis of which is a milestone in theoretical organic chemistry), ketene di(2-melhoxyethyl) acetal (the easiest ketene acetal to prepare), 2-methylcyclopenlane-l,3-dione (a useful intermediate in steroid synthesis), and 2-phenyl-5-oxazolone (an important intermediate in amino acid chemistry). 

In a survey of the methods used for peptido synthesis in 1968, the isoxazolium salt method was used in 7% of the examples surveyed J. H. Jones in Amino Acids, Peptides, and Proteins, Vol. 2, The Chemical Society, London, 1970, p. 145. 

Consider one small molecule, phenylalanine. It is an essential amino acid in our diet and is important in protein synthesis (a component of protein), as well as a precursor to tyrosine and neurotransmitters. Phenylalanine is one of several amino acids that are measured in a variety of clinical methods, which include immunoassay, fluorometry, high performance liquid chromatography (HPLC see Section 4.1.2) and most recently MS/MS (see Chapter 3). Historically, screening labs utilized immunoassays or fluorimetric analysis. Diagnostic metabolic labs used the amino acid analyzer, which was a form of HPLC. Most recently, the tandem mass spectrometer has been used extensively in screening labs to analyze amino acids or in diagnostic labs as a universal detector for GC and LC techniques. Why did MS/MS replace older technological systems The answer to this question lies in the power of mass spectrometer. 

Prior to their work with the Strecker reaction the Jacobsen group reported a combinatorial approach to the discovery of coordination complexes (29). A modular approach was taken in the synthesis of libraries of potential ligands for transition metals. Four variable components were used. Two amino acids were placed at positions 1 and 2, with a turn element connecting these groups (Scheme 9). The... 

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