Aldol reaction biological example

The interest in the mechanisms of SchifF base hydrolysis stems largely from the fact that the formation and decomposition of SchifF base linkages play an important role in a variety of enzymatic reactions, for example, carbonyl transfers involving pyridoxal phosphate, aldol condensations, /3-decarboxylations and transaminations. The mechanisms for the formation and hydrolysis of biologically important SchifF bases, and imine intermediates, have been discussed by Bruice and Benkovic (1966) and by Jencks (1969). As the consequence of a number of studies (Jencks, 1959 Cordes and Jencks, 1962, 1963 Reeves, 1962 Koehler et al., 1964), the mechanisms for the hydrolysis of comparatively simple SchifF bases are reasonably well understood. From the results of a comprehensive kinetic investigation, the mechanisms for the hydrolysis of m- and p-substituted benzylidine-l,l-dimethylethylamines in the entire pH range (see, for example, the open circles in Fig. 13) have been discussed in terms of equations (23-26) (Cordes and Jencks, 1963) ... 

CoA and oxaloacetate. Actually, this is another biological example of an aldol condensation reaction. It is catalyzed by the enzyme citrate synthase. The product that is formed is citrate ... 

An example of Claisen reaction is provided by the first step in the biosynthesis of cholesterol and terpenes, which starts from acetyl-CoA. Similar to the Claisen condensation, 2equiv of acetyl-CoA couple to acetoacetyl-CoA, which represents a biological analog of acetoacetate. Following the pattern of an aldol reaction, acetoacetyl-CoA reacts with another equivalent of acetyl-CoA as a carbon nucleophile to give p-hydroxy-p-methylglutaryl-CoA (Figure 1.20). 

Addition of Phosphorus Nucleophiles to Imines As the Pudovik and the Abramov reactions constitute phosphorus analogs of the aldol reaction, there is also a phosphorus equivalent for the Mannich reaction, namely, the Kabachnik-Fields reaction (see Scheme 47.7). In this process, phosphorus nucleophiles add to imines to produce a-aminophosphonate derivatives, which can be considered amino acid analogs. These compounds by themselves, or when incorporated into short peptides, find applications as enzyme inhibitors or as antibacterial and antifungal agents. However, in only a few instances were optically pure derivatives prepared for biological and pharmaceutical applications. Examples include the synthesis of antibiotic ala-fosfalin 82, penicillopepsin 83, and HIV protease... 

Another impressive example of dienamine-iminium cascade catalysis was developed during the total synthesis of a-tocopherol 59 by Liu et al. [31]. This natural product is a member of the vitamin E family and possesses remarkable biological activity. The key step in the total synthesis of this natural product involved an organocatalytic aldol/oxa-Michael cascade reaction for construction of the core... 

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