Chorismic acid preparation

Chloramphenicol, an antibiotic built in Streptomyces species (E 5.2), is formed from chorismic acid probably by the pathway given in Fig. 146. It is widely used in medicine. Today it is prepared synthetically. 

Beginning with erythrose, shikimic acid is prepared, and it is converted to chorismic acid (a.k.a., chorismate). 

Hydroxybenzoic acid 5.35) has been shown to stand as the key intermediate in ubiquinone biosynthesis, in living systems from micro-organisms to mammals. In animals, phenylalanine and tyrosine serve as precursors, but in bacteria chorismic acid 5.10) is the precursor [28, 29]. Interlocking evidence obtained from bacteria in experiments with mutants (and genetic analysis), cell-free preparations, and isolation and identification of intermediates allows clear delineation [25, 29] of the sequence of biosynthesis as that shown in part in Scheme 5.5 beyond 5.35) the intermediates are the... 

An unsaturated anhydroaldonic acid prepared during a study of the rearrangement of chorismic acid analogues is discussed in Chapter 13, and some epoxyaldonolactones are mentioned in Chapter 5. 

In cell cultures of Catharanthus roseus 2,3-DHBA was found to be produced after elicitation of the cells with fungal cell-wall preparations [40,41]. The production of this compound in cell cultures was paralleled by an increase in the activity of the enzyme isochorismate synthase [40]. Although direct evidence for the intermediacy of iso-chorismate is not yet reported, it seems that the isochorismate biosynthetic pathway for benzoic acid derivatives can also be found in plants. 

When we began our synthetic program, shikimic acid had been prepared by a number of routes, and the groups of Danishefsky and Plieninger had reported syntheses of prephenic acid. The intervening intermediates, shikimate-3-phosphate (S-3-P), 5-enolpyruvylshikimate-3-phosphate (EPSP), and chorismate, were only available from natural sources or by enz)onatic transformations. 

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