L-DOPA. See

The physical and chemical behavior of molecules is largely determined by their constitution (the type and number of the atoms they contain and their bonding). Structural formulas can therefore be used to predict not only the chemical reactivity of a molecule, but also its size and shape, and to some extent its conformation (the spatial arrangement of the atoms). Some data providing the basis for such predictions are summarized here and on the facing page. In addition, L-dihy-droxyphenylalanine (L-dopa see p.352), is used as an example to show the way in which molecules are illustrated in this book. 

Reaction 9.1 has been extensively studied to establish the mechanism of asymmetric hydrogenation. The catalytic cycle proposed for the asymmetric hydrogenation of the methyl ester of a-acetamido cinamic acid with 9.14 as the precatalyst is shown in Fig. 9.3. As mentioned earlier, this reaction is one of the early examples of industrial applications of asymmetric catalysis for the manufacture of L-DOPA (see Table 1.1). 

The first industrially interesting production of a chiral pharmaceutical with a chiral metal complex catalyst is the asymmetric hydrogenation of cinnamic acid derivatives to give L-DOPA, see Fig. 6.21. 

Fig. 7. Depiction of the hypothetical relationship between the locus of DA depletion in cortico-striatal loops , cognitive and motor performance and the effects of L-Dopa (see Swainson et al., 2000 Cools et al., 2001). Whereas some forms of cognitive performance are improved by L-Dopa in Parkinson s disease, reversal learning is impaired- possibly as a consequence of the ventral cortico-striatal loops being less severely depleted than the more dorsal loops , thus leading to effective over-dosing of this circuitry by L-Dopa. Adapted from Swainson et ah (2000).

METHYLDOPA see DNA800 a-METHYL-l-DOPA see DNA800 1-a-METHYLDOPA see DNA800 METHYL DURSBAN see CMA250 METHYL-E 605 see MNHOOO METHYLE (ACETATE de) (FRENCH) see MFWIOO 0,0-METHYLEEN-BIS(4-CHL00RFEN0L) see MJM500... 

A small subset of patients with hyperphenylalaninemia show an appropriate reduction in plasma phenylalanine levels with dietary restriction of this amino acid however, these patients still develop progressive neurologic symptoms and seizures and usually die within the first 2 years of life ("malignant" hyperphenylalaninemia). These infants exhibit normal phenylalanine hydroxylase (PAH) activity but have a deficiency in dihy-dropteridine reductase (DHPR), an enzyme required for the regeneration of tetrahydro-biopterin (BH4), a cofactor of PAH (see Fig. 39.18). Less frequently, DHPR activity is normal but a defect in the biosynthesis of BH4 exists. In either case, dietary therapy corrects the hyperphenylalaninemia. However, BH4 is also a cofactor for two other hydroxy-lations required in the synthesis of neurotransmitters in the brain the hydroxylation of tryptophan to 5-hydroxytryptophan and of tyrosine to L-dopa (see Chapter 48). It has been suggested that the resulting deficit in central nervous system neurotransmitter activity is, at least in part, responsible for the neurologic manifestations and eventual death of these patients. 

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