3.4- Dihy droxyphenylalanine

Mechanism of Action A depigmenting agent that suppresses melanocyte metabolic processes of the skin. Inhibits the enzymatic oxidation of tyrosine to DOPA (3,4-dihy-droxyphenylalanine). Sun exposure reverses this effect and causes repigmentation. Therapeutic Effect Lightens hyperpigmented areas. 

The racemic laudanosine (7g) syntheses were referred to earlier in The Alkaloids (Vol. XII, p. 348). From the racemic mixture it is difficult to obtain (S)-(+)-laudanosine which is widely distributed in nature. The synthesis of its unnatural (R )-form (in poor yields) has been reported (asymmetric reduction of 3,4-dihydropapaverine with lithium butyl-(hydro)dipinan-3a-y borate) (363). Recently, a description of the biogenetic synthesis of these two forms from methyl-L-(+)-3,4-dihy-droxyphenylalaninate hydrochloride by condensation with sodium 3-(3,4-dimethoxyphenyl)glycinate at pH 4 and 35° was given. Thus, a dia-stereoisomeric mixture of the Pictet-Spengler products 11a and lib (ratio... 

However, of industrial importance is the manufacturing of (L)-3,4-dihy-droxyphenylalanine ((L)-DOPA), an agent against Parkinson s disease, using a tyrosine phenol-lyase. Ajinomoto employs a whole-cell preparation from Er-winia herbicola to obtain the target compound in a three-component reaction, starting from catechol, pyruvic acid and ammonia. The annual capacity amounts to around 250 tonnes. [64]... 

C. J. Hawkins, M. F. Lavin, D. L. Parry and I. L. Ross, Isolation of 3,4-Dihy-droxyphenylalanine-Containing Proteins Using Boronate Affinity-Chromatography, A aZ. Biochem., 1986,159(1), 187-190. 

Figure 5. Hydroxylation of L-tyrosine to L-3,4-dihy-droxyphenylalanine (A) and conversion of 4-hydroxy-phenylacetic acid to 3,4-dihydroxyphenylacetic acid by Klebsiella oxytoca (B) (64).

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. 

Kinetic enhancement was evidenced through enantios-electivity in catecholase activity. Aerobic kinetic experiments with chiral catechols such as l and d-DOPA (dihy-droxyphenylalanine) showed enantioselectivity related to a difference in the binding constants of the two enantiomers. Anaerobic 1 1 binding isotherms with various amino acids... 

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