4- Amino-3-hydroxycinnamic acid

Proanthocyanidins and Procyanidins - In a classical study Bate-Smith ( ) used the patterns of distribution of the three principal classes of phenolic metabolites, which are found in the leaves of plants, as a basis for classification. The biosynthesis of these phenols - (i) proanthocyanidins (ii) glycosylated flavonols and (iii) hydroxycinnamoyl esters - is believed to be associated with the development in plants of the capacity to synthesise the structural polymer lignin by the diversion from protein synthesis of the amino-acids L-phenylalanine and L-tyro-sine. Vascular plants thus employ one or more of the p-hydroxy-cinnarayl alcohols (2,3, and 4), which are derived by enzymic reduction (NADH) of the coenzyme A esters of the corresponding hydroxycinnamic acids, as precursors to lignin. The same coenzyme A esters also form the points of biosynthetic departure for the three groups of phenolic metabolites (i, ii, iii), Figure 1. 

Phenolic acids are rarely present as free forms, except in processed food, but occur more frequently as soluble or insoluble esters. These esters are formed with polysaccharides or simple sugars, with quinic acid or other carboxylic acids such as tartaric or shikimic acids [Herrmann, 1989], with other phenolic acids, with lipids [Clifford, 2000], with sterols or glycerol [Clifford, 1999], or with amino acids [Clifford and Knight, 2004], To quinic acid, they can be conjugated as mono-, di-, tri-, and tetra-esters [Clifford, 2000]. The multiple esters can contain the same or different hydroxycinnamic acids. Among the hydroxycinnamic conjugates, caffeoylquinic and di-caffeoylquinic acids... 

Figure 3. MALDI-TOF mass spectrometry of peaks 1 (A-C) and 2 (D-F) purified after digestion of PVDF-bound transferrin using 1% RTX-100 (A, D), octylglucopyranoside (B, E), and decylglucopyranoside (C, F) as shown in Figure 2. Approximately 0.5% of the purified peptide (-150 fmole) was mixed with alpha-cyano-4-hydroxycinnamic acid and analyzed by MALDI-TOF mass spectrometry as described in Materials and Methods. Ninety percent of the peptide was amino terminally sequenced (Table II).

Biosynthesis. The primary precursors of L. are con-iferyl, sinapyl and p-coumaiyl alcohoi, which are derived from 4-hydroxycinnamic acid. L. from conifers (i. e. from softwood) is derived chiefly from conifeiyl alcohol with variable but small proportions of sinapyl and p-coumaryl alcohol. L. from dicotyledonous an-giosperms (i.e. from hardwood), particularly deciduous trees, is formed chiefly from sinapyl (-44%) and coniferyl (-48 %) alcohol, with about 8 % p-cou-maryl alcohol. L. in grasses is formed from p-coumar-yl (-30%), coniferyl (-50%) and sinapyl (-20%) alcohol. These primary L. precursors are formed from the aromatic amino acids L-phenylalanine and L-tyro-sine by a series of reactions shown (Rg.). The first reaction is catalysed by L-Phenylalanine ammonia-lyase (EC 4.3.1.5) (see) this enzyme is induced by light in a process involving phytochrome, and it is of general importance in the synthesis of plant phenolic compounds from phenylalanine and tyrosine. 

Apart from cinnamoyl esters, aromatic amino acids (see Chap. 5.1) and the alcohols corresponding to the common hydroxycinnamic acids, as well as some glycerolaryl compounds, are of interest in connection with the biosynthesis of lignin and other polycyclic phenolic compounds. 

Fig. 1. Schematic representation for the three main CA inhibition mechanisms (A) Sulfonamides (and their isosteres, sulfamate, and sulfamide) substitute the fourth zinc ligand and bind in tetrahedral geometry of the metal ion (Alterio et al., 2009) (B) Inorganic anion inhibitors (thiocyanate as an example) add to the metal ion coordination sphere leading to trigonal bipyramidal adducts (Alterio et al., 2009) (C) Phenols anchor to the Zn(II) coordinated water molecule/hydroxide ion (Nair et al., 1994) (D) Coumarins (hydrolyzed in situ to 2-hydroxycinnamic acids) occlude the entrance of the active site cavity, interacting both with hydrophilic and hydrophobic amino acid residues. The inhibitor does not interact at all with the catalytically crucial Zn(II) ion which is coordinated by three His residues and a water molecule (Maresca et al, 2009 Maresca et al., 2010).

Figure 8. Initially envisioned biosynthetic pathway p-amino acid component of C-1027 invoking SgcC4 as an aminomutase capable of converting L-tyrosine into tyrosine. Central to the hypothesis was transient production of p-hydroxycinnamic acid (HCA, 15).

Kinsel, G. R. Yao, D. Yassin, F. H. Marynick, D. S. Equilibrium conditions in laser desorbed plumes Thermodynamic propertues of aIpha-cyano-4-hydroxycinnamic acid and protonation of amino acids. Eur. J. Mass Spectrom. 2006, 12, 359-367. 

Gallic acid is almost invariably found in plant tissues in ester form (109). Various simple esters of gallic acid have been described from plant sources (Table 1 and Table 5) and these metabolites are in many ways analogous to the hydroxycinnamoyl esters occurring in plants (31). These esters are thus formed by association with sugars, polyols, glycosides and other phenols. In contrast to the hydroxycinnamic acids however (100), fully authenticated examples of the occurrence of N-acyl derivatives (with amines, amino-acids and alkaloids) of gallic acid have not yet been described in the literature. 

Some of the pathways of animal and bacterial metabolism of aromatic amino acids also are used in plants. However, quantitatively more important are the reactions of the phenylpropanoid pathway,173-1743 which is initiated by phenylalanine ammonia-lyase (Eq. 14-45).175 As is shown at the top of Fig. 25-8, the initial product from phenylalanine is trails-cinnam-ate. After hydroxylation to 4-hydroxycinnamate (p-coumarate) and conversion to a coenzyme A ester,1753 the resulting p-coumaryl-CoA is converted into mono-, di-, and trihydroxy derivatives including anthocyanins (Box 21-E) and other flavonoid compounds.176 The dihydroxy and trihydroxy methylated products are the starting materials for formation of lignins and for a large series of other plant products, many of which impart characteristic fragrances. Some of these are illustrated in Fig. 25-8. 

The shikimate/arogenate pathway leads to the formation of three aromatic amino acids L-phenylalanine, L-tyrosine, and L-tryptophane. This amino acids are precursors of certain homones (auxins) and of several secondary compounds, including phenolics [6,7]. One shikimate/arogenate is thought to be located in chloroplasts in which the aromatic amino acids are produced mainly for protein biosynthesis, whereas the second is probably membrane associated in the cytosol, in which L-phenylalanine is also produced for the formation of the phenylpropanoids [7]. Once L-phenylalanine has been synthesized, the pathway called phenylalanine/hydroxycinnamate begins, this being defined as "general phenylpropanoid metabolism" [7]. 

Methyl-3-amino-4-hydroxycinnamate. The nitro ester was reduced with Na2S204 using the same procedure as for the corresponding acid. Chloroform instead of ether was used as extractant. Recrystallization employed a 1 4 mixture of CH3OH in CCI4 to give a white powder (64% yd) m.p. 146-147 . 

Methyl-4-amino-3-hydroxycinnamate. Reduction of the nitro compound was carried out as described for the acid except that the reaction temperature was maintained at 55 for 45 min. Extraction with CHCI3 gave a light yellow solid which was recrystallized from 1 4 CH OH in CCI4 to give a light brown solid (60% yd) m.p. 145-1460. 

---