Tryptophan Cinchona

The most successful modifier is cinchonidine and its enantiomer cinchonine, but some work in expanding the repertoire of substrate/modifier/catalyst combinations has been reported (S)-(-)-l-(l-naphthyl)ethylamine or (//)-1 -(I -naphth T)eth Tamine for Pt/alumina [108,231], derivatives of cinchona alkaloid such as 10,11-dihydrocinchonidine [36,71], 2-phenyl-9-deoxy-10, 11-dihydrocinchonidine [55], and O-methyl-cinchonidine for Pt/alumina [133], ephedrine for Pd/alumina [107], (-)-dihydroapovincaminic acid ethyl ester (-)-DHVIN for Pd/TiOz [122], (-)-dihydrovinpocetine for Pt/alumina [42], chiral amines such as 1 -(1 -naphtln I)-2-(I -pyrro 1 idiny 1) ethanol, l-(9-anthracenyl)-2-(l-pyrrolidinyl)ethanol, l-(9-triptycenyl)-2-(l-pyrrol idi nyl)cthanol, (Z )-2-(l-pyrrolidinyl)-l-(l-naphthyl)ethanol for Pt/alumina [37,116], D- and L-histidine and methyl esters of d- and L-tryptophan for Pt/alumina [35], morphine alkaloids [113],... 

This group of alkaloids has two structurally different a. The a of alkaloids found in the genus Cinchona (Ruhiaceae), such as quinine, quinidine, cinchonidine and cinchonine, is L-tryptophan. The j8 is tryptamine and the

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There are recognized at present three naturally occurring members of this group, cinchonamine, quinamine, and conquinamine, all minor alkaloids of certain Cinchona and Memijia species. The elucidation of their structures led to the suggestion that the quinoline moiety of the major bases, e.g., cinchonine and quinine, of these plants was probably derived from tryptophan via an indolic precursor. It has since been demonstrated from the results of feeding experiments with isotopically labeled tryptophan that this amino acid really can serve as a precursor of various indole alkaloids (1) as well as of quinine (2). The details of these processes are not yet known but probably involve an intermediate(s) related to cinchonamine (2, 3, 6). 

That the complex indole alkaloids contain a tryptamine unit is a requirement which is not always met at first sight. For example, some alkaloids from the Cinchona and Bemijia species (Rubiaeeae) (Volume VIII, Chapter 10 type Ij, Fig. 2) contain quinoline rings in their overall structures. Nevertheless, it has been shown that tryptophan is readily incorporated into these alkaloids and on this basis they are justly included in Table II. Furthermore, there are a number of complex alkaloids belonging to some Aspidosperma species (Apocynaceae) which seem to have lost the ethylamine side chain of a tryptamine unit (type li. Fig. 2). 

Feeding of tryptophan to Cinchona cell suspension cultures has been reported to result in considerable production of alkaloids 572,577,578). However, other authors reported that tryptophan inhibits the growth of the cell cultures and is converted, probably nonenzymatically, to norhar-mane and related compounds, and no increase in alkaloid production could be observed 586,587). 

The Quinoline Family. The amino acid tryptophan is the precursor of the quinoline alkaloids. Far less numerous than the isoquinoline alkaloids, the quinoline family is distinguished by having the famous dmg quinine as a member. Quinine has been used for ages in the treatment of malaria. It is isolated from the bark of the Cinchona tree. Quinine (3.20) has the rare stmctural feature of a bicyclic amine (a derivative of the l-azabicyclo[2.2.2]octane system) as a substituent. 

Biosynthesis In plants the quinoline system can be formed by several different biogenetic routes (biochemical convergence). In the Cinchona alkaloids tryptophan acts as the precursor while simple quinolines, furoquinolines, and acridines originate from an-thranilic acid. The second biosynthetic parmer is often a hemiterpene (for furoquinolines) or an iridoid monoterpene (secologanin, see secoiridoids) for Cinchona alkaloids. 

P.A.A. Harkes, P.J. de Jong, R. Wijnsma, R. Verpoorte and T. van der Leer, Influence of production media on Cinchona cell cultures spontaneous formation of B-carbolines from L-tryptophan, Plant Science, 47 (1986) 71-76. 

Among the alkaloids in this chapter derived from tryptophan, some do not retain the original nucleus of tryptophan, such as quinine, obtained from Cinchona plants (Rubiaceae), camptothecin, originally from Camptotheca acuminata (Cornaceae), and pyrrolnitrin of microbial origin. 

Quinine and related alkaloids isolated from the bark and other parts of Cinchona plants, such as Cinchona ledgeriana and Cinchona succimbra (Rubia-ceae), can be classified as quinoline alkaloids because these alkaloids also possess a quinoline moiety. However, the biosynthetic origin of the chro-mophore of these alkaloids is tryptophan rather than anthranilic acid. Namely, the quinoline moiety is formed by the oxidative transformation of the indole nucleus during biosynthesis, as described in Section 2.17. 

Quinoline alkaloids a group of alkaloids based on the quinoline skeleton. They are found both in microorganisms (see Viridicatine) and in higher plants. The most important therapeutically are the Cinchona alkaloids (see). The starting material for the biosynthesis of some Q. a. is anthranilic acid (see Viridicatine) for others it is tryptophan (see Cinchona alkaloids). 

Leetb [121] has employed TLC in an investigation of the incorporation of tryptophan into the cinchona alkaloids. 

Geerlings A, Hallard D, Caballero AM, Cardoso IL (1999) Alkaloid production by a Cinchona officinalis Ledgeriana hairy root culture containing constitutive expression constructs of tryptophan decarboxylase and strictosidine synthase cDNAs from Catharanthus roseus. Plant Cell Rep 19 191-196. doi 10.1007/s002990050732... 

Cinchona officinalis Catharanthus roseus Tryptophan decarboxylase (TDC), Strictosidine synthase (STR) Increased quinoline alkaloids in root culture... 

Bioconversion of Cinchona alkaloids is relatively less explored as compared to other natural products. The reason for this is the fact that none of the Cinchona alkaloid precursors are available at lower prices than the final alkaloids. The only exception is tryptophan however, it has no straightforward influence on the increasing production of alkaloids in cell cultures [267, 268]. 

The genus Cinchona (Rubiaceae) comprises about 25 species of tall, evergreen trees that grow in South America. The bark of these trees accumulates qumohue alkaloids that are, like camptotheciu, derived from tryptophan and secologaniu. Cinchona alkaloids are also found in the genus Remijia of the Rubiaceae family. 

There are recognized at present three naturally occurring members of this group, cinchonamine, quinamine and conquinamine (3-epiquinamine), minor alkaloids of certain cinchona species. Elucidation of their structures lead to the suggestion that the cinchona bases may be derived biosynthetically from Type I precursor and tryptophan. It has since been shown that isotopi-cally labelled tryptophan is incorporated into these quinoline bases. It is convenient to point out here some other alkaloids in which Type I precursor may be dissected out, e.g. the bisiso-quinoline base, emetine the indoleisoquinoline, tubulosine and also the indoles uleine and ellipticine which appear to have lost (or never had) the tryptophan side chain. (Chart 7.1)... 

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