Alkaloids from Phenylalanine and Tyrosine
Several groups of relatively unrelated alkaloids include portions of the molecule derived from
phenylalanine and other portions derived from tyrosine.
Colchicine and related alkaloids
Colchicine is found in the leaves and seeds of at least 19 species of Colchicum and 10 other related genera. These plants have traditionally been placed in the family Liliaceae. Others have segregated them into a family Colchicaceae. The amide nitrogen of colchicine is not basic; some have argued that this compound is not a true alkaloid. About 30 other tropolonic alkaloids are known to occur.
The biosynthesis of colchicine involves both tyrosine and phenylalanine. The isolation and characterization of androcymbine, as well as its recognition as an intermediate in the pathway was a major step in understanding the biosynthesis of colchicine. The tropolone ring is generated by a ring expansion step.
Colchine interferes with microtubule functions and binds to tubulin. Treated cells are arrested at metaphase. The transport of vesicles also is affected.
Colchicine is used to treat gout. The drug is efficacious, but also quite toxic. This compound also has antitumor activity, but is too toxic for practical use.
Colchicine is used to introduce polyploidy in plants. This leads to a doubline of chromosome number
and has been useful in plant genetic studies as well as for production of new plant cultivars.
Amaryllidaceae alkaloids
Norbelladine, an adduct of phenylalanine and tyrosine, is a key intermediate in the formation of alkaloids of this group. Three major structural types are generally recognized; they are formed by cyclization and subesequent modification of metylated derivatives of the norbelladine precursor in different ways.
One series of Amaryllidaceae alkaloids includes compounds such as lycorine, norpluviine, lycorenine, and homllycorine. These occur in daffodil or jonquil cultivars, as well as in related plants.
A second major structural type leads to the formation of haemanthamine and involves a para-para instead of an ortho-ortho coupling. Other alkaloids of this series are pretazettine, and tazetine.
The third series of Amaryllidaceae alkaloids leads to narwedine, galanthamine, and related alkaloids.
A number of these alkaloids have proven medically useful, but most are too toxic for practical use.
Galanthamine has potent cholinergic activity and analgesic activity about same as morphine. It also inhibits acetylcholine esterase.
Lycorine, narciclasine, and pretazettine are of interest as antitumor compounds. Lycorine inhibits
ascorbic acid synthesis, as well as cell division and cell elongation. This compound also inhibits
DNA polymerase, protein synthesis, and herpes simplex virus. Narciclasine halts protein synthesis
by blockage of peptide-bond formation on the 60-S ribosomal unit. Many of these alkaloids have antiviral
activity.
Mesembryanthemum alkaloids
A unique series of alkaloids are found in the genera Mesembryanthemum and Scletium,
Mesembryanthemaceae. About 25 alkaloids of this type are known. Some are hallucinogenic. They were
used by the Hottentots and Bushmen of the South-West Cape Province for preparation of a drug called
"channa".
Cephalotaxus and homoerythrina alkaloids
Cephalotaxus (Cephalotaxaceae) alkaloids have antitumor activity. These Asian plants are cultivated in a number of countries. About 20 compounds are found onley in this genus. Another 10 are homoerythrina alkaloids. The latter group of alkaloids are sometimes found in other plants.
Biosynthetic studies indicate that one portion of the structure is derived from phenylalanine and the other from tyrosine. Cephalotaxine occurs esterified to a series of somewhat unusual hindered acids. The acids appear to be derived from L-lysine. The homoerythrina alkaloids in this plant also are synthesized from phenylalanine and tyrosine.
Only the four esters harringtonine, homoharringtonine, isoharringtonine, and deoxyharringtonine have significant antitumor activity. They inhibit DNA synthesis and protein synthesis.
Lecture Slides
Plants with Alkaloids Derived from
Both Phenylalanine and Tyrosine
© David S. Seigler, Plant Biology 363, Plant Secondary Metabolism, Department of Plant Biology,
265 Morrill Hall, 505 S. Goodwin Ave., University of Illinois, Urbana, Illinois 61801, USA.
217-333-7577. seigler@life.uiuc.edu.
