Alkaloids from tryptophan

Alkaloids from tryptophan can be classified into two groups. One of them is a small and simple group to which belong the calycanthus, canthinone, and )8-car-boline alkaloids the other is the monoterpenoid indole alkaloids. 

Without exception, monoterpenoid indole alkaloids appear only in the three families of Gentianales Apocynaceae, Loganiaceae, and Rubiaceae. Their biosyntheses have been studied for over thirty years, and a very important intermediate precursor has been found. Strictosidine, which is derived from the condensation of tryptamine and secologanin (Fig. 5.2.15), was shown to be the common precursor in the biosynthesis of the major classes of monoterpenoid indole alkaloids. 

Strictosidine was experimentally incorporated into a series of different alkaloids, including yohimbine-, strychnine- and gelsemine-type alkaloids (151). 

Furthermore, there are two alkaloid groups whose biosyntheses are closely related to those of monoterpenoid indole alkaloids namely, quinines and camp-tothecins. 

---

Bisindole Alkaloids from Tryptophan. There are two widely different types of alkaloids derived from two tryptophan (26) units. The first is a rather small group of compounds based simply on the dimers of tryptophan which includes compounds such as calycanthine (113) (Table 10),... 

Rebek, J., Jr., Tai, D.R, Shue, Y.K. (1984) Synthesis of Ergot Alkaloids from Tryptophan. Journal of the American Chemical Society, 106, 1813-1819. 

Alkaloids from tryptophan. The alkaloid harmine, which is found in several families of plants, can be formed from tryptophan and acetaldehyde (or pyruvate) in the same manner as is indicated for the formation of papaverine in Fig. 25-10. Some other characteristic plant metabolites such as psilocybine, an hallucinogenic material from the mushroom... 

The biosynthesis of terpenoid indole alkaloids from tryptophan has long been known.1,2 In new experiments with DL-[2-14C,2, 3 - 3C2]tryptophan [as (94)], this has been confirmed for vindoline (106).35 Incorporation measured by assay for radioactivity and by n.m.r. spectroscopy was the same, thus indicating an intact incorporation (with loss, of course, of the carboxy-group) (for discussion of the particular application of 13C labelling used here, see pp. 1-2). 

Just as terpenes could be viewed as being formed from isoprene units, alkaloids can be viewed as being derived from amino acids. Four amino acids give rise to important classes of alkaloids. As shown in Table 28.1, the pyrrolidine alkaloids are derived from the amino acid ornithine (not one of the 20 standard amino acids), the piperidine alkaloids from lysine, the isoquinoline alkaloids from tyrosine, and the indole alkaloids from tryptophan. 

In P. semperviva it has been demonstrated that tryptophan is a precursor of psilocybin (93a). It was simultaneously suggested that a similar oxidation of tryptophan or a tryptophan metabolite at the 4-position constitutes an important intermediate stage in the biosynthesis of the ergot alkaloids from tryptophan. 

The pattern of labelling is consistent with the formation of these alkaloids from tryptophan (with loss of the side-chain) and geranyl-geranlol pyrophosphate. Plausible cyclizations and rearrangements of the acyclic diterpene moiety afford the above structures). 

Fig. 6.1. Some relationships between primary and secondary metabolism. The probable origins are shown of the flavonoid, phenylpropanoid and isoprenoid group of compounds. The other groups discussed in the text, the non-protein amino acids and alkaloids, arise from a number of points in primary metabolism and only the origins of the tropane and pyrrolidine alkaloids from ornithine and proline and the indole alkaloids from tryptophan are shown.

Wiesler U-M, Weil T, Mullen K (2001) Nanosized Polyphenylene Dendrimers. 212 1-40 Williams RM, Stocking EM, Sanz-Cervera JF (2000) Biosynthesis of Prenylated Alkaloids Derived from Tryptophan. 209 97-173 Wirth T (2000) Introduction and General Aspects. 208 1-5 Wirth T (2003) Introduction and General Aspects. 224 1-4... 

Williams RM, Stocking EM, Sanz-Cervera JF (2000) Biosynthesis of Prenylated Alkaloids Derived from Tryptophan. 209 97-173... 

Indole alkaloids from Tabernaemontana plants are all biogenetically derived from tryptophan (tryptamine) and secologanine, which constitute the indole and terpenic portions, respectively, and can be classified into nine main types depending on the structural characteristics of their skeleton (Fig. 1). 

A few alkaloids, clearly originating from tryptophan and secologanine, cannot be accomodated in the previous types. They form the group of miscellaneous monomeric alkaloids. 

Scott and co-workers have also reported on the isolation of alkaloids from C. roseus cell suspension cultures 126). The cell line used, identified as CRW, afforded akuammicine (49), catharanthine (4), and strictosi-dine (33), and feeding experiments with labeled tryptophan led to incorporation into ajmalicine (39), akuammicine (49), catharanthine (4), and vindoline (3). The ability to produce alkaloids was carried through 8 successive generations. 

The precursors of true alkaloids and protoalkaloids are aminoacids (both their precursors and postcursors), while transamination reactions precede pseudoalkaloids (Tables 1 and 10). It is not difficult to see that from all aminoacids only a small part is known as alkaloid precursors (Table 19). Both true and proto alkaloids are synthesized mainly from the aromatic amino acids, phenylalanine, tyrosine (isoquinoline alkaloids) and tryptophan (indole alkaloids). Lysine is the... 

---