Uncharacterized Alkaloids

In spite of the recent advances described in the foregoing text, there still remain a few old alkaloids whose structures have not yet been 

Lappaconitine has been found to occur in Aconitum septentrionale Koelle(i59), A. orientate 160), and A. excelsum Popov 161). Saponification of lappaconitine (C32H44NO8) gives lappaconine C23H37NO6) and acetylanthranilic acid. The molecular formula of lappaconine has been 

Talatisine and talatisamine were first isolated in 1940 along with isotalatizidine (CCCLIII) and talatizidine (CCCLIV) from the roots of 

Monoacetyltalatisamine has also been obtained with the previously 

The presence of a previously unreported alkaloid contaminating samples of deltaline from D. occidentale S. Wats, is briefly mentioned 31). The name given to this contamination is delphoccine. 

---

Newly Isolated Uncharacterized Alkaloids and Their Derivatives... 

Himalayas in India. The roots of this plant are known as Bish and were used by the native Indians for medicinal purposes. Later, this alkaloid was isolated from the roots of A. spictatum Stapf (39). Czechoslovakian (40) and Indian (41) workers reexamined the alkaloidal constituents of A. ferox and have reported the isolation of pseudaconitine along with other known and uncharacterized alkaloids. Recently, pseudaconitine was isolated (42) as a minor constituent of A. falconeri Stapf. The structure of pseudaconitine (20) was assigned earlier and is covered in detail in the last review (3) in this series. Because pseudaconitine has been chemically correlated with delphinine, the structure of this alkaloid must now be revised to 21. 

Delcorine (C26H4iN07 mp 200-202°) has been isolated (129) from the chloroform extracts of the aerial parts of D. corumbosum (D. corymbosum Regel) along with an uncharacterized alkaloid (mp 93-95°) and the known alkaloid methyllycaconitine (155). From chemical and spectral studies, delcorine was shown to have structure 167. 

Fig. 8.1 Sequence of reactions and pathways involved in the biosynthesis of indole alkaloids in Catharanthus roseus. The dotted lines indicate multiple and/or uncharacterized enzyme steps. Tryptophan decarboxylase (TDC), Geraniol Hydroxylase (GH), Deoxyloganin synthase (DS), Secologanin Synthase (SLS) Strictosidine synthase (STR1), Strictosidine glucosidase (SG), Tabersonine-16-hydroxylase (T16H), Tabersonine 6,7-eposidase (T6,7E), Desacetoxyvindoline-4-hydroxylase (D4H), Deacetyl-vindoline-4-O-acetyltransferase (DAT) and Minovincinine-19-O-acetyltransferase (MAT) represent some of the enzyme steps that have been characterized.

The versatility of strictosidine as a central intermediate for the biosynthesis of a variety of alkaloids is based on the highly reactive dialdehyde produced by the action of strictosidine p-D-glucosidase. This reactive intermediate is converted by uncharacterized enzymes into the major corynanthe, iboga, and aspidosperma skeletons that are elaborated into die several hundred alkaloids found in Catharanthns roseus. Since the biosynthesis of strictosidine appears to occur within plant vacuoles, there has been much speculation, but little is known, about the factors that regulate the accumulation of strictosidine within the vacuole, or which trigger its mobilization for further elaboration. It is well known that glycosides of different natural product classes are located within plant vacuoles. 

The early chemistry of the alkaloids of Alstonia species is characterized by confusion and colored by an acrimonious dispute between the two principal protagonists concerning the constituents of A. scholaris. Most of the bases isolated from this and other species were at best ill-defined and uncharacterized, and their identity and status as individual alkaloids are open to question it is probable that several of the substances obtained were simply the same alkaloid in different states of purity. 

Eurther, a compound collection based on the scaffold of the natural product Euranodictin (Eigure 9.12D) revealed a previously uncharacterized inhibitor class for the protein tyrosine phosphatases PTPIB and Shp-2." A compound collection which embodies the underlying scaffold structure of alkaloid cytisine and related natural products (Figure 9.12E) revealed the first inhibitor class of the vascular endothelial protein tyrosine phosphatase (VEPTP) at a hit rate of 1.57% as well as a completely new class of inhibitors for protein tyrosine phosphatase-IB and the phosphatase Shp-2. These two enzymes are targets for the treatment of the metabolic syndrome and diabetes as well as cancer respectively. In these cases the hit rates were ca. 0.3 to 0.4%. The screens revealed selective inhibitors for the proteins." ... 

Strictosidine is the general precursor of several divergent pathways leading to the multitude of TIAs accumulated by C. rosens. Somewhere, downstream of strictosidine formation, the pathway of TIAs suffers several ramifications mostly uncharacterized. The less ill characterized branches are the ones leading to catharanthine and vindoline, the monomeric precursors of the Vinca alkaloids, Fig. (2). Those branches will be the ones discussed here. 

The plant afforded a small amount of an uncharacterized third alkaloid. 

Cardiovascular agents - The metabolism of guinidine, a naturally occurring alkaloid with antiarrhythmic properties, was studied in man as the gluconate salt. Metabolites isolated from urine were found to be oxygenated on either the quinoline or guinuclidine portions of the molecule uncharacterized polyoxygenated derivatives were also found. Commercially available supplies of quinidine consistently contained 10 to 30 percent of an impurity. 

---