Alkaloids gelsemium

14/9-hydroxy gelsedine R=H Ri=oh 14-hydroxygelsemicine R=OMe Ri=oh gelsenicine 20,N -dehydro humantendine 20,N -dehydro, Ri=oh 

---

Processes for the isolation and separation of the gelsemium alkaloids will be found in the papers cited and a number of methods of estimation, both chemical and biological, have been described, and standards suggested.il... 

Both Cushny and Dale found the amorphous gelsemium alkaloids represented by such fractions as gelseminine much more active than gelsemine. Cushny stated that gelseminine resembled coniine in action and showed a greater depressant effect on the central nervous system, but unlike coniine it exerted no pressor effect. It was also a powerful mydriatic. Dale found that 0-001 gm. of the hydrochlorides of the amorphous alkaloids injected into rabbits caused death from respiratory failure in 25 minutes, preceded by convulsions. These results are explained by the subsequent isolation from such amorphous fractions, of the potent alkaloids sempervirine and gelsemicine. 

Pharmacological studies and clinical applications of individual Gelsemium alkaloids or of the total alkaloids have never been reviewed before, so a preliminary treatment is presented in this chapter based on the limited data collected so far. For the convenience of identification, the names, molecular formulas, sources, as well as main references of all the Gelsemium alkaloids reported in the literature to date are listed in Table I. 

The humantenine-type Gelsemium alkaloids, which so far include human-tenine, humantenirine, and rankinidine, are oxindole alkaloids with a novel skeleton similar to that of gelsemine but lacking a bond between C-6 and C-20. From a biogenetic viewpoint, humantenine-type alkaloids are less evolved than those of the gelsemine series and might well be immediate precursors of them... 

Preliminary observation on 16 cancer patients who have been treated with the above-mentioned total alkaloid preparation indicates that symptoms are improved. Thus hepatic cancer patients have claimed disappearance of pain, improvement of appetite, and reduction of ascites patients suffering esophageal cancer claimed to have the self-feeling of relaxation of pain and disappearance of vomiting and upset stomach as well as the improvement of appetite. These preliminary results are quite encouraging, but certainly more extensive investigations are needed before the antitumor action of the Gelsemium alkaloids can be established. 

The order for the Gelsemium alkaloid preparation to be a practical remedy in the chemotherapy of cancers, caution must be paid to the safety problem. Thus, not only should the dosage itself be strictly controlled, but also further investigation of suitable methods of administration as well as the application of combination forms should be initiated. 

Baldwin, S. W., Doll, R. J. Synthesis of the 2-aza-7-oxatricyclo[4.3.2.04,8]undecane nucleus of some gelsemium alkaloids. Tetrahedron Lett. 1979, 3275-3278. 

In the first section, alkaloids isolated from the Gelsemium species up to now are presented in tabular form, and the structure elucidation of the representative alkaloids using mainly spectroscopic methods are described. The second part of this chapter covers the biogenetic speculation of the structurally unique Gelsemium alkaloids as well as the biomimetic transformation of the known indole alkaloids leading to the various skeletal types of Gelsemium alkaloids. 

Concerning a number of studies directed toward total synthesis of the Gelsemium alkaloids, only literature citations are given. 

---