Alkaloids, Veratrum

Details of the total syntheses of verarine and 5a,6-dihydroveratramine have now been published. The latter compound had previously been converted into veratramine, jervine, veratrobasine, and 11 -deoxojervine, and so the present work completes a formal total synthesis of each of these natural products. 

Interest continues in the preparation of c-nor-D-homo-steroids from readily available Veratrum alkaloids. In this connection the jervine-derived enamine (14) gave the ketone (15) (40%) on sensitized photo-oxygenation. Similarly, enamine (16) gave the expected ketone (17) and the ring-contracted product (18).  

Preliminary communications of this work were reviewed by R. B. Herbert, in The Alkaloids , ed. J. E. Saxton, (Specialist Periodical Reports), The Chemical Society, London, 1973, Vol. 3, p. 292. 

Sasamori, and T. Masamune, Bull. Chem. Soc. Japan, 1976, 49, 499. 

A minor product of the photolysis of the hypoiodite derived from AT-acetyljervine (19) was originally assigned an oxetan structure (20). The structure of this product has been reassigned by the original authors and is now formulated as the acetal 

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In addition to the alkaloids such as cyclobuxiae-D (129) and solanidine (130) where the stmctural similarities to steroids are clear (although it must be remembered that detailed evidence actually linkiag the compounds is lacking) there are the less obvious (but nonetheless also clearly related) Veratrum alkaloids. These compounds, of which protoverattine A [143-57-7] (131), obtained from the rhizome of Veratrum album L. (LiUaceae), is a... 

The well-authenticated veratrum alkaloids are of three types —... 

Gaffield, W. (2000). The Veratrum alkaloids Natural tools for studying embryonic development, in Atta-ur-Rahman, Ed., Studies in natural products chemistry 23, Elsevier Science, Amsterdam, pp. 563-589. 

Gaffield, W., Incardona, J.P., Kapur, R.P. and Roelink, H. (2000). Mechanistic investigation of Veratrum alkaloid-induced mammalian teratogenesis, in Tu, A.T. and Gaffield W., Eds., Natural and selected synthetic toxins biological implications, American Chemical Society, Washington, pp. 173-187. 

Alkaloids are active bioagents in animal tissues. There is clear scientific evidence of this. Crawford and Kocan" " have tested the toxicity of steroidal alkaloids from the potato Solanum tuberosum), such as a-chaconine, a-solanine, solanidine and solasodine, and Veratrum alkaloid, jervine on fish. The results of Crawford and Kocan s research proved that rainbow trout exhibited a toxic response to chaconine, solasidine and solanine, while medaka only did so to chaconine and solanine. Embryo mortality was observed as an effect of toxicity in both species. Many other alkaloids are known to disturb or cause disorder in animal reproductive systems. For example, gossypol from cotton-seed oil is known as a clear reducer of spermatogenesis and premature abortion of the embryo. 

Wolters, B. 1970. Antimicrobial activity of Veratrum alkaloids. Planta Medica, 19 189-193. 

One method used for the control of hypertension is reduction of the impulses flowing from the CNS to the sympathetic nervous system which controls the tone of the cardiovascular system. The veratrum alkaloids do this at doses that are near the emetic dose, and reserpine acts both centrally and peripherally. The imidazoline clonidine (175) and some analogues in which the chlorine is replaced by fluorine or methyl groups decrease sympathetic outflow and cause vasomotor relaxation. However, they cause sedation, lack of saliva and renewed hypertension on withdrawal of the drug. 

Many of the alkaloids from Veratrum, Zygadenus and related genera are based on the cevane structure 1. The chemistry of the Veratrum alkaloids has been reviewed from time to time both in this treatise (1-3) and elsewhere (4-6). The most recent of these articles was published in 1973, and many new compounds have been discovered since then. Recent years have seen the announcement of many X-ray crystal structure determinations on these stereochemically complex alkaloids. A total synthesis has been reported for only one of the natural products, namely, verticine (7). The work that lead to this notable achievement has been reviewed (8). The pharmacology of both the alkaloids (9-12) and their synthetic derivatives (13) has been reviewed, although not since 1977. This chapter takes a different approach from previous reviews. The chemical reactions used for structure determination and modification are first summarized, but the main part of the chapter is a series of tables which include all the known cevane derivatives, both old and new. This is intended as a reference source for future workers in the field. The literature has been covered to the end of Volume 113 of Chemical Abstracts (1990). 

The application of traditional chemical methods to structure determination in Veratrum alkaloids is next illustrated by reference to selected examples. Some recent structural work, not previously reviewed, is included at the end of this section. 

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