Ci9-diterpenoid alkaloids

The genera of Aconitum (commonly known as Monkshood) and Delphinium, and to a lesser extent Rumex, Consolida, and Spiraea, have long been recognized as a rich source of alkaloid natural products [1], The diterpenoid alkaloids are generally classified into two major groups the Ci9-diterpenoid alkaloids (sometimes referred to as the Cig-norditerpenoid alkaloids) and the C2o-diterpenoid alkaloids. Within the C2o-diterpenoid alkaloids, at least 11 separate classes have been isolated, including the hetisine alkaloids (Chart 1.1). 

This technique is of paramount importance in structural studies in this area, and is used extensively. The chief types are proton and carbon-13 nmr spectroscopy, which will be dealt with separately. A lengthy review chapter on the application of nmr-spectroscopy to Ci9-diterpenoid alkaloids is noteworthy (Pelletier et al., op. ait.-, see also idem, in "The Alkaloids. Chemistry and Physiology," ed. R. H. F. Manske and R. G. A. Rodrigo, Vol. XVII, Chapter 1, Academic Press, New York, 1979). 

IV. Alkaline Hydrolysis and Acetylation Studies of Ci9-Diterpenoid Alkaloids 54... 

These diterpenoid alkaloids may be divided into two broad groups those based on a hexacyclic Cjp-skeleton, and those based on a C20-skeleton. The Ci9-alkaloids are commonly called aconitines, and all possess either the aconitine, the lycoctonine, or the heteratisine skeleton. Usually in the literature, the Ci9-diterpenoid alkaloids are referred to as either aconitine-type or lycoctonine-type alkaloids without structural differentiation. Because this practice sometimes creates confusion, we have divided the Ci9-diterpenoid alkaloids into three categories, defined as follows ... 

The earlier work on the chemistry of Ci9-diterpenoid alkaloids has been reviewed in Volumes IV (1), VII (2), and XII (3) of this series, in books on alkaloids by Boit (4) and Pelletier (5), in The Alkaloids, Specialist Periodical Reports, (6-8), and in other reviews (9, 10). This chapter deals with the recent developments in Ci9-diterpenoid alkaloid chemistry reported in the literature available to us since July 1968, as well as certain unpublished work from our laboratory. 

Because previously published books (11,12) in the field of natural products have reported structures now known to be incorrect of several well-known Ci9-diterpenoid alkaloids, we have included in this chapter a catalog of all the known C 19-diterpenoid alkaloids, showing the correct structures, physical properties, plant sources, and key references. This catalog should be very useful, for it presents in a single place important structural information on the Ci9-diterpenoid alkaloids, which has been scattered through hundreds of papers and dozens of reviews. 

Biogenetically, it is interesting to observe that the delphirine-neoline pair is the second example reported so far of C-l hydroxyl epimers among the Ci9-diterpenoid alkaloids. The isotalatizidine (61)-talatizidine (62) pair 84, 85) is the first example in this series. 

The Canadian workers, Jones and Benn, reported the isolation of two new diterpenoid alkaloids A and in very small amounts from >. bicolor Nutt (100,101). Structures 83 and 84 were assigned to alkaloids A and B, respectively, primarily on the basis of the correlation with the 13C NMR spectra of a variety of model Ci9-diterpenoid alkaloids, e.g.-, deoxyly-coctonine and isotalatizidine, and the results obtained from the pyrolysis study of alkaloid A. Alkaloid A (C25H39NO6), an amorphous base, formed a hydroiodide salt (mp>240°). The IR and H and 13CNMR spectra revealed the presence of a tertiary methyl, an N-ethyl, an acetoxyl, two... 

Lappaconitine represents the first example of a Ci9-diterpenoid alkaloid with one of the carbon atoms, which is usually attached to C-4, replaced by an oxygen atom. The presence of the C-8-C-9 vicinal diol system in lappaconitine is also unusual. 

The tubers of A. karakolicum collected from the Terskei Ala-Tan ranges of the Kirghiz S.S.R. yielded a new alkaloid (16) designated as aconifine (C34H47NO12 mp 195-196°). Along with this new alkaloid, the tubers of A. karakolicum also afforded the well-known Ci9-diterpenoid alkaloid aconitine (4) and the two known -diterpenoid alkaloids, songorine and napelline. 

In 1972, Jones and Benn (100, 101) made a significant contribution in the application of 13CNMR spectroscopy by demonstrating the use of 13C NMR studies in elucidating the structures of two new Ci9-diterpenoid alkaloids. The 13C NMR spectra of the several aconitine- and lycoctonine-... 

The mass spectra of Ci9-diterpenoid alkaloids are complex, and there is a paucity of information concerning their fragmentation patterns. The first application of mass spectral data to the structure elucidation of complicated Ci9-diterpenoid alkaloids involved a study of heteratisine and related alkaloids (142). On the basis of the mass spectral analysis of heteratisine... 

Chapter 1. The Structure and Synthesis of Ci9-Diterpenoid Alkaloids S. William Pelletier and Naresh V. Mody... 

The Ci9-diterpenoid alkaloids are the largest class of naturally occurring diterpenoid alkaloids with more than 700 compounds so far isolated and characterized from around 315 species of plants mainly from the generz. Aconitum and Delphinium. This class of alkaloids is divided into six types aconitine type (B-1), lycoctonine type (B-2), pyro type (B-3), lactone type (B-4), l, l-seco type (B-5), and rearranged type (B-6) (Fig. 28.2). The order of types from B-1 to B-6 is based upon the higher to lower number of alkaloids obtained so far. In between 2009 and Feb. 2012, only aconitine, lycoctonine, and rearranged-type Cig-diterpenoid alkaloids have been isolated and are discussed herein. 

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