Diterpenoid type alkaloids

Table 2 Tyrosinase inhibitory activities of the diterpenoid and napelline type alkaloids and their derivatives [49]...

The chemistry of the diterpenoid alkaloids, rather than their structure elucidation by physical methods, has attracted more interest during the year covered by this Report. While several new alkaloids have been reported, most of the research on these polycyclic, polyfunctional bases has involved chemical conversions and synthetic methods. Most notably, Wiesner s group at New Brunswick, Canada, has reported a fourth-generation synthesis of the delphinine-type alkaloids. That this marvel of synthetic engineering accomplishes the stated goals1 of a highly efficient, fully regio- and stereo-specific synthesis of these complex natural products is abundantly clear. 

The 13C-NMR spectra of these compounds were analyzed to identify and distinguish skeletal features of the atisine and veatchine-type alkaloids for use in the structure elucidation of new C20-diterpenoid alkaloids. 

Alkaloids of Aconitum falconeri Falaconitine and Mithaconitine. In addition to the previously known veratroylpseudaconine (5), pseudaconitine (6) and indaconi-tine (7), two new C19 diterpenoid alkaloids, falaconitine and mithaconitine, have been isolated from the roots of Aconitum falconeri Stapf.13,14 Singh and coworkers15 had reported a preliminary study of the two alkaloids, bishatisine and bishaconitine , isolated from this species. However, in the recent work,13,14 no bishatisine or any atisine-type alkaloid was identified, and the data reported for bishaconitine were consistent with a mixture of falaconitine and several closely related bases. The identities of (5), (6), and (7) were determined primarily by H and 13C n.m.r. techniques and confirmed by comparison with authentic samples.14... 

Structure Revisions and General Studies Revision of the Structures of Thirty-seven Lycoctonine-related Diterpenoid Alkaloids.—Lycoctonine was assigned structure (1) on the basis of an X-ray crystallographic analysis of (2) in 1956.4 Since that time, the structures of most of the lycoctonine-type alkaloids have been based on correlations with lycoctonine. 

Research on diterpenoid alkaloids published during the past year has continued to expand the body of structural and synthetic information available on these complex plant bases. The structures of ten new alkaloids from Aconitum and Delphinium species, including seven new bisditerpenoid alkaloids, have been reported. Tlie most significant progress in methods of structure elucidation has been the very successful applications of n.m.r. to the study of complex diterpenoid alkaloids. The New Bruns wick group under Professor Karel Wiesner has continued its progress toward the syntheses of the Ci9-aconitine-type alkaloids. An historical account of the synthesis of talatisamine (1), the first synthesis of a hexacyclic aconite alkaloid, has been published. This work was reviewed in a previous Report. ... 

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 ... 

Veatchine- and Atisine-type Alkaloids.—Novel Syntheses of the Diterpenoid BCD Ring System. The preparation of the BCD ring skeleton of the atisine (36) and veatchine (63) alkaloids by an intramolecular carbenoid addition has been reported by Beames, Halleday, and Mander. ... 

Reactions of Some Aconitine-type Alkaloids.—Ichinohe et al have reported a study of some reactions of C,9 diterpenoid alkaloids. They attempted to correlate... 

Applications of N.M.R. Spectrometry to the C19 Diterpenoid Alkaloids 14-Acetylbrowniine.—A review of recent applications of carbon-13 n.m.r. spectrometry to the solution of some of the complex problems of C19 diterpenoid alkaloid chemistry has appeared. Using proton-decoupling techniques and additivity relationships, the carbon-13 chemical shifts for eighteen aconitine and lycoctonine-type alkaloids were assigned. Applications of these methods for the identification and structure elucidation of several new diterpenoid alkaloids were discussed. The new data presented in this work included the identification of... 

Epimerization and Isomerization of the Oxazolidine Ring System in the C20 Diterpenoid Alkaloids A -Ray and N.M.R. Studies.—The nature of the oxazolidine ring system in the atisine- and veatchine-type alkaloids has received considerable attention during the past year. (c/. this Report, 1978, Vol. 8, p. 238). 

Numerous UCNMR investigations on alkaloids have been reported in the literature [598, 599]. In Table 5.13 the 13C chemical shifts and structures of representative alkaloids of different types are collected Pyrrolidine, piperidine and pyridine [600-602], tropane [600, 603-605], izidine [606-612], indole [600, 603, 613-633], isoquinoline [599, 630, 634-647], quinolinic [648-656], imidazole [657], yuzurimine alkaloids [658], alkaloids with exocyclic nitrogen [659, 660], diterpenoid [661-663], steroid [664-666] and peptide alkaloids [667-671], The complete signal assignment for the alkaloids given in Table 5.13 was achieved using the correlations between 13C NMR spectral parameters and structural properties and the 13C chemical shift values of model compounds described in Chapters 3 and 4 of this monograph. 

The naturally occurring diterpenoid alkaloid miyaconitinone (Al-type) contains a diketone at the C(6), C(7) positions and caidionidine (Al-type) possesses an anhydride group in the B-ring between C(6), C(7). In albovionitine (Al-type), the C(18) methyl... 

Diterpenoid Alkaloid Natural Occurrence (N) Derivative (D) Structure Type X-Ray H c... 

Vakognavine is the first example of an N, C-19-seco-diterpenoid alkaloid reported and an interesting alkaloid for biogenetic speculation. The authors (116) suggested that the C-19 aldehyde may be a plausible alternate to the pseudokobusine structure as an intermediate in the biosynthesis of the modified atisine-type skeletons such as hetisine. The C-19 hydroxyl of vakognavine hydriodide (119) is reminiscent of the oxazolidine oxygen of isoatisine. 

A new approach to the abe ring system of the pentacyclic C20 diterpenoid alkaloids has been reported by van der Baan and Bickelhaupt.51 For the model system of major interest, (134) was prepared from (133) by reaction with cyano-acetamide. Treatment of (134) with allyl bromide gave almost exclusively C-alkylation, to afford (135). On heating (135) at 100—110°C, a Cope-type rearrangement to (136) was effected. This compound was then N-alkylated with ethyl iodide-DMF, the product being (137). Treatment of (137) with IV-bromosucc-... 

While skeletal muscle ryanodine receptors are involved in excitation — contraction coupling through direct interactions with voltage-gated Ca2+ channels, in other cell types ryanodine receptor Ca2+ channels located on the ER membrane are opened by cADPR in a Ca2+-CaM-dependent fashion. Ca2+ and plant metabolites such as the diterpenoid alkaloid ryanodine and the methylxanthine caffeine promote opening of the ryanodine receptor Ca2+ channel. Ryanodine can also negatively modulate the receptor (Table 4.4). 

Acylation and Hydrolysis Studies.— The relative reactivities of the C-1 and C-14 oxygen functionalities in a series of lycoctonine-type diterpenoid alkaloids have been examined. Diacetyl-talatizamine (63) and triacetyl-lappaconine (64), which contain C-1 methoxyl functions, were saponified approximately three times faster than diacetyl-karakoline (12), diacetyl-talatizidine (65), and tetra-acetyl-lappaconidine (66), all of which contain C-1 acetoxy-groups. In addition, karakoline (11) and karakolidine (10) were selectively mono-acylated at C-1. From these limited data the... 

Taxane alkaloids are made up of a terpenoid core and a phenylpropanoid (3-amino acid, joined by an ester bond. They can be classified according to the carbon-carbon connectivity of the terpenoid core and the type of the side-chain. Thus, the diterpenoid core can be of the taxane- (Tables 3-8), 11 (151 )abeotaxane-(Table 10), 2(3->20)abeotaxane-(Table 2) or 3-11-cyclotaxane (Table 9) type, whereas the side chain can be Winterstein s add [L(R) (3-dimethylamino-P-phenylpropionic add] or N, A/-dimethylphenylisoserine (2R, 3S (threo) a-hydroxy-3-dimethylamino-P-phenylpropionic acid). Further modification occurs in the... 

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). 

The effect on the u.v. and i.r. spectra due to trans-spatial carbonyl interactions was first noted in the diterpenoid alkaloids in 1954. Comparable observations in the chemistry of delpheline ° were followed by a study of carbonyl-olefin interactions." Subsequently, a number of cases of the last type of interaction were recognised in diterpenoid alkaloids. Delnudine (8) has a /3y-unsaturated carbonyl system, and the nn band is shifted to 300 nm, with a moderately enhanced log e of 1.76. The X-ray analysis showed the carbonyl carbon and nuclear double bond carbon to be 2.90 A apart, with the plane of the two double bonds inclined at 34°. 

The genus Anopterus, which also has two species found in Tasmania and in New South Wales, respectively, belongs to the family Grossulariaeeae and was likewise not known to elaborate alkaloids before a study by CSIRO workers. They found that both species produce a series of diterpenoid alkaloids with a new type of ring system, of which anopterine (19) 39 provides an example. The structure comprises several fused rings, and when the ester groups are hydrolysed and the resultant diol is oxidised, the nucleus becomes even more convoluted and forms the extraordinary cage structure 20 40. ... 

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