Atisine-type alkaloids

E. Intermediates for the Veatchine and Atisine-Type Alkaloids 1. A New Method for Construction of Ring A... 

To establish the generality of this procedure, the Australian chemists synthesized (179) the enedione 376 from 375 as shown in Scheme 2. Compound 376 contains the BCD ring system of the atisine-type alkaloids. 

The acid-catalyzed rearrangement of 377 and 379 afforded 378 and 380, respectively, in good yields. The tricyclic ketone 380 contains all appropriate functionality for the synthesis of the atisine-type alkaloids, ajaconine and atidine. 

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... 

C, Synthesis.—Atisine and Veatchine Types. Zalkow and co-workers developed syntheses of intermediates potentially transformable into atisine-type alkaloids, starting with podocarpic acid. The general approach is illustrated by a synthesis" of an ajaconine degradation product. Methyl O-methyl-7-keto-podocarpate (56) was reduced to the diol, which was converted by Birch reduction to dienone (57). The diene diol diacetate from this was converted to the 7,8-epoxide. Boron trifluoride converted this to the non-conjugated enone (58) which isomerised and... 

The second approach to (50) was more direct. Acetylation of (51) was followed by sequential treatment with oxalyl chloride and excess diazomethane to afford, after hydrolysis, the diazoketone (53). Boron trifluoride etherate in nitromethane proved to be the best system to catalyse the cyclization of (53) to (50). This route may provide a useful intermediate for syntheses of atisine-type alkaloids. 

Miyaconitine and Miyaconitinone.—A brief report of further chemical studies of miyaconitine (41) and miyaconitinone (42) has been published. These modified atisine-type alkaloids were isolated from Aconitum miyabei Nakai. ... 

Ayer and Despande (155) have reported the rearrangement of tosylate 313 into diene 319 by solvolysis or even by passage of a benzene solution through silica gel. This rearrangement serves as a model for the proposed (152) biosynthetic transformation of the atisine-type alkaloids to the aconitine-type alkaloids. 

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. ... 

The overall transformation of the atisane skeleton e.g. atiserene, 274) to the Ci9 aconite alkaloids, apart from oxidative and functionalization steps, requires three principal structural alterations C7-C20 bond connection, removal of one carbon (C17), and rearrangement of the Cg-Cg bond to C15. Although the order of these alterations is not known, the isolation of the atisine-type alkaloid, denudatin (285), which possesses the C7-C20 link, indicates that this step may occur first. 

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. 

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. 

Denudatine (C21H 3 3NO2). Delphinium denudatum was the source of this alkaloid. The presence of an atisine-type skeleton was inferred from the presence of an allyl alcohol system which rearranged in the presence of palladium on charcoal to a methyl ketone with 1710 cm" The location of a hydroxy-group on... 

Hypognavinol and anhydroignavinol join the recently reported miyaconitine8 as alkaloids of the modified atisine type bearing a hydroxy-group at C(9). 

In 1973 Wiesner and his colleagues reported (161) a new synthetic route for the construction of the substituted C/D ring system of delphinine-type alkaloids. This process was based on a previous photochemical synthesis of the atisine skeleton (162). 

The Total Synthesis of Talatisamine.—The atisine-type intermediate (62) has been used in the synthesis of talatisamine (63).A key step in this synthetic route is the rearrangement of an atisine skeleton (structure B) to a lycoctonine skeleton (structure A). This type of rearrangement has been proposed in the biogenesis of alkaloids possessing the lycoctonine skeleton. Johnson and Overton S and Ayer and Deshpande have previously reported studies of this process. 

Chemical Conversions of Kobusine.—Okamoto and co-workers have reported some of their recent studies of the chemistry of kobusine (74), a C-14-C-20-bridged atisine-type diterpenoid alkaloid. Since this bond constitutes a bicyclo-[3.2.1]octane system, and conversion into a double bond would violate Bredt s rule, there would appear to be no simple way to cleave it, Kobusine was reduced to (75) with sodium in n-propanol to protect the allylic alcohol. Acetylation 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). 

Table 28.2 Diterpenoid alkaloids (compound 1-2 ranaconitine-type Cig-diterpenoid alkaloids, 3-13 aconitine-type Cig-diterpenoid alkaloids, 14—24 lycoctonine-type Cig-diterpenoid alkaloids, 25 Cig-rearranged-type Cig-diterpenoid alkaloid, 26-27 atisine-type C2o-diterpenoid alkaloids, 28 hetidine-type C2o-diterpenoid alkaloid, 29-36 hetidine-type C2o-diterpenoid alkaloids, 37-41 denudatine-type C2o-diterpenoid alkaloids, 42-51 vakognavine-type C2o-diterpenoid alkaloids, 52 atisine-denudatine-type C2o-diterpenoid alkaloid)...

This type of alkaloids is similar to the atisine type except of an additional bond between C-20 and C-7. Five new compounds, two of them, namely, anthriscifolmines A (55) and B (56) from D. anthriscifolium [41] and liangshantines A-C (57-59) from A. liangshanicum [36], have been isolated from 2009 to Feb. 2012. Compound 56 is a rare C2o-diterpenoid alkaloid bearing a CH2OH-I8 moiety attached to C-4. 

The aconitine-type alkaloid (96) is most probably formed from the atisine skeleton through different modifications as indicated in Scheme 28.4. The intermediate 94 after a Wagner-Meerwein rearrangement process converts two fused six-membered rings into a (7 -i- 5)-membered bicyclic system in which C-17 exocyclic... 

The alkaloids of the genus Delphinium may be classified into two distinct structural types the atisine type, represented by ajaconine, and the lycoctonine type, represented by delcosine, acetyldelcosine, and delsoline (Figure 3.18). The common larkspurs are widely distributed in the western United States and in Canada where they are a common cause of cattle poisoning. Both types of alkaloids from Delphinium ajacis have been studied (Frost et al., 1967). Plants were grown in the field on sandy loam soil at the Horticultural Farm in Stillwater with normal fertilization and... 

Wiesner, K., T. Y. R. Tsai, K. Huber, S. E. Bolton, and R. Vlahov Total Synthesis of Talatisamine, a Delphinine Type Alkaloid. J. Amer. Chem. Soc. 96, 4990 (1974). PRZYBYLSKA, M., T. Y. R. TsAi, and K. Wiesner Conversion of the Alkaloid Atisine into a Compound with the Lycoctonine Skeleton. Chem. Commun. 1975, 297. 

The stereochemistry of the normal-type oxazolidine ring in veatchine, atisine, and other related alkaloids was ill-defined in the literature (25),... 

Staphisagnine (193) and staphisagrine (194) were also isolated (150) in extremely small amounts from the mother liquors accumulated during the isolation of delphinine from the seeds of D. staphisagria. These alkaloids are unusual in containing an oxazolidine ring of the atisine and veat-chine type in addition to many of the uncommon features of the staphisine skeleton. 

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