Diterpenoid alkaloids Delphinium

Diterpenoid Alkaloids.—The Delphinium alkaloids have been reviewed in detail in the companion Specialist Periodical Report on Alkaloids. The structure of cuauchichicine, and in particular the stereochemistry at C-16, has been revised as a result of a correlation with (-)-/3-dihydrokaurane. The mechanism of the garryfoline-cuauchicine rearrangement has been examined by deuteriation studies. 

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). 

There is a long history of the use of Aconitum, Delphinium and Consolida species as the source of poisons and medicinals [1]. These three genera in Ranunculaceae family yield diterpenoid and norditerpenoid alkaloids. The name Delphinium derived from dolphine-delphine due to the shape of their flower buds [2]. Aconitum has an evil reputation from the antiquity [3]. The plant was used as poison in old Greece, also in north-west Pacific the natives used it to poison the whales and also as arrow poison. In England in the ancient times the plant was used against wolves, boars, tigers as well as against rodents, and it was also a homicide material [4]. 

Diterpenoid alkaloids have been isolated from the genera of the families Ranunculaceae (Aconitum, Consolida, Delphinium, Thalictrum), Garryaceae (Garraya), Rosaceae (Spiraea), and Compositae (Inula). These alkaloids can be divided into two broad categories norditerpenoid alkaloids (based on a C -skeleton) and the diterpenoid alkaloids (based on a Cft-skeleton).1 The chemistry of the diterpenoid alkaloids has been reviewed in earlier literature. ... 

Alkaloids of Delphinium dictyocarpum DC.—Dictysine [C21H33N03 m.pt 184—186°C] has been assigned structure (37) on the basis of chemical and spectroscopic studies.25" An unpublished X-ray analysis256 demonstrates that (37) is incorrect and that the structure should be as shown in (37a). Derivatives of dictysine (38)—(42) are shown here as the corrected structures. This alkaloid was isolated from the epigeal parts of Delphinium dictyocarpum DC.26 On acetylation of dictysine with acetyl chloride, the triacetate (38) and the two diacetates, (39) and (40), were obtained. The reaction of dictysine with one molar equivalent of periodic acid for three hours gave the a-hydroxy-ketone (41), while treatment with excess periodic acid for three days yielded the aldehyde carboxylic acid (42). These structures were supported by mass-spectral, i.r., and XH and 13C n.m.r. analyses. This is the first example of a C20 diterpenoid alkaloid which contains hydroxyl groups at C-16 and C-17. 

The diterpenoid alkaloids, isolated mainly from Aconitum and Delphinium species (Ranunculaceae), have been of great interest since the early 1800s because of their pharmacological properties. Extracts of Aconitum species were used in ancient times for treatment of gout, hypertension, neuralgia, rheumatism, and even toothache. Extracts have also been used as arrow poisons. Some Delphinium species are extremely toxic and constitute a serious threat to livestock in the western United States and Canada. Delphinium extracts also manifest insecticidal properties. In the last 30 to 40 years, interest in the diterpenoid alkaloids has increased because of the complex structures and interesting chemistry involved. 

Recently, a new class of diterpenoid alkaloids, known as bisditerpenoid alkaloids, has been isolated from the seeds of Delphinium staphisagria (2). The bisditerpenoid alkaloids (e.g., staphisine, iv) may be formally derived by... 

The genus Consolida, Aconitum, and Delphinium (Ranunculaceae) are well-known to be rich in diterpene alkaloids, which possess a diverse range of biological activities. These plants have also been the cause of poisonings, which primarily occur in cattle as well as human beings, due to toxicity of their alkaloids. In one of our recent studies, five diterpenoid-derivative alkaloids, lycoctonine (9), 18-O-methyllycoctonine (10), delcosine (11), 14-acetyldelcosine (12), and 14-acetylbrowniine (13) (as shown in Fig. 3) were screened for their antibacterial, antifungal, and antiviral activities [39]. 

Five new diterpenoid alkaloids have been isolated from Aconitum species (Ranunculaceae) and five from Delphinium species (Ranunculaceae). Four new Anopterus (Escalloniaceae) bases have been identified. The most significant synthetic achievement has been the total synthesis of racemic chasmanine. A detailed review of the alkaloids of Delphinium staphisagria has appeared.1... 

Revisions Based on 13C N.M.R. Analysis.—The revision of the structures of five C19 diterpenoid alkaloids on the basis of the 13C n.m.r. spectral data has been reported.8,9 Yunusov and co-workers,10 relying predominantly on mass-spectral data, had proposed structure (43) for acomonine (C2jH41N07), isolated from the roots of Aconitum monticola. Based partially on chemical correlations with acomonine, they later assigned structures to iliensine (44) (Cj NO,)11 and 14-dehydroiliensine (45),12 isolated from Delphinium biternatum. These were the first reported C19 diterpenoid alkaloids lacking an oxygen function at C-l. 

Alkaloids of Delphinium carolinianum Walt.—Delcaroline (C25N41N08 amorphous m.pt of perchlorate is 160—162 °C) was the major alkaloid isolated from whole plants of D. carolinianum Walt., which is native to the south-eastern United States.50 The known bases ajaconine (103) and browniine (7) were also isolated from these plants. Acetylation of delcaroline with acetic anhydride in pyridine gave the monoacetate (104). The structure (22) for delcaroline was assigned primarily on the basis of comparison of the 13C n.m.r. spectra of (22), its monoacetate (104), browniine (7), and dictyocarpine (8). Thus delcaroline, with a hydroxyl group at C-10 and a methoxymethylene group at C-4, represents a novel substitution pattern among the known C19 diterpenoid alkaloids. 

Delphinium species contain complex diterpenoid alkaloids that cause acute intoxication and death in cattle (6). The alkaloids and their concentrations vary with the species and plant part involved, which causes variability in toxicity. In Delphinium consolida (larkspur) there are toxic alkaloids in the non-medicinal plant parts (root, seed, herb), but they are purportedly absent in the medicinal part (the flower). 

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. ... 

Delectine.—A new diterpenoid alkaloid, delectine, has been isolated from Delphinium dictyocarpum7 This base, C31H44N2O8, m.p. 107—109 C, was shown to be the anthranilate ester (6) by chemical and spectral studies and by conversion into 00 -dimethyl-lycotonine (7). Acetylation of delectine gave an NO-diacetyl derivative (8). On alkaline hydrolysis of delectine, anthranilic acid and the alkamine (9) were obtained. Methylation of (9) with methyl iodide-sodium hydride gave (7), which was... 

Diterpenoid Alkaloids.— The alkaloids of Delphinium staphisagria include some bisditerpenoid alkaloids such as staphidine, staphinine, and staphimine. The full paper has appeared on the structure and stereochemistry of delphisine, neoline, chasmanine, and homochasmanine. The application of n.m.r. measurements to these alkaloids has led to the revision of the structure of the alkaloid A from D. bicolor... 

Waller and co-workers have used g.l.c.-mass spectrum combination in studies of diterpenoid alkaloid synthesis in Delphinium plants. 

Condelphine from Delphinium confusum and D. denudatum has been assigned19 structure (26) on the basis of chemical and spectral evidence. The configuration of the C(15)-methoxy-group was unassigned and the absolute configuration of the molecule was assumed by analogy with that of other diterpenoid alkaloids. 

Diterpenoid alkaloids from Delphinium cardiopetalum (Ranunculaceae)... 

Similarly it has been shown that the most potent norditerpenoid alkaloids acting as inhibitors of mammalian and insect cholinergic receptors have the C-l 8 anthranilic acid esterification, characteristic of the Delphinium norditerpenoid alkaloid methyllycaconitine (MLA), structurally-related to aconitine [40-42], MLA also had antifeedant effects against Spodoptera eridania with associated post-ingestive and toxic effects at doses within the effective antifeedant dose range of compound 30 [40], suggesting a similar antifeedant mode of action between MLA/aconitine and the C-20 diterpenoid alkaloids. 

The Diterpenoid Alkaloids from Aconitum, Delphinium, and Garrya... 

During the past year the diterpenoid alkaloids have attracted more interest than in previous years. Reports have appeared on the alkaloids of Aconitum and Delphinium species found in Bulgaria, Canada, Japan, Norway, Spain, the Peoples Republic of China, several regions of the Soviet Union, and the southeastern and western United States. 

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