Alkaloids norditerpenoid

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]. 

Gardner DR, Panter KE, Pfister JA, Knight AP. 1999. Analysis of toxic norditerpenoid alkaloids in Delphinium species by electrospray, atmospheric pressure chemical ionization, and sequential tandem mass spectrometry. J Agric Food Chem 47 5049. 

Steroidal Alkaloids and Steroidal Glycoalkaloids Norditerpenoid Alkaloids Pyrrolizidine Alkaloids Indolizidine and Polyhydroxy Alkaloids Tropane Alkaloids Glycosides... 

Over 40 norditerpenoid alkaloids have been reported in species of larkspurs. Data on toxicity in a mammalian system have been reported for 25 of these by the Poisonous Plant Research Laboratory (reviewed in Panter et ah, 2002). The commonality among all the wild larkspur species is the presence of norditerpenoid alkaloids, which are responsible for poisoning livestock. 

The MSAL-type alkaloids are potent neuromuscular poisons in mammals, acting at the post-synaptie neuromuseular junction. Variations in structural features of eaeh norditerpenoid alkaloid ean exaeerbate or reduee toxieity. While the mechanism of action of the norditerpenoid alkaloids involves blocking of neuromuscular transmission at the al nicotinic acetylcholine receptors, relative toxicity of individual alkaloids is observed to change with variations in the structural characteristics of the alkaloids (Dobelis et al., 1999). In comparison with the lyeoetonine and MDL-type alkaloids, the high toxicity... 

Figure 2.10 Norditerpenoid alkaloids from larkspurs (a) lyeoetonine (lyeoetonine type), (b) deltaline (MDL t5 pe), and (e) methyllyeaeonitine (MSAL type), with aeeompanying LD50.

Manners, G. D. and Pfister, J. A. 1993. Normal phase liquid-chromatographic analysis of toxic norditerpenoid alkaloids. Phytochemical Analysis, 4 14-18. 

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. ... 

Structural elucidation of norditerpenoid alkaloids is mostly straightforward since almost all the alkaloids fall in one major skeleton-type and have well defined substitution and configurational pattern. In addition 13C NMR data for norditerpenoid alkaloids is readily available to compare chemical shift data of alkaloids having closely related structures.6,7... 

Even though much is already known about the toxicity of diterpene alkaloids that contribute to the toxicity of Consolida, Delphinium, and Aconitium species, no antiviral study has been so far reported on this type of alkaloids. Therefore, no SAR studies have been encountered by us on the antiviral or antimicrobial activities of these alkaloids. However, a quantitative SAR analysis performed on a number of diterpene alkaloids isolated from an Aconitum sp. indicated that biological activity of these alkaloids may be related to their toxicity rather than to a specific pharmacological action [40]. In a current study on 43 norditerpenoid alkaloids from Consolida, Delphinium, and Aconitum species against several tumor cell lines, lycoctonine and browniine were... 

Geyerline (norditerpenoid alkaloid) Delphinium glaucum (larkspur) (Ranunculaceae) [root] nACh-R antagonist... 

When the norditerpenoid alkaloid imine 360 was subjection to reaction with MeI-NH40H and MCPBA, oxaziridine 361 was formed in 50% overall yield <2002H(57)2357>. Key steps in the proposed mechanism for the formation of 361 involve formation of a quaternary ammonium salt with Mel and peracid oxidation through a Baeyer-Villiger-type process. 

Shaheen et al. (2005) reported lycoctonine-type norditerpenoid alkaloids isolated from the aerial parts of Aconitum laeve Royle, swatinine, delphatine, lappaconitine, puberanine, and N-acetylsepaconitine [48]. They performed and reported the anti-inflammatory, antioxidant, and tyrosinase inhibition studies of all these compounds, in which lappaconitine (IC50 = 93.33 p,M) and puberanine (IC50 = 205.21 xM) were found to be active against the enzyme tyrosinase [48]. 

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. 

Maneerat W, Ritthiwigrom T, Cheenpracha S, Laphookhieo S. Carbazole alkaloids and coumarines from Clausena lansium roots. PkytochemLett 2012 5(l) 26-8. Manners GD, Panter KE, Ralphs MH, Pfister JA, Olsen JD, James LF. Toxicity and chemical phenology of norditerpenoid alkaloids in the tail Larkspurs Delphinium Species). J Agric Food Chem 1993 41 96-100. 

Usmanova SK, Aisa HA. Karaconitine, a new C-19-norditerpenoid alkaloid from Aconitum karakolicum roots. Chem Nat Comp 2011 47(2) 265—7. 

Pelletier, S. W., Studies in the chemistry of natural products Rearrangement reactions of diterpenoid and norditerpenoid alkaloids, J. Nat. Prod., 55, 1-24 (1992). 

Jing H, Yang XD, Zhao JF, Yang S, Zhang HB, Li L (2009) Ouvrardianines A and B, two new norditerpenoid alkaloids from Aconitum ouvrardianum. Helv Chim Acta 92 514-519... 

Joshi BS, Desai HK, Pelletier SW, Snyder JK, Jhang XL, Chen SY (1990) Tatsidine, a norditerpenoid alkaloid from Delphinium tatsienense. Phytochemistry 29 357-358... 

De Ines C, Reina M, Gavin J, Gonzales-Coloma A (2006) In vitro cytotoxicity of norditerpenoid alkaloids. Z Nat forsch 61 11-18... 

Shim SH, Kim JS, Kang SS (2003) Norditerpenoid alkaloids from processed tubers of Aconitum carmichaeli. Chcm Pharm Bull 51(8) 999-1002... 

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