C2o 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). 

Surveys of recent developments in the chemistry of C2o diterpenoid alkaloids,4 of the alkaloids of Consolida ambigua,5 and of the synthesis of diterpenoid alkaloids by thermolysis6 have appeared. 

Conversions of the Oxazolidine Rings in C2o Diterpenoid Alkaloids.—Several studies of the formation and opening of the oxazolidine ring system in the C20 diterpenoid alkaloids have been reported.33-35... 

Ghatak and co-workers52 have reported an interesting approach to the preparation of key intermediates in the syntheses of C2o diterpenoid alkaloids and C2o... 

Synthesis of Hesitine Diterpenoid Alkaloids. An efficient enantioselec-tive approach to the hesitine class of the C2o-diterpenoid alkaloids involves an intramolecular oxidopyridinium dipolar cycloaddition with a vinylic sulfone as the key transformation as depicted in Eq. 156.266 Once the sulfonyl group has played its role in the C-C bond formation, it is removed by a Na/Hg-promoted reductive desulfonylafion. 

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 comparatively simpler Cao-diterpenoid alkaloids bears a pentacyclic core in the structure. Only two new compounds named delphatisine C (44) from D. chrysotrichum [42] and honatisine (45) from D. honanense [43] have been isolated between the periods of 2009 and Feb. 2012. Compound 44 contains a five-membered lactone ring connecting to the oxazolidine ring. Extensive NOESY experiments were required to elucidate the relative configuration. Compound 45 is a novel C2o-diterpenoid alkaloid containing an unique l, 3, 5 -trimethyl-4 -oxocyclohexyloxy unit attached to C-24. 

This type of alkaloids has a hexacycUc core with an additional bond at C-20-C-14. They are more complex than the atisine alkaloids. One new hetidine-type C2o-diterpenoid alkaloid named anthriscifolmine I (46) was reported between 2009 and Feb. 2012 from D. anthriscifolium [44]. 

This type is one of the most complex groups derived from the atisine skeleton having a heptacyclic system with an additional N-C-6 bond. A total of eight hetisine-type C2o-diterpenoid alkaloids (47-54) were isolated in the period of 2009 to Feb. 2012 [16, 41, 44 46]. Besides the complexity of the skeleton, acetyl, benzoyl, tertiary methyl, hydroxyl, O-formyl groups as well as an exocyclic double bond and a ketone make this skeleton a unique structure. 

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. 

This type of alkaloid have an N,l9-seco hetisine skeleton in addition to a C-4 aldehyde moiety. This type is named after the first compound vakognavine [64,65]. Ten new vakognavine C2o-diterpenoid alkaloids have been isolated between 2009... 

In the year 2010, a novel C2o-diterpenoid alkaloid named piepunine (70) has been isolated from A. piepunense containing both atisine and denudatine skeletons [48]. Compound 70 represents the first example of this type. 

This paper described the chemotaxonomy characteristics of two C2o-diterpenoid alkaloids and five C 19-diterpenoid alkaloids from Delphinium albocoeruleum Maxim of Chinese origin. The study indicated that the compound delelatine may be considered as a chemotaxonomic marker for the Delphinium genus as it occurs in Delphinium elatum. Delphinium barbeyi, D. tatsinenense [66], and Delphinium giraldii [67], Delphinine, a major compound, may possibly be utihzed for identification of D. albocoeruleum Maxim. 

Liu XY, Song L, Chen QH, Wang FP (2010) Two new C2o-diterpenoid alkaloids from Delphinium anthriscifolium var. savatieri. Nat Prod Commun 5 1005-1008... 

C2o-diterpenoid alkaloids are classified into four groups according to Wang et al. [19] ... 

The less-toxic groups of C19- and C2o-diterpenoid alkaloids have been reported to possess no analgesic activity [31, 33]. 

Gonzalez et al. have reported that three molecules of the C2o-diterpenoid alkaloid group 15,22-0-diacetyl-19-oxo-dihydroatisine, azitine, and isoazitine exerted antiparasitic activity on promastigotes and intracellular amastigotes of Leishmania infantum [57, 58],... 

The LD50S of songorine, napelline, and karakoline presented in Table 48.5 allow to conclude that C2o-diterpenoid alkaloids are among the least toxic alkaloids. 

Peese KM, Gin DY. Efficient synthetic access to the hetisine C2o-diterpenoid alkaloids. A concise synthesis of nominine via oxidoisoquinolinium-l,3-dipolar and dienamine-... 

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