Atisanes

Atisane is the basic skeleton of various diterpene alkaloids (aconitum-alkaloids) found in the plant families of Ranunculaceae and Garryaceae. (-)-Atisine, as a typical representative, was isolated from the Atis plant Aconitum heterophyllum (Ranunculaceae), which also contains (-)-15,20-dihydroxy-16-atisen-19-oic acid as the lactone (19,20-olide). Erythroxylon monogynum and related speeies are reported to contain (-)-16-atisene. Euphorbiaceae such as Euphorbia acaulis and E. fidjiana produce (-)-16a,17-dihydroxyatisan-3-one. (+)-13-Atisene-16p,17-diol is known as serradiol due to its natural occurrence in Sideritis serrata (Labiatae). 

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Ghatak and co-workers49 have reported further progress on their synthetic elaboration of the atisane system, as outlined in Scheme 5. A key step in the synthesis of the tetracyclic compound (162) was the CuO-catalysed inter-molecular alkylation of the diazoacetyl compound (163). 

Plant products have also been detected in non-plant organisms. Morphine 1, the archetypal plant alkaloid, has in fact been shown to be a physiological plasma constituent and its production in mammals could be traced to the liver expression of the critical enzymes of its biosynthesis.17 In addition, the plant hormone abscisic acid 12 has been detected as an endogenous constituent of human brain,18 while caffeine 13 was isolated from a marine gorgonian (Paramuricea chamaelon)19 and the atisane diterpenoid serofendic acid 14, an inhibitor of the oxidant-induced mitochondrial death pathway and putative activator of mitoK(ATP) channels, has been characterised from foetal calf serum.20... 

OTt-3P,16a, 17-Trihydroxya tisane (atisane diterpene) Euphorbia quinquecostata (Euphorbiaceae) [stem wood] Inhibits PDB-R (PKC) binding... 

The major problem left in a formal total synthesis of the lycoctonine skeleton is the movement of the 8,15 double bond to the 7,8 position. W. A. Ayer and co-workers have also achieved an atisane to aconane rearrangement. 

The numbering system for the alkaloids used in this chapter is based upon the standard skeletons atisane, kaurane, and aconane and corresponds with the proposal suggested by J. W. Rowe and endorsed by O. E. Edwards, K. Wiesner, and the author. Thus the atisine, veatchine, and lycoctonine systems are numbered as in (1), (2), and (3), respectively.1... 

VI. The Chemistry of Alkaloids with a Modified Atisane Skeleton. 174... 

In recent years a wide range of Aconitum species native to Japan and India have been examined for alkaloids. Among those encountered are several which are modeled on an atisane skeleton but possess additional ring fusions. This section will. survey the chemistry of these interesting alkaloids. 

The nomenclature of these alkaloids is based upon the standard skeletons atisane, kaurane, and aconane with the numbering and stereochemistry illustrated. These skeletons have been incorporated into a proposal for the Common and Systematic Nomenclature of Cyclic Diterpenes which will be submitted to the lUPAC Commission on the Nomenclature of Organic Chemistry in 1969 and published in M. Fetizon and Le-Van-Thoi s forthcoming book on the cyclic diterpenes. 

From S. serrata (South-eastern Spain) several diterpenoids were obtained [49] the known lagascatriol (158), jativatriol (122), conchitriol (121), sideritol (143), and the new products serradiol (142) (an ent-atisane), benuol (119) and tobarrol (120) (both ent-beyeranes), lagascol... 

Again from Southern Spain, S. reverchonii contained derivatives of em-beyerane, ent-atisane, em-isopimarane [55] the new 12-acetyl-jativatriol (124), and the eight already known lagascol (157), lagascatriol... 

Moreover, this taxon is very similar to S. tragoriganum, because many products occur in both taxa. In total, seven enf-beyeranes and five ent-atisanes were identified [74-76] conchitriol (121), jativatriol (122), 1-acetyl-jativatriol (123), 12-acetyl-jativatriol (124), 1,12-diacetyl-jativatriol (125), 1,17-diacetyl-jativatriol (126), tobarrol (120), serradiol (142), isosideritol (146), 1-acetyl-sideritol (144), 1,17-diacetyl-sideritol (145) (new product), and atisideritol (147) (new product). 

S. granatensis, considered as an authentic taxa, contains [82] two ent-kauranes 18-acetyl-leucanthol (26) and 7,18-diacetyl-leucanthol (27) and the eni-atisane serradiol (142), but not ent-beyeranes. 

Another species from Canary Islands, S. ferrensis was veiy rich in diterpenoids [100]. Five new products were identified diacetyl-trachinodiol (155), ent-18-acetoxy-16a-hydroxy-atisane (148), and the ent-kauranes acetyl-candol A (3), acetyl-candol B (5), and ferrediol (39). Moreover, many known compounds occurred epicandicandiol (7), 7-acetyl-epicandicandiol (8), diacetyl-epicandicandiol (11), 18-palmitoyl-epicandicandiol (10), 7-acetyl-18-palmitoyl-epicandicandiol (12), candol A (2), candol B (4), 7-acetyl-trachinodiol (153), candidiol (20), candicandiol (6), episinfemal (45), em-kaur-16-ene (1). 

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