Isoatisine

A. heterophyllum, in which atisine was the chief alkaloid, after standing four years, yielded 8 grams of isoatisine, due to isomerisation with heter-atisine. O 4 gm., and atisine hydrochloride, 0-35 gm. ... 

The isomerization of atisine to isoatisine and the conformational analysis of rings E and F of atisine, veatchine, and related alkaloids have been studied by n.m.r. spectroscopy. 12-O-Acetylnapelline is a new alkaloid which has been isolated from Aconitum karakolicum. 

The structure of atisinium chloride as 5 was confirmed recently by a single-crystal X-ray analysis (SO). The absolute configuration of atisinium chloride was determined as 45, 5S, 8/ , 10/ , 12/ , and 155 by Hamilton s method and confirmed by examination of sensitive Friedel pairs. A recent X-ray crystallographic study of isoatisine confirmed the assigned structure 75. The absolute configuration was established as 45, 55, 8/ , 10/ , 12/ , 155, and 195 for isoatisine. It is worth noting that isoatisine does not exist as a mixture of C-19 epimers. Early work on the chemistry of atisine and isoatisine... 

Dihydroatisine, a minor alkaloid of the roots of A. heterophyllum Wall, was isolated (SO) from the strong base fraction and its structure (78) was established by comparison with the sodium borohydride reduction product of atisine or isoatisine. Recently, an X-ray analysis of dihydroatisine confirmed (30) its structure and determined the absolute configuration as 45, 55, 87 , 107 , 127 , and 155. So far dihydroatisine has not been reported in any other plant. 

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. 

Refluxing ajaconine in methanol afforded a mixture from which a new compound identified (87) as 7a-hydroxyisoatisine (82) was isolated. The structure of the latter was established by 1H- and UC-NMR spectroscopy. When ajaconine was refluxed in CH3OD under nitrogen, a mixture of C-19, C-20-deuterated ajaconine (206) and C-19,C-20-deuterated 7 -hydroxy-isoatisine (207) was formed. Incorporation of deuterium in 206 and 207 indicated that ajaconine ionized and rearranged to 207 and that these species are in equilibrium in refluxing methanol. 

Among them five alkaloids and three flavonoid glycosides are known only from this plant while the rests are also reported from other plants. Gao et al. (2004) isolated and characterized six alkaloids (Figure 3) they are navirine (compound 1), isoatisine (2), hordenine (3), atisine (4), hetisinone (5) and delfissinol (6). Among them navirine (1) was reported as a new diterpenoid alkaloid while other five alkaloids are known in other plants too. Cao et al. (2008) reported two new C-20 alkaloids naviculine A (7) and B (8). Other terpenoid alkaloids were reported by our research group (Dall Acqua et al. 2008) they are navirine B (9), navirine C (10) and chellespontine (11). This latter one was previously isolated from aerial part of Consolida hellespontica (Desai et al., 1993). 

It is based on a comparison of the the well-known atisine-isoatisine transknowledge that ajaconine forms an salt with mineral acids rather than an salt. C-nmr-spectral studies on ajaconine hydrogen-bonding solvents the ether linkage... 

Additional evidence on this point is provided by the following sequence of reactions (22, 23). Isomerization of isoatisine (XXXI) with ethanolic hydrochloric acid gave a mixture of epimeric methyl ketones (XXXVIII, 1712 cm i). That skeletal rearrangement had not occurred during the isomerization was shown by borohydride reduction of XXXVIII to give... 

The Sarett oxidation of atisine and isoatisine affords the conjugated enones atisinone (XLIV) and isoatisinone (XLV), respectively (23). Refluxing XLIV in methanol or ethanol effects a smooth isomerization to XLV, a reaction which parallels the facile atisine isoatisine isomerization (see Section V, A). The Sarett oxidation of atisine and isoatisine also gave rise to neutral by-products of interest (23). From atisine was obtained a compound assigned structure XVLI on the basis of spectroscopic evidence [v ax (Nujol) 3289, 3195, 3077, 1704, 1629, 1658 cm i Ash (EtOH) 228 mp. (e 7800) t9.05, 3H singlet (C—CH3), t4.12 and 4.84, 2H doublets (J =2 cps, C=CH2), t3.95, IH multiplet (-Nfl CO-)] and by... 

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