Atisine acetate

Depending on the reaction time, treatment of atisine azomethine acetate (218) with ethylene oxide afforded either atisine acetate (219), atisine (4), or... 

Hexahydrobenzoyloxodedelphonine acetate (VI) was dehydrogenated by selenium at 330° and gave as chief product a hydrocarbon, b.p. 90°/0-02 mm., whose composition, ultra-violet absorption spectrum and chemical properties, so far as examined, indicate that it may be a bicyclopentenobenzene and therefore in a different category from the phenanthrene hydrocarbons yielded by the atisine group of bases. 

Treatment of the ketone (105) with methanolic KOH led to hydrolysis of the acetate group, retro-aldol reaction and aldol cyclization, which eventually afforded a mixture of epimeric alcohols (106) 33). This strategy was used to construct the basic skeletons of various alkaloids, e.g. talatisamine 34), atisine 35) and chasmanine36). 

Acetates, benzoates, tosylates, and mesylates exhibit analogous [l,2,3]-eliminations upon (gas phase) pyrolysis. Thus, Patchouli-acetate (104) reacts to 105 and 106 (52%, and 46%, resp.)65) and 57 yields 107 (low conversion) with migration of phenyl40). In the pyrolysis of bomyl benzoate (108) mainly (54 %) camphene (109)66) is formed, the atisine-derivative 110 (a or P) yields stereospecifically 111 (ot-epimer, 90 %) or 112 (P-epimer, 95 %)67), and the adamantane mesylate (113) yields the alkene 114 (38 %)68). 

A simple, efficient procedure for degrading the oxazolidine ring in C2o-diterpene bases has been discovered (Mody and Pelletier, Tetrahedron Letters, 1978, 3313). Veatchine (1), for example, with acetic anhydride-pyridine affords the diacetate (25), which on refluxing in chloroform yields (26) and 1,2-diacetoxyethane, by internal S y]2 attack. Atisine,... 

This c20 pyrophosphate (122), C20H36O7P2, is thought to provide the carbon framework of the diterpene alkaloids such as veatchine (123), atisine (124), and aconitine (125) (Fig. 5). It is not known at what stage the nitrogen is incorporated into the framework established by the skeleton. The potential for terpene rearrangements and the observation that the alkaloids are frequendy found esterified, often by acetic or benzoic acid, as well as free, has led to permutations and combinations producing over 100 such compounds. 

The atisine and Garrya (35,36) alkaloids have been interrelated by converting both atisine (XXX) and veatchine, by a parallel sequence of degradations, to the same A-acetyl ester (XCV) (35, 36). The respective azomethine acetates (LXXXVII, LXXXVIII) derived from atisine (12,16-bond) and veatchine (13,16-bond) were converted to the A-acetyl derivatives (LXXXIX, XC) by reduction, acetylation, and saponification. Oxidation of LXXXIX and CX with permanganate/periodate under controlled conditions gave the respective carboxylic acids (XCIa,... 

The azomethine (CXIV) derived from atisine undergoes a reaction of further interest when refluxed with zinc dust in acetic anhydride (28). The major product is the 0,V-diacetate (CXVIII) together with 5-10% of a bimolecular product to which structure CXIX is assigned. Saponification of CXIX affords the corresponding alcohol (CXX). The linkage between the halves of CXIX is believed to be at C-19, because of the severely hindered environment about C-20. 

Masamune 104) has also converted compound CCCXII, obtained from veatchine azomethine acetate, by a multistep procedure to the monoester carboxylic acid CCLIII. Since the latter has already been converted to atisine by Pelletier and Parthasarathy 96) this work completes in a formal sense the synthesis of atisine also. 

After the earlier work of Johnston and Overton, the alcohols (49) and (50) were obtained by borohydride reduction of (48), obtained from atisine. The a-alcohol (50) was purified by preparative t.l.c. and converted into the tosylate (51). On heating (51) with tetramethylguanidine in DMSO, an 85% yield of a mixture of isomers (52) and (53) was obtained. Compound (52) is identical with the product earlier prepared by pyrolytic rearrangement. Hydrogenation of (52) or (53) afforded the same dihydro-derivative. Deacetalization of (53) to the ketone (54) followed by reduction with lithium aluminium hydride afforded a mixture of the hydroxy-amines (55) and (56). These were treated with mercuric acetate to yield compounds (57) and (58). Jones oxidation of this epimeric mixture afforded compound (47). The structure of this compound was confirmed by an X-ray crystallographic analysis. 

A full report on the C n.m.r. studies of these and related compounds and a rebuttal of some of the previously published n.m.r. spectral interpretations (cf. this Report, 1978, Vol. 8, p. 238) have appeared. The rebuttal was submitted prior to the publication of the X-ray crystallographic studies. n.m.r. spectral data were reported for atisine (1), atisinone (68), isoatisine (66), isoatisinone (69), dihydroatisine (65), dihydroatisine diacetate (70), atidine (71), atidine diacetate (72), atisine azomethine (73), atisine azomethine acetate (74), atisine dihydro-azomethine (75), atisine A-methyl dihydro-azomethine (76), veatchine [(67a) and (67b)], garryine (77), dihydroveatchine (78), dihydroveatchine diacetate (79), veatchine azomethine (80), veatchine azomethine acetate (81), veatchine dihydro-azomethine (82), and veatchine X-methyl dihydro-azomethine (83). 

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