Veatchine acetate

Veatchine acetate (210) was hydrolyzed to veatchine (1) in methanol at room temperature without using any external base (152). This unusual hydrolysis was explained by participation of methoxide ion which was formed by opening of the oxazolidine ring by methanol. Diterpenoid alkaloid derivatives lacking the oxazolidine ring, such as dihydroatisine diacetate (211) and veatchine azomethine acetate (10), failed to give compounds 212 and 78, respectively, in methanol under these conditions. 

Oxidation of veatchine (48) with Sarett reagent gave veatchinone (53), which, when reduced with NaBD4 in CH3OH, afforded an epimeric mixture of (54) and (55). This mixture was acetylated with acetic anhydride in pyridine and the acetates, (56) and (57), were separated by preparative-scale t.l.c. Treatment of (56) with 10% HC1 and re-acetylation gave (58). The 13C n.m.r. data indicated that there was no deuterium present at C-16 in (58) therefore, this rearrangement did not take place by a 15 —> 16 hydride shift. 

Recently, Pelletier, Nowacki, and Mody 155) reported that treatment of alkaloid imine derivatives with ethylene oxide in acetic acid or methanol afforded the oxazolidine ring-containing alkaloids in excellent yield. Treatment of lindheimerine (7) with ethylene oxide in acetic acid afforded ovatine (6) in 98% yield. Similarly, veatchine azomethine acetate (10) afforded veat-chine acetate (210) in 97% yield. Formation of the oxazolidine ring in these... 

Unlike ethylene oxide, oxetane reacted very slowly with the alkaloid imine derivatives to afford low yields of tetrahydro-l,3-oxazine derivatives. Treatment of veatchine azomethine acetate (10) with oxetane in acetic acid at 50° afforded the six-membered carbinolamine ether, homoveatchine acetate (220), in 25% yield. The latter was isolated as a mixture of C-20 epimers. 

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,... 

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. 

Michael reaction. The overall yield from (64) was 41 %. A similar synthetic route utilizing an acetal group (75) in place of the acetoxy-function was investigated. However, despite the fewer steps required, this sequence gave lower yields of the tricyclic ketone (74). This compound possesses the bcd ring system of the veatchine-type alkaloids. 

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). 

Degradation of the Oxazolidine Ring of C20 Diterpenoid Alkaloids.—A simple and efficient method for the degradation of the oxazolidine ring system has been developed. Treatment of veatchine (67) with acetic anhydride in pyridine, followed by complete removal of the excess pyridine and acetic anhydride, gave the diacetate (108). Without purification, this compound was refluxed in chloro-... 

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