Atisine intermediate synthesis

Musso has reported the synthesis of diasterane (tricyclo-[3.1.1.I2 4]octane) 15. For this first member of the series of asteranes, the decarboxylation of 16b -> 16c was best achieved via the photolysis of the Barton ester of 16a in the presence of BuSH, as shown in Scheme 5.14 Fukumoto has accomplished asymmetric total synthesis of atisine 17, where the bridged pentacyclic intermediate 18, a precursor for atisine, was synthesized via an intramolecular double Michael reaction starting with 19, Scheme 6.15 Barton protocol was favored during the late stages of the synthesis and the presence of various functionalities was easily accommodated. 

The synthesis of the aromatic methyl ether (191) and the reduction of ring C has been studied." The backbone rearrangement of the synthetic intermediate (192) has been examined in the context of the synthesis of rearranged diterpenoids. The synthesis of the phenol (193), which is a degradation product of atisine, has been reported. 

C, Synthesis.—Atisine and Veatchine Types. Zalkow and co-workers developed syntheses of intermediates potentially transformable into atisine-type alkaloids, starting with podocarpic acid. The general approach is illustrated by a synthesis" of an ajaconine degradation product. Methyl O-methyl-7-keto-podocarpate (56) was reduced to the diol, which was converted by Birch reduction to dienone (57). The diene diol diacetate from this was converted to the 7,8-epoxide. Boron trifluoride converted this to the non-conjugated enone (58) which isomerised and... 

Addition of hydrogen cyanide. As one step in a total synthesis of effect conjugate addition of hydrogen cyanide to the intermediate... 

Synthesis of an Atisine-type Intermediate.—Two synthetic routes to the tricyclic dione (50) were explored by Beames and Mander.30 Using an approach analogous to one developed by Masamune,31 they converted l,2,3,4-tetrahydro-7-hydroxy-2-naphthoic acid (51) into the bromide (52). The reaction of the latter with t-butoxide produced a 3 1 mixture of the dienone ethers (54) and (55). The use of deblocking and oxidation reactions furnished the diketone (50). Reduction of (50) with borohydride furnished a 2 3 mixture of the alcohols (56) and (57). 

Hydrocarbon CXXXIV has also been synthesized by a similar sequence of reactions from abietic acid via maleopimaric acid (CXLI) by Zalkow and Girotra 44, 45). These authors have also converted CXLII, an intermediate obtained en route to hydrocarbon CXXXIV, to CXLIII, which possesses the complete carbocyclic skeleton of atisine in its correct relative configuration. Bell and Ireland had reported previously the synthesis of racemic CXLIII 46). 

A similar sequence 109) has been used for an atisine synthesis starting with the dZ-acid CCCXIVb. Conversion to the acyl azide CCCXXIIb was effected by treatment with ethyl chloroformate and triethylamine followed by sodium azide. Conversion of the acyl azide CCCXXIIb to the lactam CCCXXIIIb was effected via intermediates CCCXXIIIb-CCCXXVb as in the previously described Garrya sequence. This sequence constitutes a simple high-yield construction of the basic tetracyclic atisine skeleton (109). 

In 1974 Wiesner and his co-workers reported (96) the first formal total synthesis of talatisamine (68) starting from an atisine-type intermediate (242). A key step in this synthesis involved a rearrangement of the atisine skeleton to the aconitine-type skeleton, a reaction previously suggested... 

The Total Synthesis of Talatisamine.—The atisine-type intermediate (62) has been used in the synthesis of talatisamine (63).A key step in this synthetic route is the rearrangement of an atisine skeleton (structure B) to a lycoctonine skeleton (structure A). This type of rearrangement has been proposed in the biogenesis of alkaloids possessing the lycoctonine skeleton. Johnson and Overton S and Ayer and Deshpande have previously reported studies of this process. 

Several new synthetic approaches to the atisine and veatchine alkaloids have been reported, and a detailed account of the synthesis of an optically active relay intermediate in the synthesis of delphinine has appeared. 

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